Hierarchical processing in the prefrontal cortex in a variety of cognitive domains.
This review scrutinizes several findings on human hierarchical processing within the prefrontal cortex (PFC) in diverse cognitive domains. Converging evidence from previous studies has shown that the PFC, specifically, BA44, may function as the essential region for hierarchical processing across the domains. In language fMRI studies, BA 44 was significantly activated for the hierarchical processing of center-embedded sentences and this pattern of activations was also observed in artificial grammar. The same pattern was observed in the visuo-spatial domain where BA44 was actively involved in the processing of hierarchy for the visual symbol. Musical syntax, which is the rule-based arrangement of musical sets, has also been construed as hierarchical processing as in the language domain such that the activation in BA44 was observed in a chord sequence paradigm. P600 ERP was also engendered during the processing of musical hierarchy. Along with a longstanding idea that a human's number faculty is developed as a "by-product of language faculty", BA44 was closely involved in hierarchical processing in mental arithmetic. This review extended its discussion of hierarchical "processing" to hierarchical "behavior", that is, human action which has been referred to as being hierarchically composed. Several lesion and TMS studies supported the involvement of BA44 for hierarchical processing in the action domain. Lastly, the hierarchical organization of cognitive controls was discussed within the PFC, forming a cascade of top-down hierarchical processes operating along a posterior-to-anterior axis of the lateral PFC including BA44 within the network. It is proposed that PFC is actively involved in different forms of hierarchical processing and specifically BA44 may play an integral role in the process. Taking levels of proficiency and subcortical areas into consideration may provide further insight into the functional role of BA44 for hierarchical processing.


Does a fall prevention educational programme improve knowledge and change exercise prescribing behaviour in health and exercise professionals? A study protocol for a randomised controlled trial.
Falling in older age is a serious and costly problem. At least one in three older people fall annually. Although exercise is recognised as an effective fall prevention intervention, low numbers of older people engage in suitable programmes. Health and exercise professionals play a crucial role in addressing fall risk in older adults. This trial aims to evaluate the effect of participation in a fall prevention educational programme, compared with a wait-list control group, on health and exercise professionals' knowledge about fall prevention and the effect on fall prevention exercise prescription behaviour and confidence to prescribe the exercises to older people. A randomised controlled trial involving 220 consenting health and exercise professionals will be conducted. Participants will be individually randomised to an intervention group (n=110) to receive an educational workshop plus access to internet-based support resources, or a wait-list control group (n=110). The two primary outcomes, measured 3 months after randomisation, are: (1) knowledge about fall prevention and (2) self-perceived change in fall prevention exercise prescription behaviour. Secondary outcomes include: (1) participants' confidence to prescribe fall prevention exercises; (2) the proportion of people aged 60+ years seen by trial participants in the past month who were prescribed fall prevention exercise; and (3) the proportion of fall prevention exercises prescribed by participants to older people in the past month that comply with evidence-based guidelines. Outcomes will be measured with a self-report questionnaire designed specifically for the trial. The trial protocol was approved by the Human Research Ethics Committee, The University of Sydney, Australia. Trial results will be disseminated via peer reviewed journals, presentations at international conferences and participants' newsletters. Trial protocol was registered with the Australian and New Zealand Clinical Trials Registry (Number ACTRN12614000224628) on 3 March 2014.


Long-term consequences of pelvic trauma patients with thromboembolic disease treated with inferior vena caval filters.
The use of inferior vena cava (IVC) filters for prevention of pulmonary embolism (PE) in high-risk trauma patients is well accepted. High rates of recurrent venous thrombosis, however, and postthrombotic syndrome (PTS) have been reported in nonsurgical patients with medical comorbidities. Patients with pelvic trauma and thromboembolic disease have a unique thrombogenic pathophysiology, and the long-term consequences of filter placement in these patients are unknown. We sought to evaluate the outcomes of patients who sustained pelvic trauma, and who developed venous thrombosis and were treated with a vena caval filter. A cohort of 102 consecutive patients was treated for a pelvic or acetabular fracture who developed deep vein thrombosis (DVT) preoperatively and had a caval filter placed. Thromboembolic events and complications were evaluated by both retrospective chart review and a prospective questionnaire. Eighty-eight patients (86%) returned the questionnaire at an average follow-up of 4 years. No patients were readmitted to the hospital for recurrent venous thrombosis or PE. Six patients (7%) described new swelling in the lower extremities, and one (1%) demonstrated evidence of PTS. No deaths occurred related to PE. The use of IVC filters appears to be safe and effective in preventing PE in patients with pelvic trauma and established venous thrombosis. The risk of recurrent DVT is low and PTS is negligible in these patients. Filter placement use is not associated with the same long-term complications as in patients with thrombosis because of chronic medical comorbidities.


Surgical treatment of acute complicated diverticulitis in the elderly.
Although the true prevalence is unknown, colonic diverticulosis is one of the most common disease of the digestive tract in Western countries. Based on administrative data of hospitalized patients, the incidence of diverticulitis has been increasing in last decades. In general, elderly patients undergo less frequently an elective colonic resection; but a substantial part of emergency surgeries is performed in elderly patients. In these older patients the choice of any clinical and surgical option is to be correlated not only to the severity of diverticulitis, but also to general status and the co-existing comorbidities. In this regard, it is mandatory that all patients undergo a multidimensional, comprehensive geriatric assessment to correctly identify those who are fit, vulnerable or frail. The analysis of data currently available highlights three relevant elements: type and severity of peritoneal contamination, hemodynamic conditions (stable or unstable), and concomitant comorbidities (fit or frail status). There is no single ideal surgical treatment that can be considered as gold standard for all clinical presentations; the final clinical decision-making should always be based on patient's general health status, severity of peritonitis and of sepsis. In a septic elderly patient who is hemodynamically unstable, treatment should be as prompt as possible independent of the Hinchey's stage, and could include either a Mickulicz stoma or a DCS strategy. In an elderly patient who is fit and hemodynamically stable, the surgical options are similar to those in a younger patient. If a patient is frail but hemodynamically stable, he should be treated with a Hartmann's procedures.


