Molecular design based on receptor-independent pharmacophore: application to estrogen receptor ligands.
Estrogens, a group of steroid hormones, act primarily by regulating gene expression after binding with estrogen receptor (ER), a nuclear ligand-activated transcription factor, translocates to the nucleus after dimer formation, enhances the gene transcription. Estrogen Receptor Modulators (ERMs) have selective agonist and antagonist effects to different tissues, and the purpose of research on ERMs is to identify new potent and less toxic drug molecules. The present study has been focused on finding the structural requirements of ER ligand, using receptor-independent pharmacophore space modeling studies that can explore 3D structural features and configurations, responsible for the biological activity of structurally diverse compounds. The studies show (R=0.945, RMSD=2.186, Deltacost=677.354) the importance of hydrogen bond acceptors in the aromatic rings and a planner hydrophobic region in the molecular architecture along with critical geometrical distance between features are effectively crucial for binding with ER.


Experimental study of spatial coherence diffraction based on full-field coherence visualization.
A novel optical geometry for direct visualization of the optical coherence function is proposed. The diffractions of partially coherent light by apertures with various forms are experimentally investigated, and the full-field spatial coherence functions have been observed by using the proposed interferometric system. Similar to the well-known Airy disk stemming from optical diffraction, we studied the spatial coherence function near the coherence focal plane on the analogy of the Fraunhofer and Fresnel diffraction integrals. Following the conventional definitions for the optical resolutions in the optical imaging system, the lateral and longitudinal resolutions for spatial coherence imaging have been proposed.


Occupational therapists' awareness of guidelines for assessment and diagnosis of developmental coordination disorder: Mesure selon laquelle les ergothérapeutes connaissent les lignes directrices relatives à l'évaluation et au diagnostic du trouble du développement de la coordination.
Developmental coordination disorder (DCD) is a motor skills disorder that can have negative lifelong psychosocial impacts if not diagnosed. Occupational therapists have a role in facilitating a diagnosis for children with DCD through assessment. The purpose of this study was to determine the level of understanding of current DCD guidelines for assessment and diagnosis among occupational therapists working in paediatric settings in British Columbia, Canada. An online survey was e-mailed to occupational therapists who consented to be contacted for research purposes; 169 paediatric therapists responded. Data were reported using percentage, mean, and standard deviation of responses for each answer. Although many occupational therapists are aware of DCD and the diagnostic criteria, most are unaware of current guidelines for assessment and diagnosis. Many are using cutoff scores inconsistent with current recommendations and thus may not be facilitating a diagnosis when one may be appropriate. Occupational therapists may benefit from targeted education regarding DCD assessment and diagnosis.


A Review of Strongyloides spp. Environmental Sources Worldwide.
Strongyloides spp. are parasitic nematodes that are transmitted through the environment and are capable of causing disease. These nematodes affect an estimated 3-300 million humans worldwide. Identifying the environmental reservoirs of Strongyloides spp. is essential for the development of appropriate control strategies. This systematic literature review examined all published studies that identified Strongyloides stercoralis, Strongyloides fuelleborni, Strongyloides fuelleborni kellyi, and Strongyloides spp. from an environmental source. Most studies detected the nematode from dog and primate fecal samples. Other environmental sources identified were ruminants, cats, rodents, insects, water, soil, as well as fruit and vegetables. Most studies used microscopy-based identification techniques; however, several employed molecular-based techniques, which have become increasingly popular for the detection of Strongyloides spp. A limitation identified was a lack of studies that comprehensively screened all potential environmental samples in a region. Future research should undertake this holistic screening process to identify which environmental reservoirs pose the greatest significance to human health. Potential controls can be identified through the identification of environmental sources. Understanding where Strongyloides spp. is commonly found within the environment of endemic areas will inform environmental control strategies to reduce this neglected disease.


Two-phase flow visualization under reservoir conditions for highly heterogeneous conglomerate rock: A core-scale study for geologic carbon storage.
Geologic storage of carbon dioxide (CO2) is considered a viable strategy for significantly reducing anthropogenic CO2 emissions into the atmosphere; however, understanding the flow mechanisms in various geological formations is essential for safe storage using this technique. This study presents, for the first time, a two-phase (CO2 and brine) flow visualization under reservoir conditions (10 MPa, 50 °C) for a highly heterogeneous conglomerate core obtained from a real CO2 storage site. Rock heterogeneity and the porosity variation characteristics were evaluated using X-ray computed tomography (CT). Multiphase flow tests with an in-situ imaging technology revealed three distinct CO2 saturation distributions (from homogeneous to non-uniform) dependent on compositional complexity. Dense discontinuity networks within clasts provided well-connected pathways for CO2 flow, potentially helping to reduce overpressure. Two flow tests, one under capillary-dominated conditions and the other in a transition regime between the capillary and viscous limits, indicated that greater injection rates (potential causes of reservoir overpressure) could be significantly reduced without substantially altering the total stored CO2 mass. Finally, the capillary storage capacity of the reservoir was calculated. Capacity ranged between 0.5 and 4.5%, depending on the initial CO2 saturation.


Recent progress in the discovery of selective, non-peptide ligands of somatostatin receptors.
Over the past 5 years, researchers in industry and academia have reported the design, synthesis and evaluation of many non-peptide ligands for somatostatin receptors. Structurally diverse agonists and antagonists that, in some cases, exhibit selectivity among the somatostatin receptor subtypes have been published. These agents represent research tools for the clarification of individual receptor pharmacology and are also promising leads for the development of orally active therapeutics for endocrine disorders, proliferative diseases and mood disorders. This review summarizes recent developments in the identification of non-peptide ligands of somatostatin receptors.


Ultrastructure and capsule of Mycoplasma meleagridis.
The ultrastructural study of Mycoplasma meleagridis utilized the electron microscope techniques of sectioning, histochemical staining, critical-point drying, and freeze etching. The predominant morphotype was a spherical form ranging in diameter from 200 to 700 nm. The other morphotypes were dumbbell-shaped cells interconnected by membranous tubules, and chains of streptococcal-like cells. These forms suggest replication by binary fission. An extracellular structure in the form of a capsular matrix was observed by staining with ruthenium red and potassium tellurite, and was also seen in specimens prepared by critical-point drying and freeze etching.


An audit of laparoscopic surgeries in Ile-Ife, Nigeria.
After several years of lagging behind due to several constraints, many general surgeons across Nigeria are now performing laparoscopic surgery. An audit of the procedure in our setting is required. To describe the outcome of consecutive laparoscopic general surgical procedures performed at the Obafemi Awolowo University Teaching Hospital, South-western Nigeria. All patients with general surgical conditions who had laparoscopic surgery from January 2009 through May 2010 in our hospital were prospectively studied and type of pre, intra and postoperative data including sex, age, indication for surgery, and outcome of the procedure were obtained and analysed. Sixty-two patients (ages 18 to 72 years) had laparoscopic surgeries within the study period. Eighteen (29%) patients had laparoscopic cholecystectomy, 13 (21%) had laparoscopic appendicectomy, 10 (16.1%) had laparoscopic adhesiolysis, 7 (11.3%) laparoscopic biopsies of intraabdominal masses while 14(22.6%) others had diagnostic laparoscopies for a range of suspected abdominal conditions. All diagnostic procedures were performed as day cases while the duration of hospital stay was one to two days for the therapeutic procedures. Two(3%) procedures, including a biopsy of hepatic mass and a cholecystectomy were converted to open surgery due to significant haemorrhage. A minor bile duct injury was recorded in one patient who had cholecystectomy and superficial port site wound infections were noticed in two patients who had appendectomy. No mortality was recorded. Our results show the feasibility of laparoscopic surgery in Nigeria. We advocate local adaptation and improvisations to increase the use of laparoscopic surgery in Nigerian hospitals.


Identification of candidates for PFO closure in the echocardiography laboratory.
A patent foramen ovale (PFO) is implicated in several pathologic processes, including that of cryptogenic stroke (cCVA). Recent trials identify "high-risk" PFOs in patients with cCVA as likely to benefit from percutaneous closure. The younger the patient (<60 years old) the more likely a PFO may be attributable to the cCVA. The RoPE Score index helps determine the likelihood that an existing PFO is related to a cCVA. This may help guide the clinician and patient when contemplating percutaneous PFO closure. When evaluating a patient for possible percutaneous closure, one should identify the CVA as a typical ischemic type stroke. In order to "rule-out" other causes of CVA, imaging of the intracranial arteries, cervical, and aortic arch vessels should be performed. Small vessel disease or a lacunar-type infarct should be excluded. To rule out atrial fibrillation, prolonged monitoring should be performed. An index has been developed to determine the probability that a PFO is the causative etiology and calculates the risk of recurrence. This may help guide the clinician and patient in the decision for PFO closure. In addition, one should consider a work-up for a hypercoagulable state. We will obtain an ultrasound of the lower extremities or consider deep pelvic vein thrombosis (prolonged sitting or malignancy). If the closure is to be performed, the Food and Drug Administration (FDA) has approved the Amplatzer PFO Occluder and the GORE Cardioform Septal Occluder for percutaneous closure. These devices are both approved in patients predominately between ages 18 and 60 years with a cCVA due to presumed paradoxical embolism as verified by a neurologist and cardiologist and when other causes of ischemic CVA have been excluded. "High-risk" PFOs appear to achieve the most potential benefit from percutaneous closure.


Self-assembly of Gd3+/SDS/HEPES complex and curcumin entrapment for enhanced stability, fluorescence image in cellular system.
At present, strategies to disperse hydrophobic molecules in water without altering their chemical structures include conventional surfactant-based micellar and vesicular systems, encapsulation into water dispersible polymeric nanoparticles, and loading onto the surface of various metal nanoparticles. Here, we report a simple and low cost platform to incorporate hydrophobic molecules into a stable water dispersible nanostructure that can significantly increase the stability of the encapsulated materials. The platform is based on the incorporation of hydrophobic molecules into the self-assembled complex of gadolinium ion (Gd3+), sodium dodecyl sulfate (SDS), and 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) called GdSH. After being incorporated, the two model hydrophobic dyes, curcumin and curcumin borondifluoride show approximately 50% and 30% improved stability, respectively. Investigation of the self-assembled 10-14 multilayered 60nm spheres with inter-layer distances of 4.25nm indicates coordination of SDS and HEPES with Gd3+. Incorporation of the hydrophobic molecules into the multilayered spheres results in reduction of the interlayer distance of the multilayer spheres to 4.17nm, suggesting enhanced packing of the hydrophobic chain of SDS and HEPES around the Gd3+. The incorporation of the two curcuminoids into the self-assembled complex also causes an increase in fluorescence quantum yield of the two dyes, thus suggesting spatial confinement of the packed dye molecules. The better cellular uptake of the nanoparticles is responsible for the expected enhancement in fluorescence image of the encapsulated materials.


