Effects of dairy products on intestinal integrity in heat-stressed pigs.
Heat stress compromises intestinal integrity which may partially explain its negative effects on animal health and productivity. Research suggests that challenged intestinal barrier function improves with dietary dairy products in various models. Thus, the study objective was to evaluate the effects of bovine milk whey protein (WP) and colostral whey protein (CWP) on intestinal integrity in heat-stressed pigs. Crossbred gilts (39 ± 3 kg body weight) were fed 1 of 4 diets (n = 8 pigs/diet): control (Ct), control diet containing an 80% WP and 20% CWP product (WP80), control diet containing a 98% WP and 2% CWP product (WP98), and control diet containing a 100% WP product (WP100). After 7d on experimental diets, pigs were exposed to constant heat stress conditions (32 °C) for 24h. There were no treatment differences in growth or body temperature indices prior to heat stress. During heat exposure, both rectal temperature and respiration rate increased (+0.85 °C and 3-fold, respectively; P < 0.01), and feed intake and body weight decreased (44% and -0.5kg, respectively; P < 0.01), but neither variable was affected by dietary treatments. Plasma L-lactate and D-lactate concentrations increased (36%; P < 0.01) and tended to increase (19%; P = 0.09) with heat stress. After 24h of heat exposure, WP100-fed pigs had lower plasma D-lactate relative to Ct-fed pigs. Ileal transepithelial electrical resistance was decreased (37%; P = 0.02) in WP80 pigs, compared with controls. No differences were detected in other intestinal integrity ex vivo measurements. These data demonstrate that dietary WP and CWP did not mitigate intestinal integrity dysfunction during severe heat stress.


Effects of different light-curing units and obturation techniques on the seal of the Resilon/Epiphany system.
The purpose of this study was to compare the sealing ability of a resin- and polymer-based root canal obturation system (Resilon; Resilon Research LLC, Madison, CT/Epiphany; Clinical Technologies, Wallingford, CT) used in conjunction with different light-curing units and obturation techniques. A total of 120 decrowned single-rooted human teeth were used. After preparation of the root canals with 0.06 taper nickel-titanium rotary files to size 30, the roots were randomly assigned into three experimental groups according to the obturation technique used: (1) single cone, (2) cold lateral compaction, and (3) System B + Obtura. In all groups, the specimens were randomly assigned into four subgroups according to the polymerization method that was used to cure Epiphany sealer from the coronal aspect: (1) quartz-tungsten-halogen (QTH), (2) light-emitting diode (LED), (3) plasma-arc curing (PAC), and (4) chemical cure (uncured). Leakage was measured by the fluid-filtration method at 1 day and 1 week. Statistical analysis was performed by using Kruskal-Wallis and Wilcoxon signed-rank tests at p < 0.001. Fluid conductance of all groups increased significantly within time (p < 0.001). The tested obturation techniques had no significant effect on the leakage values (p = 0.433). The following statistical ranking was obtained for fluid-filtration values: uncured > PAC > LED > QTH (p < 0.001).


Acceptability and accuracy of saline infusion sonohysterography in women with postmenopausal bleeding.
To validate the diagnostic efficacy of saline infusion sonohysterography (SIS) in the evaluation of uterine cavity,in women with postmenopausal bleeding and endometrial thickness (3) 5 mm. Cross-sectional study. Military Hospital, Rawalpindi, from March 2005 to July 2008 and Combined Military Hospital, Multan, from September 2008 to June 2009. Seventy seven eligible participants included women complaining of postmenopausal bleeding were included; out of whom 69 completed the procedure satisfactorily. Pain scores during procedure were assessed to determine patient acceptability. Following saline infusion sonohysterography all patients also underwent an out door pipelle endometrial biopsy in a one-stop postmenopausal bleed clinic. Findings of sonohysterography were compared with hysteroscopy/hysterectomy specimen. Majority of the patients 34 (49.2%) experienced no pain during the procedure, 51 (74%) women had a positive SIS and the findings were negative in 18 (26%) patients. The commonest abnormal finding on SIS was focal thickening in 23 (32%) and endometrial polyp in 12 (17%) cases. Saline infusion hysterosonography picked up 3 cases of false positive polyps (5.8%) and missed a case of submucous fibroid near cervix (1.8%). Upon comparison of findings of hysteroscopy and hysterectomy in 53 cases, there was complete agreement in a total of 43 (88%) cases. The sensitivity of sonohysterography was 92% and specificity was 78%. All the ladies with abnormal SIS had diagnostic or therapeutic procedures and finally only 24 (35%) were managed on conservative follow-up. Normal SIS led to conservative management in 16 (88%). Sonohysterography in combination with endometrial biopsy is a useful technique useful for the evaluation of postmenopausal bleeding. Patient acceptability and diagnostic capability is high and it reduces demand for hysteroscopy.


Using QALYs in cancer: a review of the methodological limitations.
The objective of this paper is to examine how well the QALY captures the health gains generated by cancer treatments, with particular focus on the methods for constructing QALYs preferred by the UK National Institute for Health and Clinical Excellence (NICE). Data were obtained using a keyword search of the MEDLINE database and a hand search of articles written by leading researchers in the subject area (with follow up of the references in these articles). Key arguments were discussed and developed at an oncology workshop in September 2009 at the Office of Health Economics. Three key issues emerged. First, the EQ-5D, NICE's preferred measure of health-related quality of life (QOL) in adults, has been found to be relatively insensitive to changes in health status of cancer patients. Second, the time trade-off, NICE's preferred technique for estimating the values of health states, involves making assumptions that are likely to be violated in end-of-life scenarios. Third, the practice of using valuations of members of the general population, as recommended by NICE, is problematic because such individuals typically display a misunderstanding of what it is really like for patients to live with cancer. Because of the way in which it is constructed, the QALY shows important limitations in terms of its ability to accurately capture the value of the health gains deemed important by cancer patients. A research agenda for addressing these limitations is proposed.


Harnessing light with photonic nanowires: fundamentals and applications to quantum optics.
The efficient feeding of spontaneous emission (SE) into a controlled optical mode lies at the heart of a new generation of advanced optoelectronic devices, such as low-threshold microlasers and bright sources of quantum light. In the solid state, single-mode emission was first demonstrated by using the Purcell effect that arises in a resonant microcavity. Recently, the need to relax the constraints inherent to such a narrow-band approach has motivated large effort to develop structures ensuring broadband and efficient SE control. This minireview deals with fiber-like photonic nanowires, a class of high-index waveguides that features key assets in this context. Combining theoretical predictions and experimental results, the paper details the SE dynamics in such tiny wires. In addition, it shows how the far-field emission of a single wire can be tailored through proper engineering of the two wire ends. As an application in the field of quantum optics, we review the realization of an ultrabright single-photon source. This first device was based on a self-assembled quantum dot embedded in a wire antenna realized with a top-down fabrication process. Considering recent advances in the direct growth of tapered photonic wires, we also propose a bottom-up fabrication route to realize a complete device. In particular, this proposal ensures the optimal 3D positioning of a single emitter inside the antenna. Finally, future research and application prospects are also reviewed.


Intestinal calcium absorption is associated with bone mass in stone-forming women with idiopathic hypercalciuria.
Patients with idiopathic hypercalciuria are predisposed to osteoporosis despite their high enteral calcium absorption. Conversely, low calcium absorption has been reported in patients with osteoporosis. Because bone loss occurs earlier in women, this work explores the relationship between bone mineral density (BMD) and calcium absorption in premenopausal and postmenopausal hypercalciuric stone-forming women. BMD and intestinal calcium absorption were compared in 64 hypercalciuric and 42 normocalciuric calcium stone-forming women. Calcium absorption was assessed by using strontium as a surrogate marker for calcium. Strontium was administered to patients as an oral load, then measured in blood to calculate absorption after 60 minutes. Femoral and lumbar-spine BMD were measured by dual-energy x-ray absorptiometry. Strontium absorption was significantly increased in hypercalciuric stone formers, whereas BMD z score was decreased in hypercalciuric patients at the lumbar spine, but not the femur. The increase in strontium absorption was detected in both postmenopausal (n = 29) and premenopausal (n = 35) hypercalciuric patients. The decrease in lumbar-spine BMD was confirmed in postmenopausal, but not premenopausal, hypercalciuric patients. Strontium absorption was greater in hypercalciuric patients with a lumbar-spine BMD z score of -2 or less (n = 10) than in those with a score greater than -2 (n = 54). Multiple stepwise regression showed that lumbar-spine BMD was related negatively to intestinal strontium absorption and age in hypercalciuric patients. Results of the strontium absorption test suggest that the increase in calcium absorption is associated with a decrease in lumbar-spine BMD in hypercalciuric stone-forming women. Hypercalciuric stone-forming women with high calcium intestinal absorption denote a group of patients predisposed to loss of bone mass.


Development and validation of an optical biosensor for rapid monitoring of adalimumab in serum of patients with Crohn's disease.
Therapeutic drug monitoring of adalimumab is recommended to improve therapeutic outcome in patients with Crohn's disease. Performing an ELISA requires a rather long time-to-result and the necessity of collecting multiple samples to decrease the cost per adalimumab determination. In this study, we aim to develop and validate a rapid assay suitable for measuring a single adalimumab serum sample using a fiber-optic surface plasmon resonance (FO-SPR) based sensor. Therefore, we have immobilized MA-ADM28B8 as capture antibody on an FO-probe and conjugated MA-ADM40D8 as detecting antibody to gold nanoparticles. A dose-response curve ranging from 2.5 to 40 ng/mL adalimumab was obtained in 1/400 diluted serum. Serum samples of patients with adalimumab concentrations between 1 and 16 μg/mL were measured whereas the negative control, a sample spiked with infliximab at a concentration of 16 μg/mL, showed no significant signal. Using a pre-functionalized FO-probe, the technology requires less than 45 minutes for measuring a single sample. Comparison of measurements between the biosensor and the ELISA revealed an excellent agreement with a Pearson r coefficient of 0.99 and an intra-class coefficient of 0.99. The reduced assay time and the possibility of measuring a single sample are major advantages compared to the ELISA. The developed and validated optical adalimumab biosensor could be a valuable point-of-care diagnostic tool for adalimumab quantification in patients with Crohn's disease.