The Mitotic Exit Network integrates temporal and spatial signals by distributing regulation across multiple components.
GTPase signal transduction pathways control cellular decision making by integrating multiple cellular events into a single signal. The Mitotic Exit Network (MEN), a Ras-like GTPase signaling pathway, integrates spatial and temporal cues to ensure that cytokinesis only occurs after the genome has partitioned between mother and daughter cells during anaphase. Here we show that signal integration does not occur at a single step of the pathway. Rather, sequential components of the pathway are controlled in series by different signals. The spatial signal, nuclear position, regulates the MEN GTPase Tem1. The temporal signal, commencement of anaphase, is mediated by mitotic cyclin-dependent kinase (CDK) phosphorylation of the GTPase's downstream kinases. We propose that integrating multiple signals through sequential steps in the GTPase pathway represents a generalizable principle in GTPase signaling and explains why intracellular signal transmission is a multi-step process. Serial signal integration rather than signal amplification makes multi-step signal transduction necessary.


Lifelong reductions of PKMζ in ventral hippocampus of nonhuman primates exposed to early-life adversity due to unpredictable maternal care.
Protein kinase Mζ (PKMζ) maintains long-term potentiation (LTP) and long-term memory through persistent increases in kinase expression. Early-life adversity is a precursor to adult mood and anxiety disorders, in part, through persistent disruption of emotional memory throughout life. Here we subjected 10- to 16-wk-old male bonnet macaques to adversity by a maternal variable-foraging demand paradigm. We then examined PKMζ expression in their ventral hippocampi as 7- to 12-yr-old adults. Quantitative immunohistochemistry reveals decreased PKMζ in dentate gyrus, CA1, and subiculum of subjects who had experienced early-life adversity due to the unpredictability of maternal care. Adult animals with persistent decrements of PKMζ in ventral hippocampus express timid rather than confrontational responses to a human intruder. Persistent down-regulation of PKMζ in the ventral hippocampus might reduce the capacity for emotional memory maintenance and contribute to the long-lasting emotional effects of early-life adversity.


Polylactic Acid/Lignin Composites: A Review.
With the gradual depletion of petroleum resources and the increasing global awareness of environmental protection, biodegradable plastics are receiving more and more attention as a green substitute for traditional petroleum-based plastics. Poly (lactic acid) is considered to be the most promising biodegradable material because of its excellent biodegradability, biocompatibility, and good processability. However, the brittleness and high cost limit its application in more fields. Lignin, as the second largest renewable biopolymer in nature after cellulose, is not only rich in reserves and low in cost, but it also has an excellent UV barrier, antioxidant activity, and rigidity. The molecular structure of lignin contains a large number of functional groups, which are easy to endow with new functions by chemical modification. Currently, lignin is mostly treated as waste in industry, and the value-added utilization is insufficient. The combination of lignin and poly (lactic acid) can on the one hand solve the problems of the high cost of PLA and less efficient utilization of lignin; on the other hand, the utilization of lignocellulosic biomass in compounding with biodegradable synthetic polymers is expected to afford high-performance wholly green polymer composites. This mini-review summarizes the latest research achievements of poly (lactic acid)/lignin composites. Emphasis was put on the influence of lignin on the mechanical properties of its composite with poly (lactic acid), as well as the compatibility of the two components. Future research on these green composites is also prospected.


[Effects of propofol or sevoflurane on cerebral regional oxygen saturation (rSO2) during one-lung ventilation].
The present study was designed to evaluate the alteration of cerebral regional oxygen saturation (rSO2) associated with propofol or sevoflurane during one-lung ventilation (OLV). Fifty patients scheduled for a lung lobectomy were randomly assigned to propofol or sevoflurane group. General anesthesia was maintained with propofol (target controlled infusion; 2-3 mcg x ml(-1)) in propofol group (n=25), and sevoflurane (end-tidal concentration 1-2%) in sevoflurane group (n=25), being adjusted to maintain BIS values between 40 and 60. BIS and rSO2 values were continuously monitored. Arterial blood gas analysis was performed as follows: during two-lung ventilation before OLV (baseline), during the first 120 minutes of OLV and at the end of OLV and surgery. During OLV rSO2 was significantly lower than baseline in both groups. The values of rSO2 were not significantly different between the groups at each time. We could not find accurate correlation between rSO2 and other factors monitored. We conclude OLV leads to the decrease of rSO2, but there is no difference in the alteration of rSO2 between propofol and sevoflurane group. To maintain adequate rSO2, we should consider together in combination with respiratory, circulatory or metabolic index and depth of anesthesia.


Low dose MK-801 protects against iron-induced oxidative changes in a rat model of focal epilepsy.
We have used chemiluminescence measurements to examine the relationship between free radical formation and excitotoxicity in a post-traumatic epilepsy model. For this purpose, seven days after injecting iron in rat brain cortices, we measured luminol- and lucigenin-enhanced chemiluminescence in different brain regions (ipsilateral cortex, contralateral cortex, hypothalamus and hippocampus). In all brain regions (except contralateral cortices) both luminol- and lucigenin-enhanced chemiluminescence were increased in iron-injected group compared to saline-injected control group. These increases returned to control values in iron-injected rats pretreated with MK-801. Our results suggest that both free radicals and excitatory amino acids play important roles in the development of post-traumatic epilepsy and that MK-801 has protective effects against iron-induced chemiluminescence formation.