Performance of a fully automated in vitro allergy testing system.
Since the development of the radioallergosorbent test (RAST) for quantification of allergen-specific IgE, numerous non-radoisotopic methods have been devised which combine the proven cellulose disc technology with enzyme-linked immunoassay methods. The HY.TEC EIA (Hycor Biomedical, Inc. Irvine, CA) was compared with Pharmacia CAP with respect to overall system features and assay performance characteristics. The HY.TEC EIA and Pharmacia CAP were compared with respect to calibrator range, sensitivity, type of detection, type of solid phase, throughput, and mode of operation. To determine the assay sensitivity and specificity for a variety of allergens, a total of 2,447 tests were performed on both CAP and HY.TEC EIA. The samples were scored positive in both cases using a cutoff of 0.35 IU/mL. The general features of the HY.TEC EIA system are comparable to Pharmacia UniCAP, with the added advantage of higher throughput. Intra-assay precision was 7% and inter-assay precision was 9-15%. Using CAP as a comparative method, HY.TEC EIA has a sensitivity of 94.0% and a specificity of 94.4%. The HY.TEC EIA demonstrates excellent agreement with the Pharmacia CAP system in the determination of allergen-specific IgE. With the automation necessary in today's clinical laboratory, we conclude that the HY.TEC EIA is a state-of-the-art tool for the diagnosis of allergic disease.


Loss of polarity regulators initiates gasdermin-E-mediated pyroptosis in syncytiotrophoblasts.
The syncytiotrophoblast is a human epithelial cell that is bathed in maternal blood on the maternal-facing surface of the human placenta. It therefore acts as a barrier and exchange interface between the mother and fetus. Syncytiotrophoblast dysfunction is a feature of pregnancy pathologies, like preeclampsia. Dysfunctional syncytiotrophoblasts display a loss of microvilli, which is a marker of aberrant apical-basal polarization, but little data exist about the regulation of syncytiotrophoblast polarity. Atypical PKC isoforms are conserved polarity regulators. Thus, we hypothesized that aPKC isoforms regulate syncytiotrophoblast polarity. Using human placental explant culture and primary trophoblasts, we found that loss of aPKC activity or expression induces syncytiotrophoblast gasdermin-E-dependent pyroptosis, a form of programmed necrosis. We also establish that TNF-α induces an isoform-specific decrease in aPKC expression and gasdermin-E-dependent pyroptosis. Therefore, aPKCs are homeostatic regulators of the syncytiotrophoblast function and a pathogenically relevant pro-inflammatory cytokine leads to the induction of programmed necrosis at the maternal-fetal interface. Hence, our results have important implications for the pathobiology of placental disorders like preeclampsia.


Secondary closure of alveolar cleft with resorbable collagen membrane and a combination of intraoral autogenous bone graft and deproteinized anorganic bovine bone.
Secondary alveolar bone grafting is a method that enables an excellent oral rehabilitation of the patients having alveolar cleft. The aim of this work is to report the closure of the alveolar cleft with the use of harvested autogenous bone graft combined with deproteinized anorganic bovine bone (Bio-Oss) under local anesthesia. Nine patients with age range, 8-11 years were consulted for their unilateral alveolar cleft. A combination of symphyseal bone and deproteinized bovine bone mineral (DBBM) was placed into the alveolar cleft defect. Clinical and radiographical assessments were performed at 1, 3, and 6 months postoperatively. The healing period was uneventful in all cases, and no complications, such as membrane exposure, infection, or harvest site morbidity, were observed. All treated defect sites exhibited excellent bone formation, with an average of 5.45 mm (range, 2-9 mm; standard deviation 1.93 mm) of augmentation achieved overall. The treatment of vertically deficient alveolar ridges with guided bone regeneration using a mixture of autogenous bone and DBBM and resorbable collagen membrane can be considered successful, using this technique in an out-patient office setting.


Italian Rett database and biobank.
Rett syndrome is the second most common cause of severe mental retardation in females, with an incidence of approximately 1 out of 10,000 live female births. In addition to the classic form, a number of Rett variants have been described. MECP2 gene mutations are responsible for about 90% of classic cases and for a lower percentage of variant cases. Recently, CDKL5 mutations have been identified in the early onset seizures variant and other atypical Rett patients. While the high percentage of MECP2 mutations in classic patients supports the hypothesis of a single disease gene, the low frequency of mutated variant cases suggests genetic heterogeneity. Since 1998, we have performed clinical evaluation and molecular analysis of a large number of Italian Rett patients. The Italian Rett Syndrome (RTT) database has been developed to share data and samples of our RTT collection with the scientific community (http://www.biobank.unisi.it). This is the first RTT database that has been connected with a biobank. It allows the user to immediately visualize the list of available RTT samples and, using the "Search by" tool, to rapidly select those with specific clinical and molecular features. By contacting bank curators, users can request the samples of interest for their studies. This database encourages collaboration projects with clinicians and researchers from around the world and provides important resources that will help to better define the pathogenic mechanisms underlying Rett syndrome.


Developing aspect of carbon coils formation during the beginning stage of the process.
Carbon coils could be synthesized using C2H2/H2 as source gases and SF6 as an incorporated additive gas under thermal chemical vapor deposition system. The surface morphologies of samples were investigated step by step during the beginning stage of the process. After finishing the substrate temperature set to 750 degrees C, the formation of circular-type nickel clusters were observed in places. By setting the total pressure to 100 Torr, most of the circular-type clusters were disappeared, whereas a few number of big-sized circular-type clusters having several micrometer-sized diameters were infrequently observed. After 0.5 minutes deposition reaction, carbon nanofilaments could be observed on a specific point of the sample. Further deposition reaction gave rise to the increase in the density of carbon nanofilaments as a form of two similar shaped carbon nanofilaments sticked together. After 10 minutes deposition reaction, the nanosized wave-like carbon coils was formed first and then the formation of the microsized carbon coils would be initiated from the nanosized wave-like carbon coils.


Strain-induced self-assembly of crystallites in elastomers.
We propose a model of strain-induced crystallization in elastomers, combining Flory's original work with a description of crystallization adopted from the theory of micellar solutions. The experimentally observed hysteresis appears in the model due to a continuous, unidirectional change of the free energy difference between straightened polymer sections which occur isolated and those which are aggregated. The model yields good qualitative and even semiquantitative agreement with measurements of crystallization in natural rubber at variable cross-link density, strain amplitude, and temperature. The attendant description of the stress hysteresis is less good but still qualitatively correct.


Specific issues in clinical trials on the use of barrier membranes in periodontal regeneration.
There are presently a number of different barriers available for use clinically in guided tissue regeneration (GTR) procedures. A number of trials using these techniques and comparing different types of barrier membranes are being published in the scientific literature. This review discusses issues related to clinical trials on the use of barrier membranes in periodontal regeneration. Outcome measures, both clinical and histological, are discussed in relation to results following GTR procedures. The difference between regeneration and repair is reviewed as well as methods of clinical and histologic assessment of both these outcomes. Data regarding the impact of patient variables and tooth or defect variables on outcomes are presented and suggestions for study designs are made based on these variables. Aspects of assessing for an appropriate sample size in superiority and equivalency trials using GTR techniques are presented as well as interpretation of results following these trials and their clinical significance.


Better understanding the utilization of damage control laparotomy: A multi-institutional quality improvement project.
Rates of damage control laparotomy (DCL) vary widely and consensus on appropriate indications does not exist. The purposes of this multicenter quality improvement (QI) project were to decrease the use of DCL and to identify indications where consensus exists. In 2016, six US Level I trauma centers performed a yearlong, QI project utilizing a single QI tool: audit and feedback. Each emergent trauma laparotomy was prospectively reviewed. Damage control laparotomy cases were adjudicated based on the majority vote of faculty members as being appropriate or potentially, in retrospect, safe for definitive laparotomy. The rate of DCL for 2 years prior (2014 and 2015) was retrospectively collected and used as a control. To account for secular trends of DCL, interrupted time series was used to effectiveness of the QI interventions. Eight hundred seventy-two emergent laparotomies were performed: 73% definitive laparotomies, 24% DCLs, and 3% intraoperative deaths. Of the 209 DCLs, 162 (78%) were voted appropriate, and 47 (22%) were voted to have been potentially safe for definitive laparotomy. Rates of DCL ranged from 16% to 34%. Common indications for DCL for which consensus existed were packing (103/115 [90%] appropriate) and hemodynamic instability (33/40 [83%] appropriate). The only common indication for which primary closure at the initial laparotomy could have been safely performed was avoiding a planned second look (16/32 [50%] appropriate). A single faceted QI intervention failed to decrease the rate of DCL at six US Level I trauma centers. However, opportunities for improvement in safely decreasing the rate of DCL were present. Second look laparotomy appears to lack consensus as an indication for DCL and may represent a target to decrease the rate of DCL after injury. Epidemiological study with one negative criterion, level III.


Wearable Technologies for Electrodermal and Cardiac Activity Measurements: A Comparison between Fitbit Sense, Empatica E4 and Shimmer GSR3.
The capability of measuring specific neurophysiological and autonomic parameters plays a crucial role in the objective evaluation of a human's mental and emotional states. These human aspects are commonly known in the scientific literature to be involved in a wide range of processes, such as stress and arousal. These aspects represent a relevant factor especially in real and operational environments. Neurophysiological autonomic parameters, such as Electrodermal Activity (EDA) and Photoplethysmographic data (PPG), have been usually investigated through research-graded devices, therefore resulting in a high degree of invasiveness, which could negatively interfere with the monitored user's activity. For such a reason, in the last decade, recent consumer-grade wearable devices, usually designed for fitness-tracking purposes, are receiving increasing attention from the scientific community, and are characterized by a higher comfort, ease of use and, therefore, by a higher compatibility with daily-life environments. The present preliminary study was aimed at assessing the reliability of a consumer wearable device, i.e., the Fitbit Sense, with respect to a research-graded wearable, i.e., the Empatica E4 wristband, and a laboratory device, i.e., the Shimmer GSR3+. EDA and PPG data were collected among 12 participants while they performed multiple resting conditions. The results demonstrated that the EDA- and PPG-derived features computed through the wearable and research devices were positively and significantly correlated, while the reliability of the consumer device was significantly lower.