The medical science DMZ: a network design pattern for data-intensive medical science.
We describe a detailed solution for maintaining high-capacity, data-intensive network flows (eg, 10, 40, 100 Gbps+) in a scientific, medical context while still adhering to security and privacy laws and regulations. High-end networking, packet-filter firewalls, network intrusion-detection systems. We describe a "Medical Science DMZ" concept as an option for secure, high-volume transport of large, sensitive datasets between research institutions over national research networks, and give 3 detailed descriptions of implemented Medical Science DMZs. The exponentially increasing amounts of "omics" data, high-quality imaging, and other rapidly growing clinical datasets have resulted in the rise of biomedical research "Big Data." The storage, analysis, and network resources required to process these data and integrate them into patient diagnoses and treatments have grown to scales that strain the capabilities of academic health centers. Some data are not generated locally and cannot be sustained locally, and shared data repositories such as those provided by the National Library of Medicine, the National Cancer Institute, and international partners such as the European Bioinformatics Institute are rapidly growing. The ability to store and compute using these data must therefore be addressed by a combination of local, national, and industry resources that exchange large datasets. Maintaining data-intensive flows that comply with the Health Insurance Portability and Accountability Act (HIPAA) and other regulations presents a new challenge for biomedical research. We describe a strategy that marries performance and security by borrowing from and redefining the concept of a Science DMZ, a framework that is used in physical sciences and engineering research to manage high-capacity data flows. By implementing a Medical Science DMZ architecture, biomedical researchers can leverage the scale provided by high-performance computer and cloud storage facilities and national high-speed research networks while preserving privacy and meeting regulatory requirements.


Reconstruction of two-dimensional velocity distribution in scramjet by laser absorption spectroscopy tomography.
We propose a method to reconstruct the two-dimensional (2D) velocity distribution of flow fields by laser absorption spectroscopy tomography. A mathematic model is established to reveal the dependence of spectral absorbance on line-of-sight velocity distribution. Then, with multiple laser beams from different angular views covering the region of interest, a nonlinear equation set of 2D velocity distribution is established according to the model. The integrated absorbance coefficient distribution is reconstructed using the Landweber iteration algorithm and substituted into the nonlinear equation set for further simplification. Finally, the velocity distribution is reconstructed by solving the simplified equation group via the interior point algorithm. The proposed method is validated numerically by reconstructing the velocity distribution of water molecules, as calculated by computational fluid dynamics, over a cross section of a double-mode scramjet combustor. The method does not require adding extra tracer particles and avoids issues arising from the short lifetime of molecular tags. It is suitable for diagnosis of high-speed flow fields.


Ecological models and pesticide risk assessment: current modeling practice.
Ecological risk assessments of pesticides usually focus on risk at the level of individuals, and are carried out by comparing exposure and toxicological endpoints. However, in most cases the protection goal is populations rather than individuals. On the population level, effects of pesticides depend not only on exposure and toxicity, but also on factors such as life history characteristics, population structure, timing of application, presence of refuges in time and space, and landscape structure. Ecological models can integrate such factors and have the potential to become important tools for the prediction of population-level effects of exposure to pesticides, thus allowing extrapolations, for example, from laboratory to field. Indeed, a broad range of ecological models have been applied to chemical risk assessment in the scientific literature, but so far such models have only rarely been used to support regulatory risk assessments of pesticides. To better understand the reasons for this situation, the current modeling practice in this field was assessed in the present study. The scientific literature was searched for relevant models and assessed according to nine characteristics: model type, model complexity, toxicity measure, exposure pattern, other factors, taxonomic group, risk assessment endpoint, parameterization, and model evaluation. The present study found that, although most models were of a high scientific standard, many of them would need modification before they are suitable for regulatory risk assessments. The main shortcomings of currently available models in the context of regulatory pesticide risk assessments were identified. When ecological models are applied to regulatory risk assessments, we recommend reviewing these models according to the nine characteristics evaluated here.


Isolation of recombinant fragments of the major outer-membrane protein of Chlamydia trachomatis: their potential as subunit vaccines.
Recombinant fragments of the major outer-membrane protein (MOMP) of Chlamydia trachomatis, expressed at high levels in Escherichia coli, were isolated and purified. Antisera to the recombinant proteins reacted preferentially with overlapping synthetic peptides covering the immunoaccessible variable segments of MOMP. These sera also reacted in a species-specific manner with the surface of intact infectious elementary bodies, and in a Chlamydia genus-specific manner in assays using denatured or bound chlamydial antigens. The ability of recombinant MOMP preparations to elicit antibody to the surface of chlamydial elementary bodies raises the possibility that these proteins may be useful for chlamydial vaccine development.


Nitric oxide interacts with the retinoblastoma pathway to control eye development in Drosophila.
Animal organ development requires that tissue patterning and differentiation is tightly coordinated with cell multiplication and cell cycle progression. Several variations of the cell cycle program are used by Drosophila cells at different stages during development [1] [2]. In imaginal discs of developing larvae, cell cycle progression is controlled by a modified version of the well-characterized mammalian retinoblastoma (Rb) pathway [3] [4], which integrates signals from multiple effectors ranging from growth factors and receptors to small signaling molecules. Nitric oxide (NO), a multifunctional second messenger [5], can reversibly suppress DNA synthesis and cell division [6] [7]. In developing flies, the antiproliferative action of NO is essential for regulating the balance between cell proliferation and differentiation and, ultimately, the shape and size of adult structures in the fly [8] [9] [10]. The mechanisms of the antiproliferative activity of NO in developing organisms are not known, however. We used transgenic flies expressing the Drosophila nitric oxide synthase gene (dNOS1) and/or genes encoding components of the cell cycle regulatory pathways (the Rb-like protein RBF and the E2F transcription factor complex components dE2F and dDP) combined with NOS inhibitors to address this issue. We found that manipulations of endogenous or transgenic NOS activity during imaginal disc development can enhance or suppress the effects of RBF and E2F on development of the eye. Our data suggest a role for NO in the developing imaginal eye disc via interaction with the Rb pathway.


Extract from Aronia melanocarpa L. Berries Prevents Cadmium-Induced Oxidative Stress in the Liver: A Study in A Rat Model of Low-Level and Moderate Lifetime Human Exposure to this Toxic Metal.
The study investigated, in a rat model of low-level and moderate environmental exposure to cadmium (Cd; 1 or 5 mg Cd/kg diet, respectively, for 3 to 24 months), whether the co-administration of 0.1% extract from Aronia melanocarpa L. berries (AE) may protect against oxidative stress in the liver and in this way mediate this organ status. The intoxication with Cd, dose- and duration-dependently, weakened the enzymatic antioxidative barrier, decreased the concentrations of reduced glutathione and total thiol groups, and increased the concentrations of oxidized glutathione, hydrogen peroxide, xanthine oxidase, and myeloperoxidase in this organ. These resulted in a decrease in the total antioxidative status, increase in the total oxidative status and development of oxidative stress (increased oxidative stress index and malondialdehyde concentration) and histopathological changes in the liver. The administration of AE at both levels of Cd treatment significantly improved the enzymatic and nonenzymatic antioxidative barrier, decreased pro-oxidant concentration, and protected from the development of oxidative stress in the liver and changes in its morphology, as well as normalized the serum activities of liver enzymes markers. In conclusion, consumption of aronia products may prevent Cd-induced destroying the oxidative/antioxidative balance and development of oxidative stress in the liver protecting against this organ damage.


GPU-based 3D iceball modeling for fast cryoablation simulation and planning.
The elimination of abdominal tumors by percutaneous cryoablation has been shown to be an effective and less invasive alternative to open surgery. Cryoablation destroys malignant cells by freezing them with one or more cryoprobes inserted into the tumor through the skin. Alternating cycles of freezing and thawing produce an enveloping iceball that causes the tumor necrosis. Planning such a procedure is difficult and time-consuming, as it is necessary to plan the number and cryoprobe locations and predict the iceball shape which is also influenced by the presence of heating sources, e.g., major blood vessels and warm saline solution, injected to protect surrounding structures from the cold. This paper describes a method for fast GPU-based iceball modeling based on the simulation of thermal propagation in the tissue. Our algorithm solves the heat equation within a cube around the cryoprobes tips and accounts for the presence of heating sources around the iceball. Experimental results of two studies have been obtained: an ex vivo warm gel setup and simulation on five retrospective patient cases of kidney tumors cryoablation with various levels of complexity of the vascular structure and warm saline solution around the tumor tissue. The experiments have been conducted in various conditions of cube size and algorithm implementations. Results show that it is possible to obtain an accurate result within seconds. The promising results indicate that our method yields accurate iceball shape predictions in a short time and is suitable for surgical planning.


Molecular basis of the activation and dissociation of dimeric PYL2 receptor in abscisic acid signaling.
Phytohormone abscisic acid (ABA) is essential for plant responses to biotic and abiotic stresses. Dimeric receptors are a class of PYR1/PYL/RCAR (pyrabactin resistance 1/PYR1-like/regulatory component of ABA receptors) ABA receptors that are important for various ABA responses. While extensive experimental and computational studies have investigated these receptors, it remains not fully understood how ABA leads to their activation and dissociation for interaction with downstream protein phosphatase 2C (PP2C). Here, we study the activation and the homodimeric association processes of the PYL2 receptor as well as its heterodimeric association with protein phosphatase 2C 16 (HAB1) using molecular dynamics simulations. Free energy landscapes from ∼223 μs simulations show that dimerization substantially constrains PYL2 conformational plasticity and stabilizes the inactive state, resulting in lower ABA affinity. Also, we establish the thermodynamic model for competitive binding between homodimeric PYL2 association and heterodimeric PYL2-HAB1 association in the absence and presence of ABA. Our results suggest that the binding of ABA destabilizes the PYL2 complex and further stabilizes PYL2-HAB1 association, thereby promoting PYL2 dissociation. Overall, this study explains several key aspects on the activation of dimeric ABA receptors, which provide new avenues for selective regulation of these receptors.