Effects of the 3- and 4-methoxy and acetamide substituents and solvent environment on the electronic properties of N-substituted 1,8-naphthalimide derivatives.
The photophysical properties of polar molecules in solution with an intramolecular charge-transfer effect in the excited state depend strongly on the polarity and proticity of the solvents. UV-visible spectra of 1,8-naphthalimide and some N-substituted derivatives in acetic acid, acetonitrile, dichloromethane, and p-dioxane were carried out. Several molecular cluster geometries formed with N-substituted 1,8-naphthalimide derivatives and a large set of random positioning of some solvent molecules in their environment were optimized by a semiempirical method. It provided a complete screening of possible solute-solvent configurations and resulted in a multiple minima hypersurface of the supramolecular systems. With such local minima energies, the main thermodynamic association functions were found. They also provided selected cluster geometries for calculations of vertical electronic transitions with a time-dependent density functional theory (TD-DFT), if the lowest energy structures were considered. Calculated vertical electronic transition energies at the TD-DFT level were compared with experimental data. The experimental absorption UV-visible spectra for the six compounds in the four solvents were performed in our laboratory. Moreover, X-ray photoelectron spectroscospy of the 1,8-naphthalimide was carried out in the ICP-CSIC laboratory. Thermodynamic function values show different association energies between each solvent and the molecules, in correlation with the possibility of hydrogen bond formation and the polarity and dielectric constant of the solvents. The 3- and 4-acetamide 1,8-naphthalimide derivatives have the highest conformer number and the most negative Gibbs free association energy values for a determined solvent. This indicates the importance of the entropic factors.


Interlaboratory comparison of autoradiographic DNA profiling measurements. 4. Protocol effects.
The observed total interlaboratory uncertainty in restriction fragment length polymorphism (RFLP) measurements is sufficiently small to be of little significance given current forensic needs. However, as the number of RFLP data increase, further reduction in the total uncertainty could help minimize the resources required to evaluate potential profile matches. The large number of data available enable quantitative estimation of the within-laboratory imprecision and among-laboratory bias contributions to the total uncertainty. Some small but consistent among-laboratory measurement biases can be attributed to specific procedural or materials differences. The bias direction is often fragment-specific and thus unpredictable for unknown samples. Actions that would minimize currently recognized sources of interlaboratory bias include the following: (1) all laboratories should use the same algorithm for data interpolation, (2) all laboratories should use the same sizing ladders, (3) each laboratory should prepare control DNA and sample DNA in the same manner and with the identical reagents, (4) all laboratories should adopt a uniform policy on ethidium bromide use, and (5) all laboratories should adopt the same control DNA sizing acceptability criteria.


Transplacental cocaine exposure: a mouse model demonstrating neuroanatomic and behavioral abnormalities.
Between 10% and 15% of infants born in urban America today have been exposed to cocaine in utero. Clinical studies have suggested that impairment of brain growth is the single best marker of significant prenatal cocaine exposure, and postnatal developmental compromise seen in a subset of affected children as a consequence of that exposure. We have developed an animal model, in mice, of prenatal cocaine exposure that has allowed us to dissociate the direct effects of cocaine in altering fetal development from the indirect effects associated with cocaine-induced malnutrition. We find that transplacental cocaine exposure independently impairs fetal brain and body growth and results in behavioral deficits and permanent alterations in neocortical cytoarchitecture in exposed offspring.


Scoping Review: Ethical Considerations in Online Ethnographic Research With Military Populations.
Researchers using online ethnographic methods to study military communities must employ higher standards of ethical practice. Military populations may face significant risk if reidentified in research. These requirements are especially salient for online data collection. This review questions how and to what extent military online ethnographers are addressing ethics considerations. We charted evidence from seven military studies using an online ethnographic method. Findings reveal that most online military ethnographers did not utilize sufficient ethical safeguards in their studies. Additionally, they did not document or transparently disclose the ethical steps they may have taken. This study argues implementing ethical safeguards is especially important for protecting vulnerable military populations. We present a strategy for evaluating ethics practices in online ethnographic research and provide best practices for military online ethnographers.


Development and Validation of the Awareness of Narrative Identity Questionnaire (ANIQ).
The utility of a narrative approach to identity and its role in psychological functioning are becoming increasingly recognized across various fields of inquiry. The current study aimed to develop a quantitative, self-report measure of the awareness of narrative identity and how globally coherent one's autobiographical memories are perceived to be, specifically, in terms of temporal ordering, causal associations, and the perception of unifying themes. The construct validity and reliability of the Awareness of Narrative Identity Questionnaire (ANIQ) were assessed across three studies. In the first study, exploratory factor analysis of the responses of a large sample ( N = 441, M [age in years] = 33.1, SD = 15.2) to an initial item pool resulted in a 20-item four-factor structure congruent with the proposed subscales, and convergent and divergent validity were established. In the second study, and with a different sample ( N = 320, M [age in years] = 26.2, SD = 4.0), further evidence for the factor structure was provided through confirmatory factor analysis. Validity findings from Study 1 were replicated and extended on, and test-retest reliabilities were found to be high ( r = .72-.79). Importantly, in the third study ( N = 71, M [age in years] = 24.9, SD = 6.9), criterion validity was established, whereby the ANIQ subscales were demonstrated to be associated with dimensions of narrative coherence coded from written turning-point narratives. Across all studies, the internal reliabilities for the subscales were high (α = .86-.96). The ANIQ represents a valid, psychometrically sound, and novel method of assessing the awareness of narrative identity and autobiographical memory coherence.