Suppression of microRNA-155 exerts an anti-inflammatory effect on CD4+ T cell-mediated inflammatory response in the pathogenesis of atherosclerosis.
In the current study, we aimed to investigate the effects of miR-155 on CD4+ T cell-mediated immune response in the pathogenesis of atherosclerosis. CD34+ hematopoietic stem cells, CD4+ T lymphocytes, endothelial cells (ECs), and vascular smooth muscle cells (VSMCs) were harvested from the same donor. Knockdown of miR-155 in the CD4+ T cells was achieved by lentiviral transfection, whereas control RNA-transfected or untransfected lymphocytes were used as controls. The transfected CD4+ T cells were activated by incubating with oxidized low-density lipoprotein-treated dendritic cells. The proliferative capacities, phenotype distribution, and cytokine secretion profiles of the activated CD4+ T cells from different groups were evaluated. The activated lymphocytes were used to treat ECs co-cultivated with VSMCs. The ability of the CD4+ T cells to induce the apoptosis of the ECs and to promote the proliferation of the VSMCs was investigated. Inhibition of miR-155 was found to significantly reduce the proliferation rate of the transfected CD4+ T cells. CD4+ T lymphocytes transfected with the miR-155 inhibitor showed increased populations of T helper type 2 and regulatory T cells, as well as more production of anti-inflammatory cytokines. MiR-155 knockdown was also shown to significantly hamper the ability to CD4+ T cells to induce EC apoptosis and to promote the growth of VSMCs. Our data suggested that inhibition of miR-155 in CD4+ T cells could slow down the formation of atherosclerotic plaques. These results lay the groundwork for future research on the therapeutic potential of miR-155 against atherosclerosis-associated cardiovascular diseases.


The transcriptome of the entomopathogenic fungus Culicinomyces clavisporus contains an ortholog of the insecticidal ribotoxin Hirsutellin.
The entomopathogenic fungus Culicinomyces clavisporus is known to infect and kill mosquito larvae and therefore has been seen as a potential biological control agent against disease vector mosquitoes. Whereas most fungal entomopathogens infect hosts by penetrating the external cuticle, C. clavisporus initiates infection through ingestion (per os). This unique infection strategy suggests that the C. clavisporus genome may be mined for novel pathogenicity factors with potential for vector control. To this end, an Isoseq-based transcriptome analysis was initiated, and resulted in a total of 3,512,145 sequences, with an average length of 1,732 bp. Transcripts assembly and annotation suggested that the C. clavisporus transcriptome lacked the cuticle-degrading proteins that have been associated with other entomopathogenic fungi, supporting the per os pathogenicity process. Furthermore, mining of the sequence data unexpectedly revealed C. clavisporus transcripts homologous to the Hirsutellin toxin. Comparative sequence analyses indicated that the C. clavisporus Hirsutellin predicted protein has retained the canonical molecular features that have been associated with the ribotoxic and insecticidal properties of the original toxin isolated from Hirsutella thompsonii. The identification of an Hirsutellin ortholog in C. clavisporus was supported by phylogenetic analyses demonstrating that Culicinomyces and Hirsutella were closely related genera in the Ophiocordycipitaceae family. Validation of the mosquitocidal activity of this novel C. clavisporus protein has yet to be performed but may help position Hirsutellin orthologs as prime candidates for the development of alternative biocontrol approaches complementing the current toolbox of vector mosquito management strategies.


First record of Aedes (Stegomyia) albopictus in Belgium.
The 1st record of Aedes albopictus in Belgium was made in a village in Oost-Vlaanderen Province. Two preimaginal stages were collected on October 31, 2000, in the used tire stock of a recycling company that imports tires from the USA and Japan. The species has reproduced on site, and local environmental conditions make its establishment possible. Anopheles plumbeus was a common companion species found in tires in high densities.


RFX transcription factors are essential for hearing in mice.
Sensorineural hearing loss is a common and currently irreversible disorder, because mammalian hair cells (HCs) do not regenerate and current stem cell and gene delivery protocols result only in immature HC-like cells. Importantly, although the transcriptional regulators of embryonic HC development have been described, little is known about the postnatal regulators of maturating HCs. Here we apply a cell type-specific functional genomic analysis to the transcriptomes of auditory and vestibular sensory epithelia from early postnatal mice. We identify RFX transcription factors as essential and evolutionarily conserved regulators of the HC-specific transcriptomes, and detect Rfx1,2,3,5 and 7 in the developing HCs. To understand the role of RFX in hearing, we generate Rfx1/3 conditional knockout mice. We show that these mice are deaf secondary to rapid loss of initially well-formed outer HCs. These data identify an essential role for RFX in hearing and survival of the terminally differentiating outer HCs.


Passing current through touching molecules.
The charge flow from a single C(60) molecule to another one has been probed. The conformation and electronic states of both molecules on the contacting electrodes have been characterized using a cryogenic scanning tunneling microscope. While the contact conductance of a single molecule between two Cu electrodes can vary up to a factor of 3 depending on electrode geometry, the conductance of the C(60)-C(60) contact is consistently lower by 2 orders of magnitude. First-principles transport calculations reproduce the experimental results, allow a determination of the actual C(60)-C(60) distances, and identify the essential role of the intermolecular link in bi- and trimolecular chains.


NH4HCO3 gas-generating liposomal nanoparticle for photoacoustic imaging in breast cancer.
In this study, we have developed a biodegradable nanomaterial for photoacoustic imaging (PAI). Its biodegradation products can be fully eliminated from a living organism. It is a gas-generating nanoparticle of liposome-encapsulating ammonium bicarbonate (NH4HCO3) solution, which is safe, effective, inexpensive, and free of side effects. When lasers irradiate these nanoparticles, NH4HCO3 decomposes to produce CO2, which can absorb much of the light energy under laser irradiation with a specific wavelength, and then expand under heat to generate a thermal acoustic wave. An acoustic detector can detect this wave and show it as a photoacoustic signal on a display screen. The intensity of the photoacoustic signal is enhanced corresponding to an increase in time, concentration, and temperature. During in vivo testing, nanoparticles were injected into tumor-bearing nude mice through the caudal vein, and photoacoustic signals were detected from the tumor, reaching a peak in 4 h, and then gradually disappearing. There was no damage to the skin or subcutaneous tissue from laser radiation. Our developed gas-generating nanomaterial, NH4HCO3 nanomaterial, is feasible, effective, safe, and inexpensive. Therefore, it is a promising material to be used in clinical PAI.


Second stimulation in the same ovarian cycle: an option to fully-personalize the treatment in poor prognosis patients undergoing PGT-A.
Our primary objective was to assess whether immediately undergoing a second stimulation in the same ovarian cycle (DuoStim) for advanced-maternal-age and/or poor-ovarian-reserve (AMA/POR) patients obtaining ≤ 3 blastocysts for preimplantation-genetic-testing-for-aneuploidies (PGT-A) is more efficient than the conventional-approach. All AMA/POR patients obtaining ≤ 3 blastocysts after conventional-stimulation between 2017 and 2019 were proposed DuoStim, and 143 couples accepted (DuoStim-group) and were matched for the main confounders to 143 couples who did not accept (conventional-group). GnRH-antagonist protocol with recombinant-gonadotrophins and agonist trigger, intra-cytoplasmatic-sperm-injection (ICSI) with ejaculated sperm, PGT-A and vitrified-warmed euploid single-blastocyst-transfer(s) were performed. The primary outcome was the cumulative-live-birth-delivery-rate per intention-to-treat (CLBdR per ITT) within 1 year. If not delivering, the conventional-group had 1 year to undergo another conventional-stimulation. A cost-effectiveness analysis was also conducted. The CLBdR was 10.5% in the conventional-group after the first attempt. Only 12 of the 128 non-pregnant patients returned (165 ± 95 days later; drop-out = 116/128,90.6%), and 3 delivered. Thus, the 1-year CLBdR was 12.6% (N = 18/143). In the DuoStim-group, the CLBdR was 24.5% (N = 35/143; p = 0.01), 2 women delivered twice and 13 patients have other euploid blastocysts after a LB (0 and 2 in the conventional-group). DuoStim resulted in an incremental-cost-effectiveness-ratio of 23,303€. DuoStim was costlier and more effective in 98.7% of the 1000 pseudo-replicates generated through bootstrapping, and the cost-effectiveness acceptability curves unveiled that DuoStim would be more cost-effective than the conventional-approach at a willingness-to-pay threshold of 23,100€. During PGT-A treatments in AMA/POR women, DuoStim can be suggested in progress to rescue poor blastocyst yields after conventional-stimulation. It might indeed prevent drop-out or further aging between attempts.


Occupational health nursing as a component of baccalaureate nursing education.
Much can be gained by the nursing profession and by society by having well-prepared, professional occupational health nurses. Furthermore, conceptual knowledge about occupational health will better prepare the non-specialized nurse for her or his nursing practice. Lastly, knowledge about the hazards and risks that may accompany one's occupation will increase the nurse's awareness of the hazards that she/he may face in her/his own occupational setting. For these reasons the incorporation of occupational health content in the baccalaureate nursing programs would be a singular achievement for the nursing profession. It is clear that work-related injuries and illnesses pose a major challenge to today's health care providers. Most occupational health problems are preventable. It is fitting and indeed imperative that members of the nursing profession be leaders in a concerted effort to reduce the many risks in the workplace. The U.S. Public Health Service (1983) states that it is their goal that "by 1990 at least 70% of primary health care providers should routinely elicit occupational health exposures as part of the patient (health) history and should know how to interpret the information in an understandable manner." It is only through the introduction of important occupational health concepts in baccalaureate schools of education that this goal will be accomplished. Knowledge about occupational health nursing is fragmented. Furthermore, an occupational health curriculum, when it does exist, is varied in its content and its emphasis. this stems in part from a dearth of knowledge and experience by educators in the field of occupational health.(ABSTRACT TRUNCATED AT 250 WORDS)


Realization of Quantum Secure Direct Communication with Continuous Variable.
With the progress of theoretical and applied technologies, the communication system based on the classical encryption is seriously threatened by quantum computing and distributed computing. A communication method that directly loads confidential information on the quantum state, quantum secure direct communication (QSDC), came into being for resisting security threats. Here, we report the first continuous-variable QSDC (CV-QSDC) experimental demonstration for verifying the feasibility and effectiveness of the CV-QSDC protocol based on Gaussian mapping and propose a parameter estimation for signal classification under the actual channels. In our experiment, we provided 4 × 102 blocks, where each block contains 105 data for direct information transmission. For the transmission distance of 5 km in our experiment, the excess noise is 0.0035 SNU, where SNU represents the unit of shot-noise units. The 4.08 × 105 bit per second experimental results firmly demonstrated the feasibility of CV-QSDC under the fiber channel. The proposed grading judgment method based on parameter estimation provides a practical and available message processing scheme for CV-QSDC in a practical fiber channel and lays the groundwork for the grading reconciliation.