Promoting information competency in biological psychology.
Information competency refers to skills that allow a student to identify appropriate sources of information, evaluate information critically, and use it ethically. Although the sudden increase of information available in electronic form has stimulated interest in information competency, the basic principles apply to all sources of information, including print. Information competency is especially critical in biological psychology. New discoveries in the neurosciences are featured every day by the mainstream media. As a society, we are being asked to make informed decisions about increasingly complex concepts, as in the case of the recent California proposition regarding stem cell research. Ideally, our students will become community leaders who will help shape these and other policy decisions, but the assumption of this role requires skills that extend long after the completion of a particular course or degree. Because of the perceived complexity of biological psychology, students new to the discipline may be reluctant to venture out into the experimental literature. A variety of activities are presented here that will build student confidence and shape information competency. Although these exercises can be used in a variety of disciplines, they are particularly well suited to biological psychology. The various exercises lend themselves to different levels of student expertise. Many of the exercises are quite appropriate for all levels and abilities, including graduate level students. As a bonus, these activities involve students in writing about biological psychology, providing a foundation for the writing of formal term papers or research reports.


Physiotherapy for cystic fibrosis in Australia: knowledge and acceptance of the Consensus Statement recommendations.
In 2008, a Consensus Statement was published with the aim of optimizing physiotherapy management for people with cystic fibrosis (CF) in Australia. The aim of this study was to measure knowledge and acceptance of the Consensus Statement recommendations. All physiotherapists providing treatment to people with CF in Australia were invited to complete a purpose-designed online survey to assess knowledge and uptake of key treatment recommendations. Sixty-eight physiotherapists took part (response rate 49%). Knowledge of treatment recommendations was high for airway clearance (94%) and exercise assessment (76%). Most respondents agreed with these recommendations (airway clearance 97% agreement, exercise 68% agreement). A small number of respondents (18%) correctly identified the current recommendation to segregate patients with different organisms during airway clearance, with most respondents (73%) implementing stricter infection control policies. Low levels of knowledge and agreement were evident for recommendations regarding measurement of blood sugar levels during exercise (36% knowledge and 28% agreement) and delivery of dornase alfa (53% and 65%). Physiotherapists from specialist CF centres were more likely to know the recommendations for blood sugar level measurement during exercise (P = 0.014), dornase alfa (P = 0.001) and non-invasive ventilation (P = 0.07) compared with physiotherapists in other settings. Physiotherapists are aware of treatment recommendations for CF in common areas of practice such as airway clearance and exercise. However, knowledge of recommendations is lower for specialized areas of practice and outside of CF centres. Strategies to improve awareness and uptake of the Consensus Statement among physiotherapists outside of CF centres are required.


The importance of program evaluation: how can it be applied to diverse genetics education settings?
The role of a genetic counselor often entails providing education to patient, community and/or health professional groups. While counseling supervision assists genetic counselors to be reflective about their clinical work and to enhance clinical skills, evaluation is a rather analogous process in the provision of education. Program evaluation of education activities can be applied to provide information about the needs of the target group (needs assessment), the delivery of the program (process evaluation) as well as determining the extent to which the education activity has met its intended aims (summative evaluation). Evaluation assists the educator to assess the impact of their program and provides an evidence base about genetics education. Although program evaluation can be a complex activity, the tools are ones that can be used by individuals to evaluate single or simple education activities. The components of evaluation are discussed with reference to genetic counseling practice and three very different examples of actual evaluations are provided to illustrate the diversity of evaluation strategy and programs to which it can be applied.


COVID-19 outcomes of patients with gynecologic cancer in New York City: An updated analysis from the initial surge of the pandemic.
Despite significant increase in COVID-19 publications, characterization of COVID-19 infection in patients with gynecologic cancer remains limited. Here we present an update of COVID-19 outcomes among people with gynecologic cancer in New York City (NYC) during the initial surge of severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]). Data were abstracted from gynecologic oncology patients with COVID-19 infection among 8 NYC area hospital systems between March and June 2020. Multivariable logistic regression was utilized to estimate associations between factors and COVID-19 related hospitalization and mortality. Of 193 patients with gynecologic cancer and COVID-19, the median age at diagnosis was 65.0 years (interquartile range (IQR), 53.0-73.0 years). One hundred six of the 193 patients (54.9%) required hospitalization; among the hospitalized patients, 13 (12.3%) required invasive mechanical ventilation, 39 (36.8%) required ICU admission. Half of the cohort (49.2%) had not received anti-cancer treatment prior to COVID-19 diagnosis. No patients requiring mechanical ventilation survived. Thirty-four of 193 (17.6%) patients died of COVID-19 complications. In multivariable analysis, hospitalization was associated with an age ≥ 65 years (odds ratio [OR] 2.12, 95% confidence interval [CI] 1.11, 4.07), Black race (OR 2.53, CI 1.24, 5.32), performance status ≥2 (OR 3.67, CI 1.25, 13.55) and ≥ 3 comorbidities (OR 2.00, CI 1.05, 3.84). Only former or current history of smoking (OR 2.75, CI 1.21, 6.22) was associated with death due to COVID-19 in multivariable analysis. Administration of cytotoxic chemotherapy within 90 days of COVID-19 diagnosis was not predictive of COVID-19 hospitalization (OR 0.83, CI 0.41, 1.68) or mortality (OR 1.56, CI 0.67, 3.53). The case fatality rate among patients with gynecologic malignancy with COVID-19 infection was 17.6%. Cancer-directed therapy was not associated with an increased risk of mortality related to COVID-19 infection.


[Role of nitric oxide in warm ischemia of the transplanted kidney].
Nitric oxide (NO) is a gas considered to have two roles: cytoprotective, derived from its vasodilating and anti-platelet aggregation effects, and cytotoxic, due to its free oxygen radical. It is produced by NO synthase; nitrites and nitrates are its end products. We investigated the role of NO in ischemia-perfusion injury. For the study, we utilized dogs weighing 15 to 25 kg. Autotransplantation of the left kidney and right nephrectomy were performed. Group I comprised 9 dogs submitted to renal autotransplantation; group II comprised 6 dogs submitted to renal autotransplantation after 24 h cold ischemia; group III comprised 6 dogs submitted to renal autotransplantation after 24 h cold ischemia and subsequent warm ischemia of 30 min; group IV comprised 9 dogs submitted to renal autotransplantation after 24 h cold ischemia and 60 min warm ischemia. A significant fall in nitrite levels was observed in dogs that had some type of surgical injury. Nitrate levels increased significantly in dogs that had warm ischemia. At 30 min reperfusion, a significant increase in the production of constitutive enzyme was observed in all groups. A significant increase in inducible enzyme at 30 min reperfusion was observed in the first three groups and no inducible enzyme was produced in the group that had more injury from ischemia (group IV). Nitrites are markers of the injury produced by surgery. Nitrates clearly express the injury to the organs caused by warm ischemia-reperfusion. The cNOS enzyme increases after surgery in response to surgical insult or stress. The iNOS enzyme increases in the kidneys that have suffered ischemia and are viable. Non-viable kidneys express no enzymatic activity (cNOS, iNOS).


Multilevel selection as Bayesian inference, major transitions in individuality as structure learning.
Complexity of life forms on the Earth has increased tremendously, primarily driven by subsequent evolutionary transitions in individuality, a mechanism in which units formerly being capable of independent replication combine to form higher-level evolutionary units. Although this process has been likened to the recursive combination of pre-adapted sub-solutions in the framework of learning theory, no general mathematical formalization of this analogy has been provided yet. Here we show, building on former results connecting replicator dynamics and Bayesian update, that (i) evolution of a hierarchical population under multilevel selection is equivalent to Bayesian inference in hierarchical Bayesian models and (ii) evolutionary transitions in individuality, driven by synergistic fitness interactions, is equivalent to learning the structure of hierarchical models via Bayesian model comparison. These correspondences support a learning theory-oriented narrative of evolutionary complexification: the complexity and depth of the hierarchical structure of individuality mirror the amount and complexity of data that have been integrated about the environment through the course of evolutionary history.


Profile of Escherichia coli O157:H7 pathogen responsible for hamburger-borne outbreak of hemorrhagic colitis and hemolytic uremic syndrome in Washington.
We analyzed Escherichia coli O157:H7 isolates from stool samples of five patients who had bloody diarrhea and were infected during a large food-borne outbreak of hemorrhagic colitis in Washington state. The isolates were assessed for Shiga-like toxin profile, adherence and plasmid traits, mouse virulence, capsule, and enterohemolysin production. The profiles of the five isolates were indistinguishable from each other and similar to that of E. coli O157:H7 strain EDL933, an organism responsible for a similar hamburger-associated food poisoning episode in 1982.


Differential medication overuse risk of novel anti-migraine therapeutics.
Medication overuse headache is estimated to affect 2% of the population, and is ranked in the top 20 most disabling disorders due to its high level of disability. Several therapies used in the treatment of acute migraine are thought to be associated with medication overuse headache, including opioids and triptans. With limited treatment options, it is critical to determine the risk profile of novel therapies prior to their widespread use. The current study explores the potential medication overuse risk of two novel therapeutic drug classes, namely the ditans: 5-HT1F receptor agonists, and the gepants: calcitonin gene-related peptide receptor antagonists, in a preclinical model of medication overuse. Persistent exposure of mice to the 5-HT1F agonist LY344864, but not olcegepant produced a significant reduction in hind paw and orofacial mechanical withdrawal thresholds as a surrogate readout of allodynia. In agreement, only LY344864 induced neuroplastic changes in trigeminal sensory afferents, increasing calcitonin gene-related peptide expression and basal trigeminal nociception. Our data highlight a differential medication overuse headache risk profile for the ditan and gepant classes of drugs that has important implications for their clinical use and patient education to help reduce the burden of medication overuse headache.