Rifampin, a useful drug for nonmycobacterial infections.
Rifampin has clinical efficacy against a wide variety of organisms, including Staphylococcus aureus, Legionella pneumophila, group A Streptococcus, Brucella sp, Haemophilus influenzae, and Neisseria meningitidis, as well as in vitro activity against penicillin-resistant Streptococcus pneumoniae, Neisseria gonorrhoeae, Chlamydia trachomatis, Haemophilus ducreyi, and many gram-negative rods. Rifampin is a useful drug for several types of bacterial infections because of its broad spectrum of activity, excellent tissue penetration, and low side effect profile. In combination with other antibiotics, it may be effective when conventional therapies are not.


Bibliometrics Analysis and Visualization of Sarcopenia Associated with Osteoporosis from 2000 to 2022.
Recent years have seen an increased awareness of sarcopenia in the cross field of osteoporosis and sarcopenia. The goal of this study was to evaluate current bibliometric characteristics and the status of cross-sectional studies between osteoporosis and sarcopenia. Publications related to osteoporosis and sarcopenia published between January 2000 and November 2022 were extracted from the Web of Science Core Collection; bibliometric and visualization were performed by Microsoft Office Excel, VOSviewer, Citespace, and R. A total of 1128 documents written by 5791 authors from 1758 organizations in 62 countries and published in 405 journals were identified. USA was the leading country with the highest publication and total citation. University of Melbourne contributed the most publications, while Tufts University had the largest citations. Osteoporosis International was the most influential journals in this field with the highest publications, citations and H index. Cooper C was the most influential author, who published the 20 studies, had the highest local citations and the highest H index. The keywords were classified into 6 clusters: Cluster 1 (aging), Cluster 2 (frailty) and Cluster 3 (osteosarcopenia). Our bibliometric results revealed that the global osteoporosis and sarcopenia-related research increased rapidly from 2000 to 2022, suggesting it was a promising area of research for the future. The future trends in the cross field of sarcopenia and osteoporosis would be the molecular mechanisms of crosstalk between muscles and bones, safety and efficacy interventions with a dual effect on muscle and bone and osteosarcopenia.


Aneurysm Outreach Inc., a nonprofit organization, offers community-based, ultrasonography screening for abdominal aortic aneurysms.
Aneurysm Outreach Inc. (AOI; http://www.alink.org) is a nonprofit volunteer organization founded in 1999 whose aim is to (a) raise public awareness about aneurysms; (b) stimulate and fund genetic research through donations; and (c) coordinate a support network for aneurysm patients and their families. Since abdominal ultrasonography examination of an asymptomatic individual is not presently reimbursed by health insurance in the United States, one of the initiatives supported by AOI is to have free ultrasonography screening for abdominal aortic aneurysm (AAA) for those most at risk. One of the initiatives supported by AOI is to have free ultrasonography screening for abdominal aortic aneurysm (AAA). To meet this goal, a free screening program was initiated in September 2001 and by November 2004 approximately 3,000 participants were screened and 61 (2.0%) participants were confirmed to have a dilated aorta and were referred to their primary care physicians or vascular surgeons for further follow-up and treatment, if indicated.


Childhood Poverty and Cognitive Development in Latin America in the 21st Century.
For at least eight decades, researchers have analyzed the association between childhood poverty and cognitive development in different societies worldwide, but few of such studies have been carried out in Latin America. The aim of the present paper is to systematically review the empirical studies that have analyzed the associations between poverty and cognitive development in children under 18 years of age from Latin American and Caribbean countries between 2000 and 2015. This analysis takes into consideration the country where the work was conducted, the experimental and analytical design, sample size and composition, cognitive and poverty paradigms implemented, levels of analysis, and the inclusion of mediation analyses. Through these, we identify common patterns in the negative impact of poverty that have been repeatedly verified in the literature in other continents; we also call attention to a set of issues regarding sample, design, paradigms, impact, and mediation analyses that should be considered in future studies in the region.


Effect of an automated notification system for deteriorating ward patients on clinical outcomes.
Delayed response to clinical deterioration of ward patients is common. We performed a prospective before-and-after study in all patients admitted to two clinical ward areas in a district general hospital in the UK. We examined the effect on clinical outcomes of deploying an electronic automated advisory vital signs monitoring and notification system, which relayed abnormal vital signs to a rapid response team (RRT). We studied 2139 patients before (control) and 2263 after the intervention. During the intervention the number of RRT notifications increased from 405 to 524 (p = 0.001) with more notifications triggering fluid therapy, bronchodilators and antibiotics. Moreover, despite an increase in the number of patients with "do not attempt resuscitation" orders (from 99 to 135; p = 0.047), mortality decreased from 173 to 147 (p = 0.042) patients and cardiac arrests decreased from 14 to 2 events (p = 0.002). Finally, the severity of illness in patients admitted to the ICU was reduced (mean Acute Physiology and Chronic Health Evaluation II score: 26 (SD 9) vs. 18 (SD 8)), as was their mortality (from 45% to 24%; p = 0.04). Deployment of an electronic automated advisory vital signs monitoring and notification system to signal clinical deterioration in ward patients was associated with significant improvements in key patient-centered clinical outcomes. ClinicalTrials.gov, NCT01692847 . Registered on 21 September 2012.