Competition for water and light in closed-canopy forests: a tractable model of carbon allocation with implications for carbon sinks.
Abstract The dependence of forest productivity and community composition on rainfall is the result of complex interactions at multiple scales, from the physiology of carbon gain and water loss to competition among individuals and species. In an effort to understand the role of these multiscale interactions in the dependence of forest structure on rainfall, we build a tractable model of individual plant competition for water and light. With game-theoretic analyses, we predict the dominant plant allocation strategy, forest productivity, and carbon storage. We find that the amount and timing of rainfall are critical to forest structure. Comparing two forests that differ only in the total time plants spend in water saturation, the model predicts that the wetter forest has fewer fine roots, more leaves, and more woody biomass than the drier forest. In contrast, if two forests differ only in the amount of water available during water limitation, the model predicts that the wetter forest has more fine roots than the drier forest and equivalent leaves and woody biomass. The difference in these responses to increases in water availability has significant implications for potential carbon sinks with rising atmospheric CO2. We predict that enhanced productivity from increased leaf-level water-use efficiency during water limitation will be allocated to fine roots if plants respond competitively, producing only a small and short-lived carbon sink.


Determining the optimum way to maintain quality of life for very elderly patients with advanced bladder cancer and poor performance status: A case report.
Locally advanced bladder cancer causes unpleasant symptoms such as irritative voiding symptoms, lower abdominal pain, gross hematuria and urinary retention, and lowers the quality of life. Treatment decisions in elderly patients may be difficult, as elderly patients are physically and psychologically different from younger patients. An 89-year-old male was referred to hospital for the treatment of an invasive bladder tumor with right hydronephrosis from tumor obstruction. The patient was elderly and did not have a good performance status; therefore curative radical cystectomy or chemotherapy was not indicated. Left retroperitoneoscopic ureterocutaneostomy was performed to alleviate gross hematuria and voiding difficulty. Intensity-modulated radiotherapy was administered 9 days after the surgery to control bleeding in the bladder tumor. After completing 8 days of radiotherapy, the patient was discharged from hospital. The patient exhibited no signs of either postrenal failure or gross hematuria for 7 months prior to mortality. Retroperitoneoscopic ureterocutaneostomy for very elderly patients with advanced bladder cancer with a poor performance status may be an important procedure for alleviating symptoms and improving quality of life.


Sigma-2 ligands and PARP inhibitors synergistically trigger cell death in breast cancer cells.
The sigma-2 receptor is overexpressed in proliferating cells compared to quiescent cells and has been used as a target for imaging solid tumors by positron emission tomography. Recent work has suggested that the sigma-2 receptor may also be an effective therapeutic target for cancer therapy. Poly (ADP-ribose) polymerase (PARP) is a family of enzymes involved in DNA damage response. In this study, we looked for potential synergy of cytotoxicity between PARP inhibitors and sigma-2 receptor ligands in breast cancer cell lines. We showed that the PARP inhibitor, YUN3-6, sensitized mouse breast cancer cell line, EMT6, to sigma-2 receptor ligand (SV119, WC-26, and RHM-138) induced cell death determined by cell viability assay and colony forming assay. The PARP inhibitor, olaparib, sensitized tumor cells to a different sigma-2 receptor ligand SW43-induced apoptosis and cell death in human triple negative cell line, MDA-MB-231. Olaparib inhibited PARP activity and cell proliferation, and arrested cells in G2/M phase of the cell cycle in MDA-MB-231 cells. Subsequently cells became sensitized to SW43 induced cell death. In conclusion, the combination of sigma-2 receptor ligands and PARP inhibitors appears to hold promise for synergistically triggering cell death in certain types of breast cancer cells and merits further investigation.


Stratum corneum modulation by chemical enhancers and lipid nanostructures: implications for transdermal drug delivery.
Skin is the outermost and largest protective covering of the body. The uppermost layer of the skin, stratum corneum also called the horny layer is composed of keratin-filled cells covered by a lipid matrix which shields the skin from physical and chemical entrants. The lipid lamellar structure comprises of ceramides, cholesterol, fatty acids and proteins. Chemical enhancers that mimic the lamellar chemistry, reversibly fluidize the latter can be utilized for enhancing transport of cargo across the epidermis into the dermis. This review deals with the stratum corneum chemistry, mechanisms to modulate its packing with the aid of chemical enhancers, biophysical techniques for characterization and applications in the design of nature-inspired biocompatible lipid nanostructures for transdermal delivery of drugs and bioactive agents.


Hyperparathyroidism secondary to hypovitaminosis D in hypoalbuminemic is less intense than in normoalbuminemic patients: a prevalence study in medical inpatients in southern Brazil.
Hypovitaminosis D has been reported in tropical countries, but this hormone has seldom been studied in Brazil. Our purpose was to study the prevalence of hypovitaminosis D in patients hospitalized in internal medicine wards in Southern Brazil. Possible associated factors were studied. We studied 81 adult patients in early spring. Mean serum 25(OH)D was 12 +/- 8.57 ng/mL; hypovitaminosis D was severe (< 10 ng/mL) in 27 (33.3%) patients, and moderate (> or = 10 ng/mL and < 20 ng/mL) in 36 (44.5%) patients. Clinical evaluation did not yield any data associated with hypovitaminosis D. Serum 25(OH)D levels of up to 20 ng/mL were associated with decreased mean serum total calcium (p = 0.001), ionized calcium (p = 0.01), and phosphorus (p = 0.044) levels, and increased mean serum PTH level (p = 0.001). In a multiple regression model, serum PTH level was independently affected by serum total calcium (p = 0.01), phosphorus (p = 0.009), and albumin (p = 0.009) levels. Hypovitaminosis D patients had lower mean serum albumin levels (p = 0.004), and serum 25(OH)D levels were directly correlated to serum albumin levels (p < 0.0001). Albumin influenced independently PTH response to hypovitaminosis D; normoalbuminemic hypovitaminosis D patients had higher mean serum PTH than hypoalbuminemic patients. Hypovitaminosis D prevalence was very high in medical inpatients in Southern Brazil, in early spring. Nevertheless, secondary hyperparathyroidism was less intense in hypoalbuminemic hypovitaminosis D patients suggesting that in these patients free serum 25(OH)D was closer to normal.


Protective effects of ghrelin against oxidative stress, inducible nitric oxide synthase and inflammation in a mouse model of myocardial ischemia/reperfusion injury via the HMGB1 and TLR4/NF-κB pathway.
The present study aimed to investigate the protective effects of ghrelin against oxidative stress, inducible nitric oxide synthase (iNOS) and inflammation in a mouse model of myocardial ischemia/reperfusion injury (MIRI). In addition, the study aimed to determine its underlying mechanisms. A mouse model of MIRI was used in vivo, in order to ascertain the protective effects of ghrelin on MIRI. Commercial kits were used to measure the serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH) in MIRI mice. Furthermore, Evan's Blue-triphenyltetrazolium chloride solution was used to analyze the protective effects of ghrelin against infarct size in MIRI mice. The underlying mechanisms were determined by measuring MIRI-induced tumor necrosis factor (TNF)‑α, interleukin (IL)‑6, superoxide dismutase (SOD), glutathione (GSH), GSH-peroxidase (GSH‑PX), malondialdehyde (MDA) and caspase‑3/caspase‑9 activities, and iNOS, high mobility group box 1 (HMGB1), Toll‑like receptor 4 (TLR4) and nuclear factor (NF)‑κB protein expression in MIRI mice. The results demonstrated that MIRI led to an increase in infarct size; CK, LDH, TNF‑α, IL‑6, MDA, caspase‑3 and caspase-9 serum levels; and iNOS protein expression. MIRI resulted in inhibition of SOD, FSH and GSH‑PX levels. Conversely, these alterations were significantly inhibited following treatment with ghrelin. In addition, the protective effects of ghrelin against MIRI suppressed HMGB1, TLR4 and NF‑κB protein expression in MIRI mice. The present study revealed that ghrelin exerted protective effects against oxidative stress, iNOS and inflammation in MIRI mice via the HMGB1/TLR4/NF-κB pathway.


Ojibwe lesbian visual AIDS: On the Red Road with Carole laFavor, Her Giveaway (1988), and Native LGBTQ2 film history.
After a century of suppression across the Silent, Classic, and New Hollywood eras, Native Lesbian/Gay media began to proliferate in the post-AIDS 1980s and into the second millennium. Her Giveaway: A Spiritual Journey with AIDS (1988) is a key tribal health AIDS video that exemplified a new contemporary media combination of visual, erotic, and theological sovereignty. The video's central Red Road narrative by the lesbian, Ojibwe, and AIDS/HIV+ spokesperson Carole laFavor emphasizes Native American traditional healing methods involving the medicine wheel and a reclamation of Native lesbian/gay identity.


Phosphoinositide 3-kinases in cell migration.
Cell migration is essential for many biological processes in animals and is a complex highly co-ordinated process that involves cell polarization, actin-driven protrusion and formation and turnover of cell adhesions. The PI3K (phosphoinositide 3-kinase) family of lipid kinases regulate cell migration in many different cell types, both through direct binding of proteins to their lipid products and indirectly through crosstalk with other pathways, such as Rho GTPase signalling. Emerging evidence suggests that the involvement of PI3Ks at different stages of migration varies even within one cell type, and is dependent on the combination of external stimuli, as well as on the signalling status of the cell. In addition, it appears that different PI3K isoforms have distinct roles in cell polarization and migration. This review describes how PI3K signalling is regulated by pro-migratory stimuli, and the diverse ways in which PI3K-mediated signal transduction contributes to different aspects of cell migration.