Experiences and Needs of African American Children and Adolescents in Supportive Care Roles for a Relative With Breast Cancer.
To explore the experiences and needs of African American (AA) children and adolescents who were identified by a cancer survivor in their family as providing substantial supportive care during diagnosis and treatment. 5 AA young adults who provided care and support to a family member with cancer when they were aged 7-19 years and 4 cancer survivors from a northeastern U.S. city. Focus groups and interviews were conducted, recorded, transcribed, and analyzed using content analysis until thematic saturation was reached. Themes focused on AA young supporters' lack of cancer-related information, reduced ability to communicate needs, and challenged views of themselves, relationships, faith, and the future at the time that they provided support. Nurses can support AA children and adolescents in caregiving roles by assessing their needs and providing information on diagnosis and treatment. In addition, nurses can conduct research on culturally adapted interventions that can better support AA children and adolescents caring for a parent or grandparent with cancer.


Elabela/Toddler Is an Endogenous Agonist of the Apelin APJ Receptor in the Adult Cardiovascular System, and Exogenous Administration of the Peptide Compensates for the Downregulation of Its Expression in Pulmonary Arterial Hypertension.
Elabela/toddler (ELA) is a critical cardiac developmental peptide that acts through the G-protein-coupled apelin receptor, despite lack of sequence similarity to the established ligand apelin. Our aim was to investigate the receptor pharmacology, expression pattern, and in vivo function of ELA peptides in the adult cardiovascular system, to seek evidence for alteration in pulmonary arterial hypertension (PAH) in which apelin signaling is downregulated, and to demonstrate attenuation of PAH severity with exogenous administration of ELA in a rat model. In silico docking analysis, competition binding experiments, and downstream assays were used to characterize ELA receptor binding in human heart and signaling in cells expressing the apelin receptor. ELA expression in human cardiovascular tissues and plasma was determined using real-time quantitative polymerase chain reaction, dual-labeling immunofluorescent staining, and immunoassays. Acute cardiac effects of ELA-32 and [Pyr1]apelin-13 were assessed by MRI and cardiac catheterization in anesthetized rats. Cardiopulmonary human and rat tissues from PAH patients and monocrotaline- and Sugen/hypoxia-exposed rats were used to show changes in ELA expression in PAH. The effect of ELA treatment on cardiopulmonary remodeling in PAH was investigated in the monocrotaline rat model. ELA competed for binding of apelin in human heart with overlap for the 2 peptides indicated by in silico modeling. ELA activated G-protein- and β-arrestin-dependent pathways. We detected ELA expression in human vascular endothelium and plasma. Comparable to apelin, ELA increased cardiac contractility, ejection fraction, and cardiac output and elicited vasodilatation in rat in vivo. ELA expression was reduced in cardiopulmonary tissues from PAH patients and PAH rat models, respectively. ELA treatment significantly attenuated elevation of right ventricular systolic pressure and right ventricular hypertrophy and pulmonary vascular remodeling in monocrotaline-exposed rats. These results show that ELA is an endogenous agonist of the human apelin receptor, exhibits a cardiovascular profile comparable to apelin, and is downregulated in human disease and rodent PAH models, and exogenous peptide can reduce the severity of cardiopulmonary remodeling and function in PAH in rats. This study provides additional proof of principle that an apelin receptor agonist may be of therapeutic use in PAH in humans.


Ecology of colors of firefly bioluminescence.
Dark-active North American fireflies emit green bioluminescence and dusk-active species emit yellow, in general. Yellow light and yellow visual spectral sensitivity may be adaptations to increase the signal-to-noise (that is, foliage-reflected ambient light) ratio for sexual signaling during twilight. The peaks of the electroretinogram visual spectral sensitivities of four species tested, two dark- and two dusk-active, correspond with the peak of their bioluminescent emissions.


Multicomponent Synthesis of Potentially Biologically Active Heterocycles Containing a Phosphonate or a Phosphine Oxide Moiety.
Several multicomponent synthetic approaches were elaborated for plenty of novel nitrogen or oxygen heterocycles containing a phosphonate or a phosphine oxide moiety. All multicomponent reactions were optimized through a model reaction in respect of the heating mode, molar ratio of the starting materials, atmosphere, catalyst, temperature, reaction time and solvent applied, and then, the extended preparation of small libraries of structurally-related compounds was performed. Most of the reactions could be considered as "green syntheses", as they were carried out in the absence of any catalyst and/or solvent using microwave (MW) irradiation or even at ambient temperature. The scaling-up of a MW-assisted synthesis was also elaborated in a continuous flow MW system. Altogether more than 150 heterocyclic organophosphorus compounds were synthesized, among them several derivatives showed moderate or promising activity against the HL-60 cell line and Bacillus subtilis bacteria.


Protein-based fluorescent nanoparticles for super-resolution STED imaging of live cells.
Development of nanoparticles for super-resolution imaging (sriNPs) can greatly enrich the toolbox of robust optical probes for biological studies. Moreover, sriNPs enable us to monitor the behavior of engineered nanomaterials in complex biological environments with high spatial resolution, which is important for advancing our understanding of nano-bio interactions. Up to now, reports on sriNPs have been scarce. In this work, we report a facile strategy to prepare protein-based fluorescent NPs that can be utilized as probes in super-resolution microscopy. The method is simple and straightforward, and easily extendible to other types of fluorophores. By using Atto647N-transferrin NPs as an example, we have achieved a roughly four-fold resolution improvement by using STED nanoscopy. These protein-based sriNPs possess excellent biocompatibility, good colloidal stability and photostability, making them attractive candidates for biological studies. Moreover, STED nanoscopy enables the precise imaging of NP structures in living cells, and revealed the co-existence of multiple NPs within one endosomal vesicle.


The THEMA study: a sociodemographic survey of hypercholesterolaemic individuals.
Hypercholesterolaemia is estimated to affect 20% of the population, although little sociodemographic information is available on affected individuals. The present study aimed to gather relevant information and investigate social determinants of dietary compliance. A telephone survey was carried out on a representative population sample. Quotas were applied for gender, geography and degree of urbanisation. Individuals were eligible if they were hypercholesterolaemic, and were being followed by a doctor. Sociodemographic, socioeconomic and health data were collected, as well as information about the individuals' perception of the disease, their relationship and beliefs surrounding food, and their food behaviour (shopping, cooking, eating-out, deviation from prescribed diet). The association between compliance with diet and medication was investigated. Overall, 802 individuals were included, representing 8% of those contacted, as opposed to the expected 20%. Mean (SD) age was 60 (14.2) years, with 51% of individuals living as a couple; 48% had a good level of physical activity; 44% considered that the hypercholesterolaemia was inherited; 31% felt that the disease was normal beyond the age of 45 years. The functional and convivial aspects of eating were of more importance than that of health maintenance. Cheese was particularly likely to be eaten in dietary lapses. Of a subgroup of 729 individuals, 476 (65%) took medication; of these 476 individuals, 51% complied with dietary recommendations (P < 0.05). The key factors associated with dietary compliance in hypercholesterolaemic individuals were identified: age, sex, the perceptions of hypercholesterolaemia, and the sociocultural aspects of food. By contrast to general assumptions, both dietary and medicinal measures are practised fairly well by a large proportion of these individuals.


A comparative study of automated blood pressure recorders.
Four automated blood pressure machines (Arteriosonde 1225, Bosomat 11D, Elag Koln BE 237R and Omron HEM 3) have been compared with each other and with the Hawksley Random Zero Sphygmomanometer in 18 subjects with a wide range of BP. Each form of measurement provided a high degree of internal consistency. The Arteriosonde 1225 consistently recorded systolic and diastolic pressures which were below the values obtained with the Random Zero instrument (P=0.001). The other 3 automated machines recorded BPs which did not differ significantly from the Random Zero or from each other. Heart rate readings did not differ significantly for any of the machines compared to manual recording. The disparity attributable to the Arterisonde could result from its being the only form of measurement to use an ultrasonic rather than a microphonic recording technique. However, the cheaper and more portable automated machines produce results which closely reflect those obtained by using a mercury sphygmomanometer.


A flexible genome-wide bootstrap method that accounts for ranking and threshold-selection bias in GWAS interpretation and replication study design.
The phenomenon known as the winner's curse is a form of selection bias that affects estimates of genetic association. In genome-wide association studies (GWAS) the bias is exacerbated by the use of stringent selection thresholds and ranking over hundreds of thousands of single nucleotide polymorphisms (SNPs). We develop an improved multi-locus bootstrap point estimate and confidence interval, which accounts for both ranking- and threshold-selection bias in the presence of genome-wide SNP linkage disequilibrium structure. The bootstrap method easily adapts to various study designs and alternative test statistics as well as complex SNP selection criteria. The latter is demonstrated by our application to the Wellcome Trust Case Control Consortium findings, in which the selection criterion was the minimum of the p-values for the additive and genotypic genetic effect models. In contrast, existing likelihood-based bias-reduced estimators account for the selection criterion applied to an SNP as if it were the only one tested, and so are more simple computationally, but do not address ranking across SNPs. Our simulation studies show that the bootstrap bias-reduced estimates are usually closer to the true genetic effect than the likelihood estimates and are less variable with a narrower confidence interval. Replication study sample size requirements computed from the bootstrap bias-reduced estimates are adequate 75-90 per cent of the time compared to 53-60 per cent of the time for the likelihood method. The bootstrap methods are implemented in a user-friendly package able to provide point and interval estimation for both binary and quantitative phenotypes in large-scale GWAS.


Evaluation of inciting causes, alternative targets, and risk factors associated with redirected aggression in cats.
To identify inciting causes, alternative targets, and risk factors associated with redirected aggression in cats. Case-control study. 19 cats with a history of redirected aggression and 64 cats with no such history. Medical records were reviewed to identify cats evaluated for problems with redirected aggression (case cats), in which the primary inciting stimulus and alternative target of aggression were clearly identifiable. Data obtained from the records and from follow-up interviews included details about the cats and incidents of redirected aggression. Owners of control cats were interviewed via telephone to obtain similar information on their cats. 22 incidents of redirected aggression were reported for the 19 case cats. In 95% of those incidents, loud noises or interactions with other cats were identified as the inciting stimuli. Case cats most commonly redirected their aggression toward the owner, followed by another cat living in the same household. Compared with control cats, case cats were more likely to have a sound phobia but were less likely to be outdoor cats. In addition, case cats were more likely to be from small households (<or= 2 people) than were control cats. In most situations, case cats had adopted a defensive body posture immediately before the incident of redirected aggression, which suggested that the underlying motivation was fear. Fear was likely the most common motivation for redirected aggression in the cats of this report. To reduce the risk of redirected aggression, veterinarians should encourage owners to socialize kittens and habituate them to novel objects and sounds.