An extractive membrane biofilm reactor as alternative technology for the treatment of methyl tert-butyl ether contaminated water.
Among the strategies developed for contaminated groundwater bioremediation, those based on the use of bacteria adhering to inert supports and establishing biofilms have gained great importance in this field. Extractive membrane biofilm reactor (EMBFR) technology offers productive solutions for the removal of volatile and semi-volatile compounds. EMBFR technology is based on the use of extractive semipermeable membranes through which contaminants migrate to the biological compartment in which microorganisms with pollutant biotransformation and/or mineralization capacities can grow, forming an active biofilm on the membrane surface. The objective of this study was to assess the use of three bacterial strains (Paenibacillus sp. SH7 CECT 8558, Agrobacterium sp. MS2 CECT 8557, and Rhodococcus ruber EE6 CECT 8612), as inoculum in a lab-scale EMBFR running for 28 days under aerobic conditions to eliminate methyl tert-butyl ether (MTBE) from water samples. Three different hydraulic retention times (1, 6, and 12 h) were employed. MTBE degradation values were determined daily by a gas GC-MS technique, as well as suspended bacterial growth. The biofilm established by the bacterial strains on the semipermeable membrane was detected by Field-Emission Scanning Electron Microscopy (FESEM) at the end of each experiment. The acute toxicity of the treated effluents and biomedium was determined by Microtox© assay (EC50 ).The results achieved from the MTBE degradation, biofilm formation, and toxicity analysis indicated that bacterial strains MS2 and EE6 were the best options as selective inoculum, although further research is needed, particularly with regard to their possible use as a mixed culture. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1238-1245, 2016.


[Weaknesses in healthcare for persons with gluten-related disorders].
Gluten-related disorders affect 1% to 6% of the population, with complications and high risk of short and long-term morbidity and mortality. Since 2009, Brazil has a Clinical Protocol of Therapeutic Guidelines for Celiac Disease, but there are frequent complaints by persons with gluten-related disorders concerning the lack of healthcare professionals' knowledge of this topic and the difficulties related to healthcare, for both diagnosis and treatment. This study aimed to understand the weaknesses in healthcare perceived by persons with gluten-related disorders. An online qualitative survey was conducted in the Living Without Gluten group on Facebook, consulting the records saved by the group for 65 months, which totaled 510 posts and the respective comments. The data were grouped in categories, and thematic content analysis was performed, adopting the theoretical references on healthcare. The analysis revealed that the searches for diagnosis and adequate treatment were often described as a forced pilgrimage, resulting from shortcomings in healthcare, including lack of up-to-date knowledge on gluten-related disorders among the healthcare professionals and problems in the physician-patient relationship. Weaknesses in patient care and late diagnoses contribute to increasing the risk of complications and deaths. In this context, the Living Without Gluten group plays a leading role as a support group and network of solidarity, favoring increased awareness and empowerment of numerous Brazilians with gluten-related disorders.


Xerostomia - A Comprehensive Review with a Focus on Mid-Life Health.
Xerostomia is defined as the subjective complaint of a dry mouth. Xerostomia is common in menopausal women owing to the hormonal changes which take place during midlife. Studies show a higher incidence of oral cancer in the postmenopausal period which substantiates the theory of estrogen deficiency in carcinogenesis. Radiotherapy in the treatment of these cancers can lead to oral dryness. Other etiological factors of xerostomia include systemic diseases commonly occurring in middle-aged individuals and xerogenic drugs. Saliva plays a pivotal role in the maintenance of oropharyngeal health and xerostomia can severely impair the quality of life. The aim of this review was to provide vital information pertaining to the etiology, signs, diagnosis, and treatment of xerostomia with an emphasis on midlife health. The articles for this review were obtained from PubMed Central, Google Scholar, EBSCO, Science Direct, Medknow, Scopus, EMBASE, Web of Science, and authorized textbooks published between 1988 and 2021.


Age-dependent differences in the efficacy of cancer immunotherapy in C57BL and AKR mouse strains.
While tumor incidence increases with age, tumor growth and metastasis often proceed at a slower rate in aged organisms. The mechanisms underlying this age-related reduced tumor development may suggest therapeutic modalities appropriate for the aged. Decreased tumor aggressiveness in the old was shown to be related to altered immune response. Consequently, the aim of the present study was to assess whether cancer immunotherapy has an age-dependent effect. Only a few studies have compared cancer immunotherapy efficiency as a function of age, most showing lower inhibition in older animals. In the present study, we tested the effect of two immunomodulators, levamisole and BCG, on two tumors, B16 melanoma and AKR lymphoma, in mice of different ages. We demonstrated a higher efficiency of immunotherapy in aged as compared to young mice, particularly at low immunomodulator doses. While decreased T cell function during aging is apparently established, nonspecific immunity is more preserved or even enhanced in later life. We found an increased number of macrophages in tumors of old compared to young mice and an increase in MAC-1+ cells in old levamisole-treated compared to non-treated mice. The stronger therapeutic effect of this immunomodulator in old mice might thus be due to an increased macrophage-mediated anti-tumoral effect.


Frovatriptan: a review of drug-drug interactions.
To investigate the potential for interactions involving drugs likely to be coadministered with frovatriptan. Frovatriptan is a new 5-hydroxytryptamine (5-HT)(1B/1D) agonist. Preclinical data suggest that the pharmacokinetic and pharmacological profile of frovatriptan may differ from that of the currently available triptans. The potential for interactions between frovatriptan and other drugs was investigated using in vitro methods, studies in healthy volunteers, and retrospective analysis of data from phase I trials. In vitro, frovatriptan was principally metabolized by cytochrome P-450 (CYP) 1A2 but was found not to be an inhibitor or inducer of this or other CYP isoenzymes. Frovatriptan was only a weak inhibitor of monoamine oxidase at very high concentrations in vitro and was not a substrate for this enzyme (unlike some other triptans). Coadministration with moclobemide, at doses known to inhibit monoamine oxidase-A, did not affect the pharmacokinetics of frovatriptan. Binding to plasma proteins was low (15%), and binding to erythrocytes was moderate (60%) and unlikely to be a source of interaction with other drugs. The pharmacokinetics of frovatriptan were not affected by moderate alcohol intake. There were slight increases in area under the curve and maximum concentration on concomitant administration with the combined oral contraceptives, propranolol, and fluvoxamine; and slight decreases in these parameters on concomitant administration with ergotamine and in tobacco smokers; these findings were considered to have no clinical significance in view of frovatriptan's large therapeutic index (well tolerated at doses ranging from 2.5 to 40 mg). These effects can be attributed primarily to modification of CYP1A2 activity but their impact is limited, probably due to frovatriptan also undergoing renal clearance and the likely role of blood cell binding in controlling the amount of unbound drug available for elimination. Because it has no inhibitory or inducing effect on CYP isoenzymes and is only slightly bound to plasma proteins, it is unlikely that frovatriptan will alter the pharmacokinetics of concomitantly administered drugs. Frovatriptan, therefore, appears to have a low risk of interaction with other drugs, and adjustments of dose are unlikely to be required when it is coadministered with other agents.