Reduced interfacial entanglement density affects the boundary conditions of polymer flow.
Hydrodynamic boundary conditions play a crucial role in the flow dynamics of thin films and can be probed by the analysis of liquid front profiles. For long-chained polymer films it was reported that a deviation from a symmetric profile is a result of viscoelastic effects. In this Letter, however, evidence is given that merely a slip-boundary condition at the solid-liquid interface can lead to an asymmetric profile. Variation of molecular weight shows that slippage is directly linked to chain entanglements. We find a reduced entanglement density at the solid-liquid interface (factors 3 to 4), which stresses the importance of considering nonbulk polymer properties in the vicinity of an interface.


Plasma steroid concentrations in conscious and anesthetized rabbits.
The ovarian steroids, estrogen, androgen, and progestin, were measured in the peripheral plasma of adult female rabbits that were either conscious or anesthetized with sodium pentobarbital (nembutal) or halothane. Concentrations of estrogen, androgens, and progestin were determined before and at 10 and 45 min after systemic injection of either buffer or LH. In the controls androgen levels were significantly different between animals anesthetized with nembutal and halothane. However, the greatest treatment effect was noted in plasma progestin concentrations which were significantly elevated in halothane-anesthetized animals in comparison to the conscious and nembutal-anesthetized animals. Following LH, the androgen and progestin levels were significantly elevated over basal levels. Most likely the treatment effect observed in the controls was still present but was overridden by the increased release of steroids following gonadotrophin stimulation. This study suggests that halothane, in contrast to nembutal, does significantly elevate peripheral progestin and androgen levels.


RecA-independent recombination is efficient but limited by exonucleases.
Genetic recombination in bacteria is facilitated by the RecA strand transfer protein and strongly depends on the homology between interacting sequences. RecA-independent recombination is detectable but occurs at extremely low frequencies and is less responsive to the extent of homology. In this article, we show that RecA-independent recombination in Escherichia coli is depressed by the redundant action of single-strand exonucleases. In the absence of multiple single-strand exonucleases, the efficiency of RecA-independent recombination events, involving either gene conversion or crossing-over, is markedly increased to levels rivaling RecA-dependent events. This finding suggests that RecA-independent recombination is not intrinsically inefficient but is limited by single-strand DNA substrate availability. Crossing-over is inhibited by exonucleases ExoI, ExoVII, ExoX, and RecJ, whereas only ExoI and RecJ abort gene-conversion events. In ExoI(-) RecJ(-) strains, gene conversion can be accomplished by transformation of short single-strand DNA oligonucleotides and is more efficient when the oligonucleotide is complementary to the lagging-strand replication template. We propose that E. coli encodes an unknown mechanism for RecA-independent recombination (independent of prophage recombination systems) that is targeted to replication forks. The potential of RecA-independent recombination to mediate exchange at short homologies suggests that it may contribute significantly to genomic change in bacteria, especially in species with reduced cellular exonuclease activity or those that encode DNA protection factors.


Effect of fiber digestibility and conservation method on feed intake and the ruminal ecosystem of growing steers.
Fiber digestibility is an important factor regulating DMI in ruminants. Additionally, the ensiling process can also affect digestibility and chemical composition of the forage. The objective of this study was to investigate effects of sugarcane NDF digestibility (NDFD) and conservation method on intake, rumen kinetics, and the ruminal ecosystem of steers. Eight ruminally cannulated Nellore steers (275±22 kg BW) were used in a replicated 4×4 Latin square design with a 2×2 factorial arrangement of treatments. Two sugarcane genotypes divergent for stalk NDFD were used: IAC86-2480 with high NDFD and SP91-1049 with low NDFD. Experimental diets were formulated with 40% sugarcane, either freshly cut or as silage, and 60% concentrate on a DM basis. Each experimental period lasted for 14 d, with the last 4 d used for determination of intake, ruminal evacuation, and ruminal fluid collection. The effect of fiber digestibility on DM and NDF intake was dependent on the forage conservation method (P=0.01). High NDFD increased (P<0.01) DMI only when sugarcane was offered as silage, having no effect (P=0.41) on DMI when offered as freshly cut. Conservation method had no effect on total ruminal mass, with only a tendency (P<0.10) for greater NDF and indigestible NDF ruminal mass in steers fed the low-NDFD genotype. The NDF turnover and passage rates were greater (P<0.05) for the genotype with high NDFD but only when offered as silage. Liquid turnover rate in the rumen was greater (P=0.02) for diets containing silage, with no effect of genotype (P=0.87). There was no effect of NDFD genotype on ruminal pH (P=0.77); however, diets containing sugarcane as silage increased (P<0.01) ruminal pH. Total concentration of short chain fatty acids (P=0.05) and proportions of propionate (P=0.01) were greater for diets containing fresh sugarcane. Diets with fresh sugarcane increased the ruminal population of Streptococcus bovis (P<0.01) and Ruminococcus albus (P=0.03). The relative population of R. albus was also greater (P=0.04) for diets containing the sugarcane genotype with high NDFD. Feeding diets containing the sugarcane genotype with high NDFD increased Fibrobacter succinogenes population but only when sugarcane was fed as freshly cut (P=0.02). Using sugarcane genotypes with high NDFD can increase intake and benefit fiber-degrading bacteria in the rumen.


Comparing monolithic and microparticular capillary columns for the separation and analysis of peptide mixtures by liquid chromatography-mass spectrometry.
A mixture of ten proteins was trypsinized and injected onto poly-(styrene-divinylben-zene) monolithic columns (60 x 0.20 or 0.10 mm ID) and a column packed with C18 silica particles (75 x 0.075 mm ID), respectively. The columns were eluted at 200-2000 nL/min with gradients of ACN in 0.050% TFA. Eluting peptides were detected by ESI-MS/MS and subsequently identified by database searching. The 100 microm ID monolithic column showed the highest cumulative Mowse scores based on the highest ion scores for the peptides and the largest number of identified peptides. It is shown that the number of identified peptides strongly depends on the dynamic range within the peptide mixture. In consequence, all proteins were identified in a mixture of relatively balanced analyte amounts (12.5-80 fmol) whereas only peptides for six out of ten proteins were found in a sample of high-dynamic range (0.65-270 fmol). The 100 microm monolithic column showed the highest reproducibility for peptide identifications in three consecutive runs. Depending on sample amount, 57-72% of the identified peptides were detectable in each of the three runs of triplicate analyses. The results demonstrate the high suitability of 100 microm monolithic columns for high-resolution peptide separations in proteomic research.


History of medicine and prehistoric orthopedics.
Increasing efforts have been recently made to apply medical technologies to history of medicine of ancient time. Despite the use of molecular biology techniques, the most reliable results have been obtained by the paleopathological study on disease which may be recognized by the observation of stigmata of bones: the datation of skeletal lesions and the findings of cranial and orthopedic lesions indicate that the attempts of cure of bones are typical of early medical activity, dating from the prehistoric antiquity.


High taxonomic resolution surveys and trait-based analyses reveal multiple benthic regimes in North Sulawesi (Indonesia).
As coral reef communities change and reorganise in response to increasing disturbances, there is a growing need for understanding species regimes and their contribution to ecosystem processes. Using a case study on coral reefs at the epicentre of tropical marine biodiversity (North Sulawesi, Indonesia), we explored how application of different biodiversity approaches (i.e., use of major taxonomic categories, high taxonomic resolution categories and trait-based approaches) affects the detection of distinct fish and benthic communities. Our results show that using major categories fails to identify distinct coral reef regimes. We also show that monitoring of only scleractinian coral communities is insufficient to detect different benthic regimes, especially communities dominated by non-coral organisms, and that all types of benthic organisms need to be considered. We have implemented the use of a trait-based approach to study the functional diversity of whole coral reef benthic assemblages, which allowed us to detect five different community regimes, only one of which was dominated by scleractinian corals. Furthermore, by the parallel study of benthic and fish communities we provide new insights into key processes and functions that might dominate or be compromised in the different community regimes.


Multiplex Immunoassay Profiling of Serum in Psychiatric Disorders.
Multiplex immunoassays allow for the rapid profiling of biomarker proteins in biological fluids, using less sample and labour than in single immunoassays. This chapter details the methods to develop and manufacture a 5-plex immunoassay for the Luminex® platform. Although assay development is not included here, the same methods can be used to covalently couple antibodies to the Luminex beads and to label antibodies for the screening of sandwich pairs, if needed. An example will be given for the analysis of five hormones (glucagon-like peptide 1, growth hormone, insulin, leptin and thyroid-stimulating hormone) in serum samples from schizophrenia patients and controls.


Dimensional change card sort performance associated with age-related differences in functional connectivity of lateral prefrontal cortex.
The Dimensional Change Card Sort (DCCS) is a standard procedure for assessing executive functioning early in development. In the task, participants switch from sorting cards one way (e.g., by color) to sorting them a different way (e.g., by shape). Traditional accounts associate age-related changes in DCCS performance with circumscribed changes in lateral prefrontal cortex (lPFC) functioning, but evidence of age-related differences in the modulation of lPFC activity by switching is mixed. The current study therefore tested for possible age-related differences in functional connectivity of lPFC with regions that comprise a larger cognitive control network. Functional magnetic resonance imaging (fMRI) data collected from children and adults performing the DCCS were analyzed by means of independent components analysis (ICA). The analysis revealed several important age-related differences in functional connectivity of lPFC. In particular, lPFC was more strongly connected with the anterior cingulate, inferior parietal cortex, and the ventral tegmental area in adults than in children. Theoretical implications are discussed.


[Liver transplantation: teaching strategies used with patients waiting for surgery].
This study aims to describe the learning results of the implementation of teaching strategies involving patients who will be submitted to liver transplantation. One of these strategies is to give the patients a manual with orientations and the subsequent application of a questionnaire related to the content of the manual. Authors analyzed 13 patients who were waiting for liver transplantation. With respect to the answers regarding the questionnaire, an average of 83.8% of correct responses was given and only one patient got all the questions right. During the correction and the time to clarify their doubts, authors concluded that the opportunity of reading the manual and applying the questionnaire allowed patients and families to get a better understanding about the surgery's most important aspects.