Application of PAMPA-models to predict BBB permeability including efflux ratio, plasma protein binding and physicochemical parameters.
This study examines whether algorithms to predict brain penetration of 88 drug candidates could benefit from inclusion of PAMPA data such as Peff, flux and membrane retention. Specifically the ability to fit experimentally derived LogBB data with PAMPA information and compound related physicochemical and structural parameters was assessed. Collected data were analyzed by partial least square analysis and various regression models for LogBB. Four PAMPA methodologies were evaluated in this study including: (1) a PAMPA-BLM (black lipid membrane) model, (2) a PAMPA-DS (double sink) model, (3) a PAMPA-BBB (blood-brain barrier) model and (4) a PAMPA-BBB-UWL (unstirred water layer). Additionally, plasma protein binding (PPB) experiments and a Caco-2 assay were performed to determine the unbound fraction in plasma and the efflux ratio, respectively, for subsets of the selected compounds. This information was combined with the obtained PAMPA data in an effort to improve the predictions of LogBB. Taken in aggregate, the results presented, suggest that the PAMPA-BLM parameters are the most important contributors to predict the LogBB. The optimized multiple linear regression (MLR) relationship including the PAMPA-BLM properties demonstrated a slightly improved prediction compared to the model without the PAMPA-BLM parameters. Including the plasma protein binding of 15 compounds resulted in a significantly improved PAMPA-BLM prediction of LogBB, while integrating the efflux ratio with PAMPA-BLM or PAMPA-BBB Peff values, resulted in improved classification of brain permeable [BBB + (LogBB >or= 0)] and impermeable [BBB--(LogBB < 0)] compounds.


Experimental and theoretical studies of vacuum-ultraviolet electronic circular dichroism of hydroxy acids in aqueous solution.
The electronic circular dichroism (ECD) spectra of three L-hydroxy acids (L-lactic acid, (+)-(S)-2-hydroxy-3-methylbutyric acid, and (-)-(S)-2-hydroxyisocaproic acid) were measured down to 160 nm in aqueous solution using a vacuum-ultraviolet ECD spectrophotometer. To assign the two positive peaks around 210 and 175 nm and the one negative peak around 190 nm in the observed spectra, the ECD spectrum of L-lactic acid was calculated using time-dependent density functional theory (DFT) for the optimized structures by DFT and a continuum model. The observed ECD spectrum was successfully reproduced as the average spectrum for four optimized structures with seven water molecules that localized around the COO(-) and OH groups of L-lactic acid. The positive peak around 210 nm and the negative peak around 185 nm in the calculated spectrum were attributable to the nπ* transition of the carboxyl group, with the latter peak also being influenced by the ππ* transition of the carboxyl group; however, the positive peak around 165 nm involved unassignable higher energy transitions. The comparison of the calculated ECD spectra for L-lactic acid and L-alanine revealed that the network with loose hydrogen bonding around the COO(-) and OH groups is responsible for the flexible conformation of hydroxy acids and complicated side-chain dependence of ECD spectra relative to amino acids.


Pleistocene diversification in an ancient lineage: a role for glacial cycles in the evolutionary history of Dioon Lindl. (Zamiaceae).
Recent estimates of crown ages for cycad genera (Late Miocene) challenge us to consider what processes have produced the extant diversity of this ancient group in such relatively little time. Pleistocene climate change has driven major shifts in species distributions in Mexico and may have led to speciation in the genus Dioon by forcing populations to migrate up in elevation, thereby becoming separated by topography. We inferred orthologs from transcriptomes of five species and sequenced these in 42 individuals representing all Dioon species. From these data and published plastid sequences, we inferred dated species trees and lineage-specific diversification rates. Analyses of 84 newly sequenced nuclear orthologs and published plastid data confirm four major clades within Dioon, all of Pleistocene age. Gene tree analysis, divergence dates, and an increase in diversification rate support very recent and rapid divergence of extant taxa. This study confirms the Pleistocene age of Dioon species and implicates Pleistocene climate change and established topography in lineage spitting. These results add to our understanding of the cycads as evolutionarily dynamic lineages, not relicts or evolutionary dead ends. We also find that well-supported secondary calibration points can be reliable in the absence of fossils. Our hypothesis of lineage splitting mediated by habitat shifts may be applicable to other taxa that are restricted to elevation specific ecotones.


The Power of Predictive Model for Age and Sex Using Nasal Parameters.
Like languages, facial features have been linked to ethnicities. Basically, nasal index is ratio of nasal breadth to nasal length, which varies greatly among different anthropometric groups and climate regions. Aim: to investigate sexual dimorphic characterization in nasal parameters of the Ikwo population in South-east, Nigeria. The study recruited 250 Ikwo samples (males = 130, females = 120), after ethical approval gotten from University Research Committee and informed consents signed by the participants. Nasal length, width and indices were measured. Age and nasal indices appeared positively correlated but with weak R 2 Adjusted value (Age = 146 + 1.91 × Nasal indices, 35%). Also, sex and nasal indices were positive and very strong adjusted level (NI = 61+0.24 × Male and 61 + 0.084 × Female, and 82%). The mean nasal indices for both sexes in Ikwo population belong to platyrrhine nose classification, with predictive power that can be helpful in forensic science, craniofacial surgery, neurosurgery and developmental biology.


Mechanosensing during directed cell migration requires dynamic actin polymerization at focal adhesions.
The mechanical properties of a cell's microenvironment influence many aspects of cellular behavior, including cell migration. Durotaxis, the migration toward increasing matrix stiffness, has been implicated in processes ranging from development to cancer. During durotaxis, mechanical stimulation by matrix rigidity leads to directed migration. Studies suggest that cells sense mechanical stimuli, or mechanosense, through the acto-myosin cytoskeleton at focal adhesions (FAs); however, FA actin cytoskeletal remodeling and its role in mechanosensing are not fully understood. Here, we show that the Ena/VASP family member, Ena/VASP-like (EVL), polymerizes actin at FAs, which promotes cell-matrix adhesion and mechanosensing. Importantly, we show that EVL regulates mechanically directed motility, and that suppression of EVL expression impedes 3D durotactic invasion. We propose a model in which EVL-mediated actin polymerization at FAs promotes mechanosensing and durotaxis by maturing, and thus reinforcing, FAs. These findings establish dynamic FA actin polymerization as a central aspect of mechanosensing and identify EVL as a crucial regulator of this process.


Establishment and characterization of a panel of human lung cancer cell lines.
The establishment and characterization of 11 human lung cancer cell lines are described in this article. Nine of these cell lines were established over a 5-year period, from 1983 to 1988, from patients treated at the Kingston Regional Cancer Centre. These include eight definite or probable small cell lung cancer (SCLC) lines and one adenocarcinoma line. In addition, two other SCLC cell lines were characterized. All of the lines have been in continuous culture for more than 2 years. The clinical histories of the patients from whom the cell lines were derived are outlined here. Several features of the cell lines are presented, including the following: (1) a comparison of the histologic features of the cell lines with the original biopsy specimens; (2) the expression of various markers, including cytokeratin, carcinoembryonic antigen, calcitonin, and neuron-specific enolase; (3) activities of the enzymes l-dopa decarboxylase and the brain isoenzyme of creatine kinase; (4) growth characteristics; (5) cloning efficiency in soft agar; (6) tumorigenicity in nude mice; and (7) cytogenetic studies. These cell lines, obtained directly from patients with a spectrum of drug-sensitive and drug-resistant tumors, will be valuable in vitro models of sensitivity and resistance to chemotherapy in lung cancer.


MYC amplification as a prognostic marker of early-stage lung adenocarcinoma identified by whole genome copy number analysis.
Even in small-sized (≤ 2 cm in greatest dimension) and/or pathologic stage I lung adenocarcinoma (ADC), a considerable proportion of the patients will relapse within 5 years and show poor prognosis. The purpose of this study was to identify genetic alterations that define prognosis of patients with early-stage lung ADC. Regions of copy number alterations in 65 small-sized lung ADCs and 40 ADC cell lines were determined by using GeneChip Human Mapping 10-K and 250-K single-nucleotide polymorphism (SNP) arrays, respectively. A copy number assay based on real-time genomic PCR (RT-G-PCR) was done for 60 small-sized lung ADCs and 162 stage I lung ADCs. Several regions on chromosomes 5p, 7p, 8q, and 14q were frequently (>10%) amplified in both small-sized ADCs and lung ADC cell lines. In particular, the MYC gene was mapped in the minimum common region at chromosome 8q24.21, and therefore was indicated to be a target of gene amplification in lung ADCs. MYC amplification correlated with poor prognosis (P = 0.031) of patients with small-sized ADCs. MYC amplification detected by SNP array analysis was well reproduced by RT-G-PCR analysis. Therefore, to investigate the utility of MYC amplification as a prognostic marker for early-stage lung ADCs, 162 stage I lung ADCs were subjected to the analysis. MYC amplification was associated with relapse-free survival in these patients (P = 0.013 by multivariate Cox proportional hazard model analysis). These results strongly indicate that MYC amplification is a prognostic marker of patients with early-stage lung ADCs.


[Decrease in the immune response in old age and ways of restoring it].
A comparative age study of the immune response in females of CBA mice to the injection of ram erythrocytes has shown that the decreased level of response in old animals depends on the delayed involvement of T- and B-populations of lymphocytes in the process of antibody formation. The intensification of immune response in old animals is possible under the additional antigenic stimulation and introduction of syngenic bone marrow cells from intact mature animals.