Thin-film magnetization dynamics on the surface of a topological insulator.
We theoretically study the magnetization dynamics of a thin ferromagnetic film exchange coupled with a surface of a strong three-dimensional topological insulator. We focus on the role of electronic zero modes imprinted by domain walls (DWs) or other topological textures in the magnetic film. Thermodynamically reciprocal hydrodynamic equations of motion are derived for the DW responding to electronic spin torques, on the one hand, and fictitious electromotive forces in the electronic chiral mode fomented by the DW, on the other. An experimental realization illustrating this physics is proposed based on a ferromagnetic strip, which cuts the topological insulator surface into two gapless regions. In the presence of a ferromagnetic DW, a chiral mode transverse to the magnetic strip acts as a dissipative interconnect, which is itself a dynamic object that controls (and, inversely, responds to) the magnetization dynamics.


[Cerebrospinal Fluid and Blood Biomarkers in Alzheimer's Disease].
To cope with an aging society, development of disease-modifying drugs for Alzheimer's disease (AD) is essential. Currently, only symptomatic treatments that suppress clinical manifestations are available. Amyloid-β42 (Aβ42) is an AD-related pathogenic molecule that triggers development of AD pathology; thus, decreasing Aβ42 in the brain is a promising candidate for AD therapy. Numerous pharmaceutical companies have developed therapeutic drugs against Aβ42, such as β-secretase inhibitors, γ-secretase inhibitors, and anti-Aβ monoclonal antibodies, but in clinical trials for patients with mild to moderate AD, these drugs did not meet the expected endpoints. These results suggest that earlier administration of these drugs to individuals who have not yet developed cognitive decline, but have AD pathological changes in the brain or high risk of developing these changes, may be beneficial. To enable such early treatment, preclinical AD biomarkers are required. In this review, we comment on current AD biomarkers in cerebrospinal fluid and in blood. We also explain CSF/blood APL1β, which is a candidate surrogate marker for Aβ42 in the brain.


Arterial fibromuscular dysplasia. Report of a case with involvement of the aorta and review of the literature.
A case of fibromuscular dysplasia (FMD) with involvement of the aorta is described in a 44-year-old woman. So far only 3 cases of aortal FMD have been mentioned, all in female patients. Our observation is characterized by a solitary stenosis of the lower abdominal aorta and it resembles histologically the "intimal fibroplasia" type of renal FMD. The review of the literature about FMD in general reveals that mostly the renal arteries are affected, followed by cervical artery FMD with only rare occurrence in other vessels. Though the etiology is basically unknown several factors have been made responsible, namely hereditary disposition, congenital rubella infection, female hormones, paucity of the vasa vasorum, and stretch-traction-stress. The disease has been classified into several histological subgroups and also according to the roentgenologic form which typically shows a "string of beads" appearance. There is a definitive female sex preponderance of 5:1, which is the same for all affected vessels; whereas in respect to age there is a marked distinction in so far that renal FMD patients on average are 11 years younger than patients with the cervicocephalic form of the disease.


Awareness and use of family planning methods among iTaukei women in Fiji and New Zealand.
iTaukei women's awareness and practice of family planning methods was investigated in New Zealand and Fiji to ascertain differences in behaviour within the context of changing developmental settings. The study was cross-sectional in nature and recruited women aged 18 years and over from three suburbs in Suva, Fiji, and five cities in New Zealand. Overall, 352 women participated in the study, 212 in Fiji and 140 in New Zealand. The study found that living in New Zealand was significantly associated with lower odds of being aware of family planning (OR 0.4, 95%CI 0.2-0.9, p=0.029) and using family planning methods (OR 0.5, 95%CI 0.2-0.9, p=0.027). Tertiary education was found to increase the odds of being aware (OR 2.8, 95%CI 1.3-6.2, p=0.009) and of using (OR 3.9, 95%CI 1.9-7.8, p=0.000) family planning. Despite the greater availability of services and higher standards of living experienced in New Zealand compared with Fiji, there was no improvement in awareness and use of family planning among New Zealand participants. Implications for public health: Reduced awareness and use of family planning in New Zealand indicates a need for better targeting of services among minority Pacific ethnic groups.


Seven fractions to deliver partial breast irradiation: the toxicity is Low.
To assess toxicity and clinical outcome, in breast cancer patients treated with external beam partial breast irradiation (PBI) consisting of 35 Gy in 7 daily fractions (5 Gy/fraction). Patients affected by early-stage breast cancer were enrolled in this phase II trial. Patients had to be 60 years old or over and treated with breast conservative surgery for early stage invasive carcinoma. Seventy-three patients were analyzed. Median follow-up was 40 months. The proposed schedule was well tolerated. No Grade 3 toxicity was documented. Late toxicity was assessable for all the treated patients. Two patients (2.7%) developed Grade 2 pain 6 months after PBI. Four patients (5%) developed asymptomatic fat necrosis. Grade 2 fibrosis was observed in 5 patients (6.7%). No correlation was found between early and late toxicity and the type of adjuvant systemic therapy (no therapy vs. hormonal therapy vs. chemotherapy). No statistical correlation between dosimetric parameters and toxicity was found. Patients who developed Grade 2 radiation fibrosis had not higher radiation volumes to the untreated normal breast than those without fibrosis. Cosmesis was judged good/excellent in the majority of the cases (93%). One patient relapsed locally, and one developed distant metastases, corresponding to a 5-year local control and distant metastases-free survival of 98% and 96.7%, respectively. 35 Gy in 7 daily fractions is an effective and well-tolerated regimen to deliver PBI.