Nonparametric analysis of the impact of inbreeding on production in Jersey cows.
Under dominance, the relationship between a quantitative trait and the inbreeding coefficient (F) is expected to be linear. Epistasis involving dominance effects or selection against inbred individuals can produce nonlinear patterns in the form of inbreeding depression. The form of the relationship between F and yield traits was explored via local regression (LOESS). First-lactation milk, fat, and protein records from 59,778 Jersey cows with at least 6 generations of known pedigree were used. The F ranged from 0.6 to 34% and median F was 6.3%. The LOESS regressions of predicted residuals from an animal model (empirical best linear unbiased predictions, EBLUP) on F were calculated for each trait; the EBLUP model included fixed herd-year-season, age at calving and DIM effects, and random additive genetic effects. The relationship between EBLUP residuals and inbreeding was complex and nonlinear. Yields were unaffected for F <or=7%, and inbreeding depression seemed to stabilize at F >20% for fat and protein yield. For SCS, both parametric and LOESS fits were consistent with the absence of sizable dominance effects. Effects of inbreeding on performance seemed to be more complex than suggested by previous studies based on linear regression. Results should be interpreted with caution because the data were scarce at high levels of F.


Reward and avoidance learning in the context of aversive environments and possible implications for depressive symptoms.
Aversive stimuli in the environment influence human actions. This includes valence-dependent influences on action selection, e.g., increased avoidance but decreased approach behavior. However, it is yet unclear how aversive stimuli interact with complex learning and decision-making in the reward and avoidance domain. Moreover, the underlying computational mechanisms of these decision-making biases are unknown. To elucidate these mechanisms, 54 healthy young male subjects performed a two-step sequential decision-making task, which allows to computationally model different aspects of learning, e.g., model-free, habitual, and model-based, goal-directed learning. We used a within-subject design, crossing task valence (reward vs. punishment learning) with emotional context (aversive vs. neutral background stimuli). We analyzed choice data, applied a computational model, and performed simulations. Whereas model-based learning was not affected, aversive stimuli interacted with model-free learning in a way that depended on task valence. Thus, aversive stimuli increased model-free avoidance learning but decreased model-free reward learning. The computational model confirmed this effect: the parameter lambda that indicates the influence of reward prediction errors on decision values was increased in the punishment condition but decreased in the reward condition when aversive stimuli were present. Further, by using the inferred computational parameters to simulate choice data, our effects were captured. Exploratory analyses revealed that the observed biases were associated with subclinical depressive symptoms. Our data show that aversive environmental stimuli affect complex learning and decision-making, which depends on task valence. Further, we provide a model of the underlying computations of this affective modulation. Finally, our finding of increased decision-making biases in subjects reporting subclinical depressive symptoms matches recent reports of amplified Pavlovian influences on action selection in depression and suggests a potential vulnerability factor for mood disorders. We discuss our findings in the light of the involvement of the neuromodulators serotonin and dopamine.


[MAYbe Less Sugar : a campaign to prevent sugar overconsumption].
Swiss people consume an average of 107g of sugar per day whereas a maximum of 50g is recommended. During May 2023, the MAYbe Less Sugar initiative invited people from the French-speaking part of Switzerland to investigate their use of added sugar. An online calculator enabled them to evaluate it so they could take action. The campaign reached 6 920 participants and more than 11 000 people via the website maybeless-sugar.ch and social networks. In addition, numerous events and media coverage have put sugar at the heart of the debate. Although people who overconsume sugar were targeted, they are still difficult to reach. The 37 partners plead for MAYbe Less Sugar to be continued and involve health professionals as well as politicians in order to change behaviors but also the environment that should become conducive to health for everybody.


Gene therapy with TRAIL against renal cell carcinoma.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in cancer cells. However, TRAIL is not toxic against most normal cells. We have accordingly examined by in vivo electroporation whether TRAIL induces apoptosis in renal cell carcinoma. In addition, combination treatment with TRAIL and 5-fluorouracil (5-FU) against renal cell carcinoma was also investigated. The NC65 renal cell carcinoma line was used as a target. pCAGGS TRAIL was injected into the NC65 tumors in the right flanks of severe combined immunodeficient mice. Tumors were pulsed with the CUY21 electroporator. Electroporation was done once on day 0 or thrice on days 0, 2, and 4. Apoptosis was determined by terminal deoxyribonucleotide transferase-mediated nick-end labeling assay. When TRAIL gene therapy using in vivo i.t. electroporation was done once only, the growth of NC65 tumors was not inhibited. However, when TRAIL gene therapy was done thrice, growth suppression of the NC65 tumors was observed. Transfection of the TRAIL gene by in vivo electroporation induced apoptosis in NC65 tumors. When NC65 cells were treated with TRAIL gene therapy in combination with 5-FU, stronger growth suppression was obtained. TRAIL gene therapy did not induce liver dysfunction in severe combined immunodeficient mice. This study shows that TRAIL gene therapy induced growth suppression and apoptosis in NC65 tumors without severe side effects, and that combination treatment of NC65 cells with TRAIL gene therapy and 5-FU resulted in higher antitumor activity. These findings suggest that TRAIL gene therapy and/or 5-FU may be effective against renal cell carcinoma without harmful toxic effects.


Systematic deletion and mitotic localization of the nuclear pore complex proteins of Aspergillus nidulans.
To define the extent of the modification of the nuclear pore complex (NPC) during Aspergillus nidulans closed mitosis, a systematic analysis of nuclear transport genes has been completed. Thirty genes have been deleted defining 12 nonessential and 18 essential genes. Several of the nonessential deletions caused conditional phenotypes and self-sterility, whereas deletion of some essential genes caused defects in nuclear structure. Live cell imaging of endogenously tagged NPC proteins (Nups) revealed that during mitosis 14 predicted peripheral Nups, including all FG repeat Nups, disperse throughout the cell. A core mitotic NPC structure consisting of membrane Nups, all components of the An-Nup84 subcomplex, An-Nup170, and surprisingly, An-Gle1 remained throughout mitosis. We propose this minimal mitotic NPC core provides a conduit across the nuclear envelope and acts as a scaffold to which dispersed Nups return during mitotic exit. Further, unlike other dispersed Nups, An-Nup2 locates exclusively to mitotic chromatin, suggesting it may have a novel mitotic role in addition to its nuclear transport functions. Importantly, its deletion causes lethality and defects in DNA segregation. This work defines the dramatic changes in NPC composition during A. nidulans mitosis and provides insight into how NPC disassembly may be integrated with mitosis.


[10-year retrospective analysis of the sequelae of loco-regional treatment of breast cancer].
With a minimum follow-up period of 10 years, the incidence of sequelae after loco-regional treatment of 349 breast cancers remains low, being dominated by lymphoedema. Rare after treatment by irradiation alone, lymphoedema appears more frequently in patients treated by radio-surgical association, in spite of a moderate dose of radiation. If a rigorous technique is carried out, the possibility of achieving satisfactory local control in the axilla with radiation alone without neurological sequelae, therefore brings into question the need for axillary dissection without clinically significant adenopathy.


Gait analysis in swine, sheep, and goats after neurologic injury: a literature review.
Medical research on neurologic ailments requires representative animal models to validate treatments before they are translated to human clinical trials. Rodents are the predominant animal model used in neurological research despite limited anatomic and physiologic similarities to humans. As a result, functional testing designed to assess locomotor recovery after neurologic impairment is well established in rodent models. Comparatively, larger, more clinically relevant models have not been as well studied. To achieve similar locomotor testing standardization in larger animals, the models must be accessible to a wide array of researchers. Non-human primates are the most relevant animal model for translational research, however ethical and financial barriers limit their accessibility. This review focuses on swine, sheep, and goats as large animal alternatives for transitional studies between rodents and non-human primates. The objective of this review is to compare motor testing and data collection methods used in swine, sheep, and goats to encourage testing standardization in these larger animal models. The PubMed database was analyzed by searching combinations of swine, sheep, and goats, neurologic injuries, and functional assessments. Findings were categorized by animal model, data collection method, and assessment design. Swine and sheep were used in the majority of the studies, while only two studies were found using goats. The functional assessments included open pen analysis, treadmill walking, and guided free walking. Data collection methods included subjective behavioral rating scales and objective tools such as pressure-sensitive mats and image-based analysis software. Overall, swine and sheep were well-suited for a variety of assessment designs, with treadmill walking and guided free walking offering the most consistency across multiple trials. Data collection methods varied, but image-based gait analysis software provided the most robust analysis. Future studies should be conducted to standardize functional testing methods after neurologic impairment in large animals.


Immune complexes suppress IFN-γ-induced responses in monocytes by activating discrete members of the SRC kinase family.
The regulation of the innate and the adaptive immune responses are extensively intertwined and tightly regulated. Ag-driven immune responses that are modulated by immune complexes (ICs) are known to inhibit IFN-γ-dependent MHC class II expression. We have previously demonstrated that ICs dramatically inhibit IFN-γ-induced activation of human monocytes through the activation of the FcγRI signaling pathway. In the present study we further explore the mechanisms by which ICs regulate IFN-γ activation of human monocytes. We demonstrate that members of the SRC kinase family (SKF) are key mediators of IFN-γ pathway suppression: inhibitors of the SKF reverse the ability of ICs to suppress IFN-γ signaling. Small interfering RNA was used to target specific members of the SKF. The data indicate that SRC and LYN are both required for ICs to elicit their immunosuppressive activity, whereas FYN does not appear to contribute to this function. Similarly, the kinase SYK, though not a member of the SKF, is also demonstrated to be involved in this IC-mediated immunosuppression. Our data suggest a mechanism whereby ICs directly inhibit inflammatory signals by crosslinking FcγRI, resulting in the activation of the specific phosphotyrosine kinases SRC, LYN, and SYK and the concomitant suppression of the IFN-γ signaling pathway.