Mitochondrial DNA replication during differentiation of murine embryonic stem cells.
Oxidative phosphorylation (OXPHOS), the intracellular process that generates the majority of the ATP of a cell through the electron-transfer chain, is highly dependent on proteins encoded by the mitochondrial genome (mtDNA). MtDNA replication is regulated by the nuclear-encoded mitochondrial transcription factor A (TFAM) and the mitochondrial-specific DNA polymerase gamma, which consists of a catalytic (POLG) and an accessory (POLG2) subunit. Differentiation of pluripotent embryonic stem cells (ESCs) into specific cell types requires expansion of discrete populations of mitochondria and mtDNA replication to meet the specific metabolic requirements of the cell. We determined by real-time PCR that expression of pluripotent markers is reduced before the upregulation of Polg, Polg2 and Tfam in spontaneously differentiating R1 murine (m)ESCs, along with transient increases in mtDNA copy number. In D3 mESCs, the initial transient increase did not take place. However, precursors of neuronal and cardiomyocyte differentiation were positive for both POLG and TFAM. Similar-stage ESCs also showed active mtDNA replication, identified by 5-bromo-2'-deoxy-uridine labelling, as mtDNA copy number increased. Retinoic-acid-induced differentiation resulted in more consistent patterns of replication and upregulation of Polg, Polg2 and Tfam, whereas siRNA knockdown demonstrated that steady-state expression of POLG is essential for maintaining pluripotency.


Autotransfusion in major orthopaedic surgery: experience with 1785 patients.
Using a prospective audit, we have evaluated the efficacy of an integrated autotransfusion regimen which comprised predepositing and intra- and postoperative blood salvage in major orthopaedic surgery. We examined prospectively the records of 1785 patients (1198 females, 5867 males, mean age 62 (range 16-90) yr, preoperative haemoglobin concentration 13.4 (SD 1.4) g dl-1) undergoing total hip arthroplasty (THA, 1229 patients), THA after removal of internal fixation devices (RFD + THA, 18 patients), total knee arthroplasty (TKA, 263 patients), revision surgery of the hip (HR cup + stem revision, 197 patients; cup revision, 53 patients; stem revision, 16 patients) and total knee revision (TKR, nine patients). We estimated that the number of predonations (MSBOS = maximum surgery blood order schedule) was 2 u. for THA, TKA and TKR, and 3 u. for partial or total hip revision and total hip arthroplasty with fixation removal. We found that it was possible to obtain the MSBOS in 1597 patients (89.5%). Homologous red blood cell (HRBC) transfusions were carried out in 131 patients (7.3%). We found that the need to use HRBC was significantly associated with failure to meet the number of MSBOS, female sex, lower preoperative haemoglobin concentration, use of calcium heparin for antithrombosis prophylaxis, more extensive surgery, higher ASA rating and co-existing diseases such as coronary artery disease.


The potential for climate-driven bathymetric range shifts: sustained temperature and pressure exposures on a marine ectotherm, Palaemonetes varians.
Range shifts are of great importance as a response for species facing climate change. In the light of current ocean-surface warming, many studies have focused on the capacity of marine ectotherms to shift their ranges latitudinally. Bathymetric range shifts offer an important alternative, and may be the sole option for species already at high latitudes or those within enclosed seas; yet relevant data are scant. Hydrostatic pressure (HP) and temperature have wide ranging effects on physiology, importantly acting in synergy thermodynamically, and therefore represent key environmental constraints to bathymetric migration. We present data on transcriptional regulation in a shallow-water marine crustacean (Palaemonetes varians) at atmospheric and high HP following 168-h exposures at three temperatures across the organisms' thermal scope, to establish the potential physiological limit to bathymetric migration by neritic fauna. We observe changes in gene expression indicative of cellular macromolecular damage, disturbances in metabolic pathways and a lack of acclimation after prolonged exposure to high HP. Importantly, these effects are ameliorated (less deleterious) at higher temperatures, and exacerbated at lower temperatures. These data, alongside previously published behavioural and heat-shock analyses, have important implications for our understanding of the potential for climate-driven bathymetric range shifts.


Flexible Mx specification of various extended twin kinship designs.
The extended twin kinship design allows the simultaneous testing of additive and nonadditive genetic, shared and individual-specific environmental factors, as well as sex differences in the expression of genes and environment in the presence of assortative mating and combined genetic and cultural transmission (Eaves et al., 1999). It also handles the contribution of these sources of variance to the (co)variation of multiple phenotypes. Keller et al. (2008) extended this comprehensive model for family resemblance to allow or a flexible specification of assortment and vertical transmission. As such, it provides a general framework which can easily be reduced to fit subsets of data such as twin-parent data, children-of-twins data, etc. A flexible Mx specification of this model that allows handling of these various designs is presented in detail and applied to data from the Virginia 30,000. Data on height, body mass index, smoking status, church attendance, and political affiliation were obtained from twins and their families. Results indicate that biases in the estimation of variance components depend both on the types of relative available for analysis, and on the underlying genetic and environmental architecture of the phenotype of interest.


Small cell variant of mantle cell lymphoma is an indolent lymphoma characterized by bone marrow involvement, splenomegaly, and a low Ki-67 index.
Mantle cell lymphoma (MCL) is recognized as a well-defined B cell neoplasm characterized by overexpression of cyclin D1 (CCND1), with "classical" and "aggressive" variant subtypes. A small-cell variant of MCL (small-MCL), resembling small lymphocytic lymphoma/chronic lymphocytic lymphoma (CLL/SLL), has been added to the World Health Organization classification. However, to the best of our knowledge, there have been no studies focusing on this neoplasm. In the present study, we analyzed 15 cases of CCND1-positive small-MCL, including immunohistochemical analysis of Ki-67 and CCND1 expression, and compared our findings with those of 151 cases of classical MCL. Morphologically, most small-MCL showed a diffuse growth pattern (76.9%), whereas others featured a very thin mantle zone pattern resembling a reactive follicle (23.1%). Bone marrow involvement and splenomegaly occurred significantly more frequently in small-MCL than in classical MCL (P < 0.05). Ki-67 expression in small-MCL was lower than in classical MCL (mean [± 2 SD] 12.5 ± 17.3% and 25.2 ± 25.5%, respectively; P < 0.001), but there was no significant difference in CCND1 expression (P = 0.2445). The 5-year survival rate in small-MCL was 83.3%. Although there was no significant difference in outcome between small-MCL and classical MCL (P = 0.287), only one small-MCL patient died of the disease. Thus, small-MCL constitutes a specific subset of indolent lymphoma with distinguishing features, possibly making a major contribution to the accuracy of therapeutic decisions. In addition, clinicians should be aware of the possible presence of small-MCL to avoid making a misdiagnosis of follicular hyperplasia or CLL/SLL.


UNC2025, a potent and orally bioavailable MER/FLT3 dual inhibitor.
We previously reported a potent small molecule Mer tyrosine kinase inhibitor UNC1062. However, its poor PK properties prevented further assessment in vivo. We report here the sequential modification of UNC1062 to address DMPK properties and yield a new potent and highly orally bioavailable Mer inhibitor, 11, capable of inhibiting Mer phosphorylation in vivo, following oral dosing as demonstrated by pharmaco-dynamic (PD) studies examining phospho-Mer in leukemic blasts from mouse bone marrow. Kinome profiling versus more than 300 kinases in vitro and cellular selectivity assessments demonstrate that 11 has similar subnanomolar activity against Flt3, an additional important target in acute myelogenous leukemia (AML), with pharmacologically useful selectivity versus other kinases examined.


Nil effects of μ-rhythm phase-dependent burst-rTMS on cortical excitability in humans: A resting-state EEG and TMS-EEG study.
Repetitive transcranial magnetic stimulation (rTMS) can induce excitability changes of a stimulated brain area through synaptic plasticity mechanisms. High-frequency (100 Hz) triplets of rTMS synchronized to the negative but not the positive peak of the ongoing sensorimotor μ-rhythm isolated with the concurrently acquired electroencephalography (EEG) resulted in a reproducible long-term potentiation like increase of motor evoked potential (MEP) amplitude, an index of corticospinal excitability (Zrenner et al. 2018, Brain Stimul 11:374-389). Here, we analyzed the EEG and TMS-EEG data from (Zrenner et al., 2018) to investigate the effects of μ-rhythm-phase-dependent burst-rTMS on EEG-based measures of cortical excitability. We used resting-state EEG to assess μ- and β-power in the motor cortex ipsi- and contralateral to the stimulation, and single-pulse TMS-evoked and induced EEG responses in the stimulated motor cortex. We found that μ-rhythm-phase-dependent burst-rTMS did not significantly change any of these EEG measures, despite the presence of a significant differential and reproducible effect on MEP amplitude. We conclude that EEG measures of cortical excitability do not reflect corticospinal excitability as measured by MEP amplitude. Most likely this is explained by the fact that rTMS induces complex changes at the molecular and synaptic level towards both excitation and inhibition that cannot be differentiated at the macroscopic level by EEG.


Direct visualization of sperm competition and sperm storage in Drosophila.
Drosophila females engage in multiple matings [1] [2] [3] [4] even though they can store sperm in specialized organs for most of their life [5]. The existence of sperm competition in Drosophila has been inferred from the proportion of progeny sired by the second male in double-mating experiments [6] [7] [8]. Investigators have used this approach to quantify genetic variation underlying sperm competition [8] [9] [10], to elucidate its genetic basis [11], to identify the dependence of different male competitive ability on the genotype of the females with which they mate [12] and to discern the potential role of sperm competition in species isolation [13] [14]. This approach assumes that the sperm from two males stored in a female compete to fertilize the eggs. The mechanism by which sperm competition is accomplished is still unknown, however. Here, fluorescence microscopy, cytometry, and differently labeled sperm were used to analyze the fate of sperm inside the female's sperm storage organs, to quantify sperm competition, and to assess how closely paternity success corresponds to the appearance and location of the sperm. The results show that the first male's sperm is retained for a shortened period if the female remates, and that the second males that sire more progeny either induce females to store and use more of their sperm or strongly displace resident sperm.