[Daily intake of macro and trace elements in the diet. 4. Sodium, potassium, calcium, and magnesium].
To complete the picture of the daily dietary intake of minerals, sodium, potassium, calcium and magnesium have now been considered. The study has been carried out in the Italian Marches Region after carefully evaluating the food consumption habits of the population. The foodstuffs comprising the 70 diets examined were collected in institutional canteens and private homes immediately prior to meals. The food was sampled ready for consumption as it had thus undergone the various preparation and cooking procedures, during which considerable changes in mineral content occur. In comparison with the various food consumption standards, the amount of sodium found appears excessively high (4.8 g/d) whereas that of magnesium is insufficient (0.24 g/d). A high sodium intake, and more recently a high Na/K ratio, have been associated with hypertension. Also a lack of magnesium and a high Ca/Mg ratio have repeatedly been associated with hypertension risk. The data to emerge from our study: a high sodium intake, an insufficiency of magnesium, and thus high Na/K and Ca/Mg ratios, would appear likely to enhance cardiovascular disease risk. Even though not all Authors agree on the existence of such correlations, a more correct diet as regards mineral intake is undoubtedly something to encourage.


Successful physostigmine treatment of acute dothiepin intoxication.
We report on a severe intoxication with the tricyclic antidepressant dothiepin. A treatment with a continuous infusion of physostigmine was successful and improved the ventricular arrhythmia. Dothiepin and its active metabolites were determined in plasma and urine by HPLC.


[Socio-demographic and psychopathological analysis of child and adolescent attempted suicides].
to analyze socio-demographic and psychopathological factors affecting attempted suicides by youths admitted to the Hospital de Niños de Córdoba (Argentina). prospective study based on clinical interviews and tests conducted on 80% of the patients admitted to the hospital in 2006. The significance level established for statistical comparisons was 0.05. 70% of the patient were female and 30% were male, the latter having a lower mean age than the female group (p0.001). The most common type of autoagression was the ingestion of medicines (87%). The most significant precedents in the psychopatological histories were: previous attempted suicides and conduct disorders (p0.002); 79% of them were not under treatment. Diagnoses at the moment of admission were: Mood Disorder (74%) and Disocial Disorder (74%). the main characteristics of this group are previous attempted suicides and psychopathological conditions which could have been diagnosed and treated previously.


COVID Alert: Factors Influencing the Adoption of Exposure Notification Apps Among Canadian Residents.
The continued emergence of new variants of COVID-19 such as the Delta and Omicron variants, which can cause breakthrough infections, indicates that contact tracing and exposure notification apps (ENAs) will continue to be useful for the long haul. However, there is limited work to uncover the strongest factors that influence their adoption. Using Canada's "COVID Alert" as a case study, we conducted an empirical, technology-acceptance study to investigate the key factors that account for users' intention to use ENAs and the moderating effect of important human and design factors. Our path model analysis shows that four factors significantly influence the adoption of COVID Alert among Canadian residents: perceived risk, perceived usefulness, perceived trust, and perceived compatibility. The overall model explains over 60% of intention to use, with type of design, use case (functional interface), and adoption status moderating the strength of the relationships between the four factors and intention to use. We discuss these findings and make recommendations for the design of future ENAs.


[The routine coagulation tests along with activated protein C resistance (APC-R) in population of women applying for oral contraceptives].
The routine coagulation tests along with activated protein C resistance (APC-R) were studied in North-Eastern Poland women, applying for oral contraceptives. The APTT, PT and fibrinogen concentration were evaluated in 128 women, aged 20-40 years, by means of nephelometric method. For estimation of APC-R, Coatest APC Resistance V test was used. The abnormalities in routine coagulation test were found in 13.3% of studied women. The resistance to activated protein C was observed among 4.3% of women with normal results of routine coagulation tests. The thrombotic event occurred in one of five APC-R positive woman. There was no correlation between APC-V ratio and APTT, PT or fibrinogen values.


Complementary expression and heterophilic interactions between IgLON family members neurotrimin and LAMP.
Neurotrimin (Ntm) and the limbic system-associated membrane protein (LAMP) are members of the IgLON (LAMP, OBCAM, Ntm) family of glycorylphosphatidylinositol anchored neural cell adhesion molecules. We previously reported that LAMP and Ntm promote adhesion and neurite outgrowth via a homophilic mechanism, suggesting that these proteins promote the formation of specific neuronal circuits by homophilic interactions. In this report, we have further characterized the expression and binding specificity of Ntm. Using a newly generated monoclonal antibody to Ntm, we demonstrated that this protein is largely expressed in a complementary pattern to that of LAMP in the nervous system, with co-expression at a few sites. Ntm is expressed at high levels in sensory-motor cortex and, of particular note, is transiently expressed in neurons of cortical barrel fields and corresponding thalamic "barreloids." Binding of a recombinant, soluble form of Ntm to CHO cells expressing either Ntm or LAMP demonstrates that Ntm and LAMP interact both homophilically and heterophilically. In contrast to conventional growth-promoting activity of Ig superfamily members, LAMP strongly inhibits the outgrowth of Ntm-expressing dorsal root ganglion (DRG) neurons in a heterophilic manner. These anatomical and functional data support the concept that homophilic and heterophilic interactions between IgLON family members are likely to play a role in the specification of neuronal projections via growth promoting and inhibiting effects, respectively.