Differences in Spatiotemporal Parameters Between Trained Runners and Untrained Participants.
Gómez-Molina, J, Ogueta-Alday, A, Stickley, C, Tobalina, JC, Cabrejas-Ugartondo, J, and García-López, J. Differences in spatiotemporal parameters between trained runners and untrained participants. J Strength Cond Res 31(8): 2169-2175, 2017-The aim of this study was to compare the spatiotemporal parameters of trained runners and untrained participants with the same foot strike pattern (rearfoot) during running at controlled speeds. Twenty-one participants were classified in 2 groups according to their training experience: Trained (n = 10, amateur runners with long distance training experience) and Untrained (n = 11, healthy untrained participants). Anthropometric variables were recorded, and the participants performed both a submaximal (between 9 and 15 km·h) and a graded exercise running test (from 6 km·h until exhaustion) on a treadmill. Physiological (V[Combining Dot Above]O2max, heart rate, running economy [RE], peak speed …) and biomechanical variables (contact and flight times, step rate, and length) were simultaneously registered. Trained runners showed higher step rate and shorter step length than the Untrained group at the same running speeds (between 4 and 7%, p ≤ 0.05) and at the same physiological intensities (between 7 and 11%, p ≤ 0.05). However, there were no differences in contact and flight times between groups. Significant differences (p ≤ 0.05) and large effect sizes (Cohen's d) between groups were found for body mass, sum of 6 skinfolds, V[Combining Dot Above]O2max, peak speed, and ventilatory threshold and respiratory compensation threshold speeds. The Trained group also showed a ∼7% better RE (ml·kg·km) than the Untrained group. In conclusion, adopting higher step rate and shorter step length may be an adaptive mechanism of the Trained group to reduce injury risk and possibly improve RE. However, contact and flight times were consistent regardless of training level.


Clinically relevant concentrations of beta2-adrenergic agonists stimulate maximal cyclic adenosine monophosphate-dependent airspace fluid clearance and decrease pulmonary edema in experimental acid-induced lung injury.
To determine whether clinically relevant airspace concentrations of beta2-adrenergic agonists stimulated maximal alveolar fluid clearance rates and to determine whether beta2 agonist therapy decreased pulmonary edema in experimental acute lung injury. Prospective randomized laboratory investigation. University-affiliated laboratory. Sprague Dawley rats. Dibutyryl cyclic adenosine monophosphate (cAMP), salmeterol, albuterol, and isoproterenol in normal rat lung. Salmeterol in a rat model of acid-induced lung injury. Basal alveolar fluid clearance was 7.6 +/- 2.2 %/hr. Maximal cAMP-dependent alveolar fluid clearance rate was 32.9 +/- 10.9 %/hr (p <.05). Racemic albuterol 10(-5) M, salmeterol 10(-6) M, and isoproterenol 10(-6) M each stimulated alveolar fluid clearance to a level comparable to maximal cAMP-dependent alveolar fluid clearance. Compared with basal rates, alveolar fluid clearance was increased by both racemic albuterol 10(-6) M (14.5 +/- 3.0%, p <.05) and R-enantiomer 10(-6) M (15.0 +/- 4.6%, p <.05), but there was no difference between the two groups. Intra-alveolar salmeterol 10 (-6) M attenuated the degree of pulmonary edema following acid-induced lung injury. Extravascular lung water increased to only 180 +/- 30 microL with salmeterol treatment, compared with 296 +/- 65 microL in saline-treated rats 4 hrs after acid injury (p <.05). This decrease in lung water was accompanied by a 2.4-fold increase in the rate of alveolar fluid clearance at 4 hrs in the salmeterol-treated group. Lung endothelial permeability, expressed as extravascular plasma equivalents, was reduced to 64 +/- 9 microL with salmeterol compared with 119 +/- 51 microL in saline-treated rats 4 hrs after acid injury (p <.05). Clinically relevant airspace concentrations of beta2-adrenergic agonists a) stimulate maximal cAMP-dependent airspace fluid clearance in normal lungs and b) reduce pulmonary edema in acid aspiration-induced lung injury by increasing alveolar fluid clearance and decreasing endothelial permeability. Clinical studies are required to determine whether beta2-adrenergic agonists improve outcome in patients with acute lung injury.


Cardioprotective effect of ischemic preconditioning is preserved in food-restricted senescent rats.
Ischemic preconditioning (PC) has been proposed as an endogenous form of protection against-ischemia reperfusion injury. We have shown that PC does not prevent postischemic dysfunction in the aging heart. This phenomenon could be due to the reduction of cardiac norepinephrine release, and it has also been previously demonstrated that age-related decrease of norepinephrine release from cardiac adrenergic nerves may be restored by caloric restriction. We investigated the effects on mechanical parameters of PC against 20 min of global ischemia followed by 40 min of reperfusion in isolated hearts from adult (6 mo) and "ad libitum"-fed and food-restricted senescent (24 mo) rats. Norepinephrine release in coronary effluent was determined by high-performance liquid chromatography. Final recovery of percent developed pressure was significantly improved after PC in adult hearts versus unconditioned controls (85.2 +/- 19% vs. 51.5 +/- 10%, P < 0.01). The effect of PC on developed pressure recovery was absent in ad libitum-fed rats, but it was restored in food-restricted senescent hearts (66.6 +/- 13% vs. 38.3 +/- 11%, P < 0.05). Accordingly, norepinephrine release significantly increased after PC in both adult and in food-restricted senescent hearts, and depletion of myocardial norepinephrine stores by reserpine abolished the PC effect in both adult and in food-restricted senescent hearts. We conclude that PC reduces postischemic dysfunction in the hearts from adult and food-restricted but not in ad libitum-fed senescent rats. Despite the possibility of multiple age-related mechanisms, the protection afforded by PC was correlated with increased norepinephrine release, and it was blocked by reserpine in both adult and food-restricted senescent hearts. Thus caloric restriction may restore PC in the aging heart probably via increased norepinephrine release.


Brain and Organ Uptake in the Rhesus Monkey in Vivo of Recombinant Iduronidase Compared to an Insulin Receptor Antibody-Iduronidase Fusion Protein.
Mucopolysaccharidosis type I (MPSI) is caused by mutations in the gene encoding the lysosomal enzyme, α-l-iduronidase (IDUA), and patients with MPSI are currently treated with IDUA enzyme replacement therapy (ERT). However, the majority of MPSI patients have severe CNS involvement, and conventional ERT does not treat the brain. The failure of ERT to treat the brain is believed to be due to the lack of IDUA transport through the blood-brain barrier (BBB). However, BBB transport of IDUA has not been directly measured, to date. BBB transport of IDUA may be enhanced by fusion of the enzyme to a monoclonal antibody (mAb) against the human insulin receptor (HIR). The HIRMAb binds the insulin receptor on the BBB to trigger transport into the brain and acts as a molecular Trojan horse to deliver IDUA to brain cells. Therefore, the purpose of the present investigation was to compare, side-by-side, the BBB transport of IDUA alone and the HIRMAb-IDUA fusion protein in the Rhesus monkey in vivo. Each protein was radio-iodinated by conjugation with the [125I]-Bolton-Hunter reagent and injected intravenously (IV) in the primate. The uptake by brain, and peripheral organs, was measured by whole body autoradiography. The results show there is no transport of IDUA alone into the brain, but that the brain uptake of the HIRMAb-IDUA fusion protein is high, 1.2% injected dose/brain. There is comparable uptake of the IDUA and the HIRMAb-IDUA fusion protein by peripheral organs, where uptake is primarily controlled by the mannose 6-phosphate receptor. The work suggests that treatment of MPSI with the HIRMAb-IDUA fusion protein will be as effective as IDUA in peripheral organs, but offer the benefit of treatment of the central nervous system in MPSI.


Medical mistrust in the context of Ebola: Implications for intended care-seeking and quarantine policy support in the United States.
This investigation explores Ebola conspiracy beliefs, a form of medical mistrust, and their potential impact on health behavior. Results of an online survey in the United States in December 2014 demonstrated that 16 percent of 202 participants held conspiracy beliefs. Participants who were less knowledgeable about Ebola, more mistrustful of medical organizations, and more xenophobic more strongly endorsed conspiracy beliefs. Participants who more strongly endorsed conspiracy beliefs reported that they would be less likely to seek care for Ebola and were less supportive of quarantining people returning from West Africa. Results suggest that medical mistrust may influence health behaviors during infectious disease outbreaks.


Differential immunolocalization of sulfonylurea receptors in mouse and rat ureters.
The receptors for sulphonylurea (SURs) are known to be expressed in the mouse kidney, but their expression in the ureter is undefined. Owing to the physiological and pharmacological significance of SURs, the localization of SUR in ureters of adult mice and rats was investigated through immunohistochemistry. Animals were perfused transcardially with 4% paraformaldehyde and tissues were processed for immunohistochemistry using polyclonal antisera against SUR2A and SUR2B (SUR1) receptor proteins. Sections were incubated with primary and secondary antisera and developed with aminoethylcarbazole as a chromogen. A differentiated localized staining pattern of SUR proteins in rat and mouse ureters is demonstrated. In the mouse, immunoreactivity of SUR2A was predominantly confined to the cytoplasmic portion of epithelial cells and blood vessels, with comparatively low-level staining found in smooth muscle. In contrast, SUR2B (SUR1) immunoreactivity was absent in mouse ureters. In rats, SUR2A immunoreactivity was localized only in the blood vessels, while SUR2B (SUR1) immunoreactivity was localized in the epithelial cell cytoplasm. Tissue specificity of SUR is demonstrated in the two species of rodents and suggests a role of SUR proteins in urinary metabolism pertaining possibly to salt handling and maintenance of the smooth muscle tone.


[Evaluation of a screening test for urinary infection].
The interest of using a reagent strip (Multistix-8 SG, Ames, Miles Laboratories) as a screen for urinary tract infection was evaluated in a clinical study involving several sites and 2,183 adult urine specimens of which 340 were infected. The results are expressed in terms of sensitivity, specificity, predictive value of a negative and positive test. The predictive value of a negative test for nitrites in combination with leucocytes (97.5%) justifies the use of the reagent strip in eliminating non-infected urine.


Exacerbation of Spinal Stenosis Symptoms Following Neuraxial Anesthesia in an Achondroplastic Cesarean Section.
We report the case of an achondroplastic female who presented with acute neurologic decline following epidural anesthesia for an elective cesarean section. Achondroplasia presents unique anatomical challenges to anesthesiologists in perioperative management, and cesarean sections are standard for achondroplastic pregnancies. High rates of spinal stenosis and lumbar radiculopathy in this patient population make administration of epidural analgesia technically challenging and may increase the risk of neurologic injury. Ultrasound is an effective means of administering epidural anesthesia for most patients; however, its utility is user-dependent and more challenging for those with obesity and abnormal spinal anatomy, both of which are common in achondroplasia. Cephalic and thoracic anatomical features in achondroplasia can also make general anesthesia challenging. Therefore, preoperative imaging may help guide preoperative planning based on patient anatomy and individual risk factors to reduce the risks of complications in this patient population. This report includes details from the patient's prenatal care, cesarean section, and 18 months of follow-up.