Accuracy of Fitbit Wristbands in Measuring Sleep Stage Transitions and the Effect of User-Specific Factors.
It has become possible for the new generation of consumer wristbands to classify sleep stages based on multisensory data. Several studies have validated the accuracy of one of the latest models, that is, Fitbit Charge 2, in measuring polysomnographic parameters, including total sleep time, wake time, sleep efficiency (SE), and the ratio of each sleep stage. Nevertheless, its accuracy in measuring sleep stage transitions remains unknown. This study aimed to examine the accuracy of Fitbit Charge 2 in measuring transition probabilities among wake, light sleep, deep sleep, and rapid eye movement (REM) sleep under free-living conditions. The secondary goal was to investigate the effect of user-specific factors, including demographic information and sleep pattern on measurement accuracy. A Fitbit Charge 2 and a medical device were used concurrently to measure a whole night's sleep in participants' homes. Sleep stage transition probabilities were derived from sleep hypnograms. Measurement errors were obtained by comparing the data obtained by Fitbit with those obtained by the medical device. Paired 2-tailed t test and Bland-Altman plots were used to examine the agreement of Fitbit to the medical device. Wilcoxon signed-rank test was performed to investigate the effect of user-specific factors. Sleep data were collected from 23 participants. Sleep stage transition probabilities measured by Fitbit Charge 2 significantly deviated from those measured by the medical device, except for the transition probability from deep sleep to wake, from light sleep to REM sleep, and the probability of staying in REM sleep. Bland-Altman plots demonstrated that systematic bias ranged from 0% to 60%. Fitbit had the tendency of overestimating the probability of staying in a sleep stage while underestimating the probability of transiting to another stage. SE>90% (P=.047) was associated with significant increase in measurement error. Pittsburgh sleep quality index (PSQI)<5 and wake after sleep onset (WASO)<30 min could be associated to significantly decreased or increased errors, depending on the outcome sleep metrics. Our analysis shows that Fitbit Charge 2 underestimated sleep stage transition dynamics compared with the medical device. Device accuracy may be significantly affected by perceived sleep quality (PSQI), WASO, and SE.


[Use of a cyclotron in the production of positron emitting radionuclides].
The experience acquired by our center during the first two years of using cyclotron 18/9 (IBA) dedicated to the production of clinical positron emission radionuclides is described. The cyclotron performance characteristics, production yields, quality control and synthesized radiotracers are analyzed. Cyclotron makes it possible to produce up to 3,300 mCi of 18F-, 270 mCi of 18F2, 3,100 mCi of 11C, 502 mCi of 13N (in 120, 60, 35 and 20 minutes respectively) and 540 mCi/min of 15O. In our center, about 85% of the PET studies are performed with 18F-FDG, whereas the remaining are done with 15O-water, 11C-bicarbonate, 11C-methionine, 13N-ammonia or 18F-. Cyclotron is included in the Radiopharmacy Unit of our PET facility and is subjected to a global quality control program. Follow-up of the bombardment parameters and periodic verifications of the cyclotron performance have made it possible to prevent equipment functioning problems, increase mean time between stoppage and decrease downtime. We conclude that cyclotron has high production capabilities and allows enough flexibility for a clinical and research positron emission tomography center; furthermore, it can also be used for regional distribution of 18F-FDG to satellite PET centers.


Evaluation of the current disease severity scores in paediatric FMF: is it necessary to develop a new one?
Modified adult disease severity scoring systems are being used for childhood FMF. We aim to test the clinical consistency of two common severity scoring systems and to evaluate the correlation of scores with the type of FMF mutations in paediatric FMF patients since certain mutations are prone to severe disease. Two hundred and fifty-eight children with FMF were cross-sectionally studied. Assessment of the disease severity was performed by using the modified scoring systems of Mor et al. and Pras et al. Genetic analysis was performed using PCR and restriction endonuclease digestion methods for the presence of 15 FMF gene mutations. FMF mutations were grouped into three based on well-known genotypic-phenotypic associations. Correlation between the mutation groups and the severity scoring systems was assessed. The consistency of the severity scoring systems was evaluated. The results of two scoring systems were not statistically consistent with each other (κ = 0.171). This inconsistency persisted even in a more homogeneous subgroup of patients with only homozygote mutations of M694V, M680I and M694I (κ = 0.125). There was no correlation between the mutation groups and either of the scoring systems (P = 0.002, r = 0,196 for scoring systems of Mor et al.; P = 0.009, r = 0.162 for Pras et al.). The inconsistency of the two scoring systems and lack of correlation between the scoring systems and mutation groups raises concerns about the reliability of these scoring systems in children. There is a need to develop a scoring system in children based on a prospective registry.


Chronic myelogenous leukemia and myeloproliferative disease.
In Section I, Dr. Stephen O'Brien reviews the latest data on the clinical use of imatinib (STI571, Gleevec, Glivec) in CML. His review focuses on the use of imatinib in newly diagnosed chronic phase patients and summarizes cytogenetic and molecular response data, as well as use of the agent at high doses and in combination with other drugs. A brief summary of the prospective international Phase III studies that are currently ongoing is also provided, and the issues of resistance and definition of suboptimal therapeutic response are also covered. Finally, therapeutic decision-making and treatment strategy are considered. In Section II, Dr. Ayalew Tefferi considers the latest developments in the biology and therapy of myeloid metaplasia/myelofibrosis. Dr. Tefferi covers what is currently understood of the biology of the disease and reviews established therapies for the condition as well as novel agents that are being used in clinical trials. The development of optimal management strategies for the disease is considered. In Section III, Dr. Peter Valent reviews the classification of mast cell proliferative disorders and covers the clinical and pathological presentation of this group of neoplasms. He reviews the state-of-the-art regarding the molecular biology of mastocytosis along with diagnostic criteria and novel treatment concepts.


Manufacturing Processes of Implantable Microelectrode Array for In Vivo Neural Electrophysiological Recordings and Stimulation: A State-Of-the-Art Review.
Electrophysiological recording and stimulation of neuron activities are important for us to understand the function and dysfunction of the nervous system. To record/stimulate neuron activities as voltage fluctuation extracellularly, microelectrode array (MEA) implants are a promising tool to provide high temporal and spatial resolution for neuroscience studies and medical treatments. The design configuration and recording capabilities of the MEAs have evolved dramatically since their invention and manufacturing process development has been a key driving force for such advancement. Over the past decade, since the White House Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative launched in 2013, advanced manufacturing processes have enabled advanced MEAs with increased channel count and density, access to more brain areas, more reliable chronic performance, as well as minimal invasiveness and tissue reaction. In this state-of-the-art review paper, three major types of electrophysiological recording MEAs widely used nowadays, namely, microwire-based, silicon-based, and flexible MEAs are introduced and discussed. Conventional design and manufacturing processes and materials used for each type are elaborated, followed by a review of further development and recent advances in manufacturing technologies and the enabling new designs and capabilities. The review concludes with a discussion on potential future directions of manufacturing process development to enable the long-term goal of large-scale high-density brain-wide chronic recordings in freely moving animals.


Local morphology predicts functional organization of experienced value signals in the human orbitofrontal cortex.
Experienced value representations within the human orbitofrontal cortex (OFC) are thought to be organized through an antero-posterior gradient corresponding to secondary versus primary rewards. Whether this gradient depends upon specific morphological features within this region, which displays considerable intersubject variability, remains unknown. To test the existence of such relationships, we performed a subject-by-subject analysis of fMRI data taking into account the local morphology of each individual. We tested 38 subjects engaged in a simple incentive delay task manipulating both monetary and visual erotic rewards, focusing on reward outcome (experienced value signal). The results showed reliable and dissociable primary (erotic) and secondary (monetary) experienced value signals at specific OFC sulci locations. More specifically, experienced value signal induced by monetary reward outcome was systematically located in the rostral portion of the medial orbital sulcus. Experienced value signal related to erotic reward outcome was located more posteriorly, that is, at the intersection between the caudal portion of the medial orbital sulcus and transverse orbital sulcus. Thus, the localizations of distinct experienced value signals can be predicted from the organization of the human orbitofrontal sulci. This study provides insights into the anatomo-functional parcellation of the anteroposterior OFC gradient observed for secondary versus primary rewards because there is a direct relationship between value signals at the time of reward outcome and unique OFC sulci locations.


Understanding the relationship between brain and upper limb function in children with unilateral motor impairments: A multimodal approach.
Atypical brain development and early brain injury have profound and long lasting impact on the development, skill acquisition, and subsequent independence of a child. Heterogeneity is present at the brain level and at the motor level; particularly with respect to phenomena of bilateral activation and mirrored movements (MMs). In this multiple case study we consider the feasibility of using several modalities to explore the relationship between brain structure and/or activity and hand function: Electroencephalography (EEG), both structural and functional Magnetic Resonance Imaging (sMRI, fMRI), diffusion tensor imaging (DTI), transcranial magnetic stimulation (TMS), Electromyography (EMG) and hand function assessments. 15 children with unilateral CP (ages: 9.4 ± 2.5 years) undertook hand function assessments and at least two additional neuroimaging and/or neurophysiological procedures: MRI/DTI/fMRI (n = 13), TMS (n = 11), and/or EEG/EMG (n = 8). During the fMRI scans and EEG measurements, a motor task was performed to study cortical motor control activity during simple hand movements. DTI tractography analysis was used to study the corpus-callosum (CC) and cortico-spinal tracts (CST). TMS was used to study cortico-spinal connectivity pattern. Type and range of severity of brain injury was evident across all levels of manual ability with the highest radiological scores corresponded to children poorer manual ability. Evidence of MMs was found in 7 children, mostly detected when moving the affected hand, and not necessarily corresponding to bilateral brain activation. When moving the affected hand, bilateral brain activation was seen in 6/11 children while 3/11 demonstrated unilateral activation in the contralateral hemisphere, and one child demonstrated motor activation predominantly in the supplementary motor area (SMA). TMS revealed three types of connectivity patterns from the cortex to the affected hand: a contralateral (n = 3), an ipsilateral (n = 4) and a mixed (n = 1) connectivity pattern; again without clear association with MMs. No differences were found between children with and without MMs in lesion scores, motor fMRI laterality indices, CST diffusivity values, and upper limb function. In the genu, midbody, and splenium of the CC, higher fractional anisotropy values were found in children with MMs compared to children without MMs. The EEG data indicated a stronger mu-restoration above the contralateral hemisphere in 6/8 children and above the ipsilateral hemisphere in 2/8 children. The current results demonstrate benefits from the use of different modalities when studying upper-limb function in children with CP; not least to accommodate to the variations in tolerance and feasibility of implementation of the differing methods. These exposed multiple individual brain-reorganization patterns corresponding to different functional motor abilities. Additional research is warranted to understand the transactional influences of early brain injury, neuroplasticity and developmental and environmental factors on hand function in order to develop targeted interventions.