Dissecting microsatellite instability in colorectal cancer: one size does not fit all.
Microsatellite instability (MSI) marks distinct subsets of tumors in many cancer types and is caused by mutations in genes required for mismatch repair. A recent report analyses the molecular foundations of MSI-positive colorectal cancers and reveals substantial molecular heterogeneity, which might have consequences for the potential use of immunotherapy in MSI-positive cancers.See related research by Sveen et al. 10.1186/s13073-017-0434-0.


A randomized trial comparing the efficacy and tolerability of two HAART strategies at two years in antiretroviral naive patients.
The use of HAART combining 2 nucleoside analogues reverse transcriptase inhibitors (NRTIs) plus one protease inhibitor (PI) or 2 NRTIs + 1 non-nucleoside reverse transcriptase inhibitor (NNRTI) has shown comparable efficacy. The study was designed to compare long term (2 years) effectiveness of two antiretroviral (ARV) treatment strategies in patients not previously treated: starting with a nelfinavir based HAART switching to nevirapine in case of failure or side effects or the reverse sequence. This multicenter, randomized, open label clinical trial enrolled ARV-naïve HIV patients with CD4 counts below 500 cells/mm3. They were randomly assigned to start ddI + d4T + nelfinavir (switching to ZDV + 3TC + NEV in case of failure or toxicity) (PI-NEV arm) or ddI + d4T + nevirapine, switching to ZDV + 3TC + NFV in case of failure or toxicity (NEV-PI arm). The primary study endpoint was the Kaplan-Meier estimates of the time to failure after switching to second regimen if necessary (considering failure as two consecutive plasma HIV-1 RNA determinations above 200 copies/mL, death, a new category C event or toxicity leading to treatment discontinuation of the second regimen) after a minimum follow-up of two years. A total of 137 patients were evaluable (67 and 70 in the PI-NEV and NEV-PI arms respectively). Baseline characteristics did not differ among groups. Kaplan-Meier estimates of time to failure did not show differences between the two arms neither in the on-treatment (OT) analysis (log rank test, p = 0.81) nor in the intent-to-treat (ITT) analysis (p = 0.58). At 24 months, the estimated proportion of patients free of failure were 72% and 66% respectively in the PI-NEV and NEV-PI arms OT analysis (p = 0.54) and 73% and 64% in the PI-NEV and NEV-PI arms in the ITT analysis (p = 0.49). The difference in the median in CD4+ lymphocyte count at 24 months was not significantly different in the two groups: 393 and 307 CD4 cells/mm3 in the PI-NEV and NEV-PI arms respectively (p = 0.167). The incidence of adverse events (AEs) in the two arms was very similar: 50 (75%) in the PI-NEV and 54 (70%) in the NEV-PI group, as it was for grade 3-4 AEs leading to drug switching. At two years both treatments strategies (PI-NEV vs NEV-PI) had a high and comparable efficacy and were generally well tolerated.


Incidence and risk factors for depression and anxiety disorders: results from a 34-year longitudinal Swedish cohort study.
This study is based on a total cohort (N = 192) of people born in 1902 and 1903 and living in southern Sweden. Subjects were assessed at baseline when 67 years of age and on eight further occasions over 34 years or until death. The participation rate in the nine examinations ranged from 78-100%. Interviews, psychological tests, and medical examinations were used as well as information on medical diagnoses from primary health care records and hospital records. The cumulative probability for the development of clinical depression during the follow-up was 8% and for anxiety 6%. The incidence rate for depression and for anxiety was highest during the period 67-81 years. Persons with poor financial status were more likely to be diagnosed with depression but no significant risk factor for anxiety was found. Only 14% developed depression and anxiety during the follow-up period, females more often than men. The strongest risk factors for the development of depression were perceived economic problems.


Effect of Ti and Au buffer layers on controlling the density and wettability of well-aligned ZnO nanorod arrays grown on different substrates.
ZnO nanorod arrays (NRAs) have potential applications as building blocks for nanoscale electronic, optoelectronic, and sensing applications. The density of ZnO NRAs is controlled by a simple low-cost hydrothermal growth process. It is shown that Ti and Au thin buffer layers can be used to control ZnO NRA density up to an order of magnitude on a wide variety of substrates including bare glass AZO, ZnO seeded AZO, FTO and ITO substrates, respectively. We investigate surface morphological, structural and optical properties of ZnO NRAs by field emission scanning electron microscopy, transmission electron microscopy, X-ray diffraction, Raman, and photoluminescence spectroscopy measurements, respectively. To highlight the importance of NRA density, wettability measurements show large dependence on density and static water contact angles range from as low as ∼23° to as large as ∼142°. These results indicate that the capability to control the density of ZnO NRAs, and thus their wettability, can have additional implications such as in their use in biosensors, field emission, dye-sensitized solar-cells (DSSCs), and photocatalytic activity in addition to potential light trapping effects over wide spectral ranges.


The migration and attrition of Strongyloides ratti in naive and sensitized rats.
Compressed organ autoradiography has been utilized to study the migration of the homogonic strain of Strongyloides ratti from the site of skin penetration to the gut. This transit is characterized by rapid disappearance of parasites from the cutaneous site of infection, followed by vascular dispersal throughout all organs investigated. For the first time, parasite migration in both naive and previously sensitized hosts is compared; the principal stations of migration are the same in the two groups although there is a quantitative difference in accumulation of parasites with time in these stations. Parasite attrition occurs in both groups of animals; however, in naive rats it is not manifest until day 20-25 post challenge, whereas in sensitized rats immune elimination occurs as early as 48 h post challenge.


CPT1B, a metabolic molecule, is also an independent risk factor in CN-AML.
Fatty acid oxidation has been considered as an important energy source for tumorigenesis and development. Several studies have investigated the role of CPT1A, a kind of fatty acid oxidation rate-limiting enzyme, in AML. However, prognostic value and regulatory network of another subtype, CPT1B in AML remains elusive. This study aims to clarify the independent prognostic role of CPT1B in CN-AML based on clinical data and molecular level data (mRNA, miRNA and lncRNA). The aim of this study is to investigate the prognostic value of CPT1B in AML patients. First, we analyzed the CPT1B expression in AML cohort via the online database "GEPIA". Subsequently, miRNA-mRNA and ceRNA networks were constructed to help predict the role of CPT1B in AML. Several molecules which showed the prognostic value and metabolic function of CPT1B were identified. Finally, the expression of CPT1B in our own cohort of 324 CN-AML patients was analyzed to clarify the results. It was found that CPT1B was markedly higher in AML patients compared to normal people and this upregulation was associated with the poor clinical outcome. Several molecules revealed the possible regulatory mechanism of CPT1B in AML. CPT1B is a potential prognostic factor and a therapeutic target for AML treatment.


Role of chymase-dependent angiotensin II formation in regulating blood pressure in spontaneously hypertensive rats.
Vascular smooth muscle cells in spontaneously hypertensive rats (SHR) express angiotensin II-forming chymase (rat vascular chymase [RVCH]), which may contribute to blood pressure regulation. In this study, we studied whether chymase-dependent angiotensin II formation contributes to the regulation of blood pressure in SHR. The systolic blood pressure in 16-week-old Wistar-Kyoto (WKY) rats was 113 +/- 9 mmHg, compared to 172 +/- 3 mmHg in SHR. Using synthetic substrates for measuring angiotensin-converting enzyme (ACE) and chymase activities, it was found that both ACE and chymase activities in extracts from SHR aortas were significantly higher than in those from WKY rat aortas. Using angiotensin I as a substrate, angiotensin II formation in SHR was found to be significantly higher than that in WKY rats, and its formation was completely suppressed by an ACE inhibitor, but not by a chymase inhibitor. RVCH mRNA expression could not be detected in aorta extracts from either WKY rats or SHR. In carotid arteries isolated from WKY rats and SHR, angiotensin I-induced vasoconstriction was completely suppressed by an ACE inhibitor, but not by a chymase inhibitor. Angiotensin I-induced pressor responses in both WKY rats and SHR were also completely inhibited by an ACE inhibitor, but they were not affected by a chymase inhibitor. In SHR, an ACE inhibitor and an angiotensin II receptor blocker showed equipotent hypotensive effects, but a chymase inhibitor did not have a hypotensive effect. These results indicated that chymase-dependent angiotensin II did not regulate blood pressure in SHR in the present study.


Reward prediction-errors weighted by cue salience produces addictive behaviours in simulations, with asymmetrical learning and steeper delay discounting.
Dysfunction in learning and motivational systems are thought to contribute to addictive behaviours. Previous models have suggested that dopaminergic roles in learning and motivation could produce addictive behaviours through pharmacological manipulations that provide excess dopaminergic signalling towards these learning and motivational systems. Redish (2004) suggested a role based on dopaminergic signals of value prediction error, while (Zhang et al., 2009) suggested a role based on dopaminergic signals of motivation. However, both models present significant limitations. They do not explain the reduced sensitivity to drug-related costs/negative consequences, the increased impulsivity generally found in people with a substance use disorder, craving behaviours, and non-pharmacological dependence, all of which are key hallmarks of addictive behaviours. Here, we propose a novel mathematical definition of salience, that combines aspects of dopamine's role in both learning and motivation within the reinforcement learning framework. Using a single parameter regime, we simulated addictive behaviours that the (Zhang et al., 2009; Redish, 2004) models also produce but we went further in simulating the downweighting of drug-related negative prediction-errors, steeper delay discounting of drug rewards, craving behaviours and aspects of behavioural/non-pharmacological addictions. The current salience model builds on our recently proposed conceptual theory that salience modulates internal representation updating and may contribute to addictive behaviours by producing misaligned internal representations (Kalhan et al., 2021). Critically, our current mathematical model of salience argues that the seemingly disparate learning and motivational aspects of dopaminergic functioning may interact through a salience mechanism that modulates internal representation updating.