[Appendicovesical fistula treated with elective laparoscopic surgery].
appendicovesical fistula is a rare complication of advanced acute appendicitis and represents a rare type of enterovesical fistula. Its symptoms are vague and imprecise and its diagnosis is difficult, requiring a high level of suspicion. Exploratory laparotomy has been the key for diagnosis and definitive treatment for many years, but recently the laparoscopic approach is standing out among different experienced groups as the method of choice. we report a new case of appendicovesical fistula in a 45 year old female, who was remitted from Urology with symptoms of persistent dysuria and pyuria. She was finally diagnosed by computerized tomography and the appendicovesical fistula was resolved by laparoscopic surgery. This case adds to the one hundred and fifteen cases published so far and to the four treated by the laparoscopic approach. conventional imaging methods are not reliable for the diagnosis of enterovesical fistula. Since most appendicovesical fistula are found to be secondary to non-diagnosed and advanced acute appendicitis in the majority of the consulted publications laparotomy is the key for the diagnosis of apendicovesical fistula. However laparoscopy is described as a diagnostic and therapeutic tool in few articles. We only found three articles in the literature referring to the laparoscopic approach as a therapeutic option. computerized tomography is the diagnostic method of choice when communication between the digestive tract and urinary tract is suspected, particularly if the suspected fistula is an appendicovesical one. The laparoscopic approach of an appendicovesical fistula is able to confirm the radiological diagnosis and provide a definitive treatment.


The evolution of stories: from mimesis to language, from fact to fiction.
Why a species as successful as Homo sapiens should spend so much time in fiction, in telling one another stories that neither side believes, at first seems an evolutionary riddle. Because of the advantages of tracking and recombining true information, capacities for event comprehension, memory, imagination, and communication evolved in a range of animal species-yet even chimpanzees cannot communicate beyond the here and now. By Homo erectus, our forebears had reached an increasing dependence on one another, not least in sharing information in mimetic, prelinguistic ways. As Daniel Dor shows, the pressure to pool ever more information, even beyond currently shared experience, led to the invention of language. Language in turn swiftly unlocked efficient forms of narrative, allowing early humans to learn much more about their kind than they could experience at first hand, so that they could cooperate and compete better through understanding one another more fully. This changed the payoff of sociality for individuals and groups. But true narrative was still limited to what had already happened. Once the strong existing predisposition to play combined with existing capacities for event comprehension, memory, imagination, language, and narrative, we could begin to invent fiction, and to explore the full range of human possibilities in concentrated, engaging, memorable forms. First language, then narrative, then fiction, created niches that altered selection pressures, and made us ever more deeply dependent on knowing more about our kind and our risks and opportunities than we could discover through direct experience. WIREs Cogn Sci 2018, 9:e1444. doi: 10.1002/wcs.1444 This article is categorized under: Cognitive Biology > Evolutionary Roots of Cognition Linguistics > Evolution of Language Neuroscience > Cognition.


Estimating parameters for generalized mass action models using constraint propagation.
As modern molecular biology moves towards the analysis of biological systems as opposed to their individual components, the need for appropriate mathematical and computational techniques for understanding the dynamics and structure of such systems is becoming more pressing. For example, the modeling of biochemical systems using ordinary differential equations (ODEs) based on high-throughput, time-dense profiles is becoming more common-place, which is necessitating the development of improved techniques to estimate model parameters from such data. Due to the high dimensionality of this estimation problem, straight-forward optimization strategies rarely produce correct parameter values, and hence current methods tend to utilize genetic/evolutionary algorithms to perform non-linear parameter fitting. Here, we describe a completely deterministic approach, which is based on interval analysis. This allows us to examine entire sets of parameters, and thus to exhaust the global search within a finite number of steps. In particular, we show how our method may be applied to a generic class of ODEs used for modeling biochemical systems called Generalized Mass Action Models (GMAs). In addition, we show that for GMAs our method is amenable to the technique in interval arithmetic called constraint propagation, which allows great improvement of its efficiency. To illustrate the applicability of our method we apply it to some networks of biochemical reactions appearing in the literature, showing in particular that, in addition to estimating system parameters in the absence of noise, our method may also be used to recover the topology of these networks.


Aortic arch abnormality in a patient with Klippel-Feil syndrome.
We present a case of a 43-year-old female with headaches, progressive paresthesias of the upper extremities, and vertigo. Ultrasonography could not visualize the left internal carotid artery (ICA). Magnetic resonance imaging (MRI) showed complete fusion of the C5, C6, and C7 levels, representing Klippel-Feil deformity. Angiography showed a unique abnormality of the aortic arch with complete absence of the left ICA. An embryologic defect associated with this type of abnormality is proposed, with defects of development of the third aortic arch and the aortic sac secondarily.


ANN Assisted-IoT Enabled COVID-19 Patient Monitoring.
COVID-19 is an extremely dangerous disease because of its highly infectious nature. In order to provide a quick and immediate identification of infection, a proper and immediate clinical support is needed. Researchers have proposed various Machine Learning and smart IoT based schemes for categorizing the COVID-19 patients. Artificial Neural Networks (ANN) that are inspired by the biological concept of neurons are generally used in various applications including healthcare systems. The ANN scheme provides a viable solution in the decision making process for managing the healthcare information. This manuscript endeavours to illustrate the applicability and suitability of ANN by categorizing the status of COVID-19 patients' health into infected (IN), uninfected (UI), exposed (EP) and susceptible (ST). In order to do so, Bayesian and back propagation algorithms have been used to generate the results. Further, viterbi algorithm is used to improve the accuracy of the proposed system. The proposed mechanism is validated over various accuracy and classification parameters against conventional Random Tree (RT), Fuzzy C Means (FCM) and REPTree (RPT) methods.


Attitudes toward genetic testing for cancer risk after genetic counseling and decision support: a qualitative comparison between hereditary cancer types.
This study aimed to qualitatively assess individuals' attitudes toward genetic testing for cancer risk after genetic counseling and decision support. As part of a larger study, 78 women considering genetic testing for hereditary breast/ovarian cancer (HBOC) risk and 22 individuals considering genetic testing for hereditary nonpolyposis colorectal cancer (HNPCC) completed an open-ended table of their perceived pros and cons of genetic testing. The most frequently reported pros were "to help manage my risk of developing cancer," "to help my family," and "to know my cancer risk." With regards to risk management, the HBOC group perceived genetic testing as most helpful in informing their general risk management practices, while the HN-PCC group focused on the potential to clarify their need for bowel cancer screening, suggesting that patients' perceptions of the benefits of genetic testing may differ across cancer syndromes. Individuals in both groups expressed concern about the potential psychological impact of genetic testing. We also found that some affected individuals may not fully comprehend the meaning of their potential test results. Eliciting patients' perceived pros and cons during genetic counseling is likely to be a valuable tool for improving patient care. This data also provides an improved evidence base for the development of patient education tools.


Long-term adherence to antiretroviral therapy in resource-limited settings: a bitter pill to swallow.
Adherence to antiretroviral therapy is an important predictor of long-term treatment success. Adherence can be differentiated between early adherence challenges, that are about integrating pill-taking into daily life, and long-term adherence, where patients struggle to maintain clinical connections and interrupt clinical care and medication use. In resource-limited settings, treatment interruptions may be more useful predictors of patient outcome than pill-taking alone. Interventions that are aimed at providing support to patients and their individual challenges to prevent interruptions in treatment and care may have a greater impact over time on clinically important outcomes than interventions targeted only at pill-taking behaviours.


"Test, Listen, Cure" (TLC) Hepatitis C Community Awareness Campaign.
Improved drugs have been approved for the treatment of hepatitis C virus (HCV), but many people are unaware of improved therapies that are now available to cure the illness in a high percentage of patients. The objectives of the Test, Listen, Cure (TLC) Hepatitis C Community Awareness Campaign include the development and implementation of a health education and promotion campaign in Memphis, Tennessee, and surrounding areas of western Tennessee, eastern Arkansas, and northern Mississippi, to increase community awareness about HCV, and to provide up-to-date provider education on HCV screening and treatment. The health education and promotion campaign, which will be conducted in collaboration with area hospitals, clinics, and nonprofit organizations, will provide information about how HCV infection is transmitted, risk factors for the disease, the importance of screening and treatment, and the availability of improved treatment for the disease. A second objective will be to provide continuing professional education on HCV screening and treatment to a minimum of 200 area health care providers, including primary care and internal medicine physicians and residents, physician assistants, nurse practitioners, providers who care for homeless persons, and dialysis unit nurses. Health education materials will be developed for this community awareness campaign that is culturally appropriate for African Americans and suitable for people with lower health literacy and educational attainment. Information will be compiled and disseminated about area providers who provide screening services and treatment for persons with HCV in order to facilitate linkages to care. Four focus groups of 8-10, African American adults aged 40-64, will be conducted to test the health education materials. The provider education on HCV will also address patient-physician communication and cultural competency. The National Medical Association regional chapters and expert physician consultants will provide assistance with delivering the education program. Results from this one year project will be available in early 2016. Depending on the availability of funding and successful implementation of the project, the TLC campaign will be extended to similar cities in the United States.