[Ultrasound study possibilities in evaluation of anatomical structures in children with congenital cleft of upper lip and palate].
Congenital cleft of upper lip and palate (CCULP) is one of the most widely spread and complicated developmental malformation of maxillofacial region, its frequency makes up for 16.4% of the total number of inherited defects. Ultrasound study (USS) let receive clinically significant information about anatomical structures peculiarities of upper lip, alveolar process and palate in patients with crest CCULP that could be important for surgical and prosthetic treatment planning and also significant for assessment of immediate and postponed treatment results. Verification of the received during surgical interventions and orthodontic manipulations data showed high diagnostic reliability of the USS results.


Environmental factors of celiac disease: cytotoxicity of hulled wheat species Triticum monococcum, T. turgidum ssp. dicoccum and T. aestivum ssp. spelta.
In the present paper, the toxicity of prolamines derived from three cereals with a different genome was investigated in human colon cancer Caco-2/TC7 and human myelogenous leukemia K562(S) cells. The purpose of this study was to investigate if species from ancient wheat could be considered as healthy food crops devoid or poor in cytotoxic prolamines for celiac disease. Cytotoxicity was measured in terms of inhibition of cell growth, activation of apoptosis, release of nitric oxide (NO), detection of tissue transglutaminase (TG II) and alteration of transepithelial electrical resistance (TEER) on Caco-2/Tc7 and K562 (S) cell agglutination. Peptic-tryptic (PT) digest from bread wheat (T. aestivum S. Pastore) was used as a positive control. PT digests of prolamins from spelt wheat (T. aestivum ssp. spelta) were found to exert toxic effects on Caco-2/TC7 cells and to agglutinate K562(S) cells. Increased amounts of NO and TG II expression were observed in Caco-2/TC7 cells exposed to 1 mg/mL of spelt prolamins, suggesting that spelt wheat can induce cellular mechanisms implicated in the pathogenesis of celiac disease. By contrast, the PT digests from monoccum wheat (Triticum monococcum) and farro wheat (T. turgidum ssp. dicoccum) did not exhibit any negative effects on Caco-2/TC7 and K562(S) cells. The results have shown a constant and significant toxic effect of spelt wheat which is not shared by the two other ancient cereals. Future studies on celiac intestinal organ cultures are needed to increase the prospects of breeding programs aimed at developing wheat cultivars potentially tolerated by most celiac patients.


Projected Numbers of Ischemic Strokes Recorded in the Austrian Stroke-Unit Registry from 2012 to 2075.
This study analyzed the number of patients with ischemic strokes recorded in the Austrian Stroke-Unit Registry with the aim of projecting this number from 2012 to 2075 and to highlight that the Austrian health system will face a dramatic increase in older patients within the next few decades. Current demographic information was obtained from EUROSTAT, and information on age- and sex-stratified 1-year incidence rates of ischemic stroke were obtained from the Austrian Stroke-Unit Registry. Sensitivity analysis was performed by analyzing the projections based on predicted ageing, main, and growth population scenarios, and with stratification by age and gender. The total number of ischemic strokes recorded in the Austrian Stroke-Unit Registry was 8,690 in 2012 and is expected to increase to 15,826, 15,626, or 18,134 in 2075 according to the ageing, main, and growth scenarios, respectively. The corresponding numbers of patients are projected to increase or decrease within different age strata as follows (100%=number of registered ischemic strokes in 2012): 0-40 years, 100%/99% (males/females); 40-50 years, 83%/83%; 50-60 years, 98%/97%; 60-70 years, 126%/119%; 70-80 years, 159%/139%; 80-90 years, 307%/199%; and 90+ years, 894%/413%. The ageing population in Austria will result in the number of patients increasing considerably from 2012 to 2075, to 182%, 180%, or 208% (relative to 100% in 2012) according to the ageing, main, and growth scenarios, respectively; the corresponding value among those aged 80+ years is 315%, 290%, or 347%. These figures demonstrated the importance of improving primary preventive measures. The results of this study should provide a basis for discussions among health-care professionals and economists to face the future large financial burden of ischemic stroke on the Austrian health system.


Phasic variations of extracellular potassium during fictive swimming in the lamprey spinal cord in vitro.
The lamprey spinal cord in vitro can generate the motor pattern underlying locomotion, which can be recorded with suction electrodes in the ventral roots. To test if the extracellular level of potassium changed during rhythmic activity, potassium-sensitive microelectrodes were used to systematically (every 25 micrometers) explore the level of extracellular potassium [K+]e in different loci in the transverse plane of the spinal cord. During fictive locomotion the baseline level of [K+] increased with 0.08-0.4 mM in the grey matter. As a rule phasic variations of up to 0.2 mM, correlated to each ventral root burst, were superimposed on the tonic deviation of [K+]e. Changes in this range may cause a moderate depolarization of the spinal neurones and might also affect other neuronal functions including the rhythm-generating circuits.


DNA Three-Way Junction for Differentiation of Single-Nucleotide Polymorphisms with Fluorescent Copper Nanoparticles.
A label- and enzyme-free fluorescent sensor for the detection of single-nucleotide polymorphisms (SNPs) at room temperature is proposed, using new copper nanoparticles (CuNPs) as fluorescent reporters. The CuNPs were constructed by using a DNA three-way junction (3WJ) template. In this assay, two complementary adenine/thymine-rich probes can hybridize with the wild-type target simultaneously to construct a 3WJ structure, serving as an efficient scaffold for the generation of CuNPs. However, the CuNPs produce weak fluorescence when the probes bind with a mutant-type target. SNPs can be identified by the difference in fluorescence intensity of the CuNPs. This SNPs detection strategy is straightforward, cost-effective, and avoids the complicated procedures of labeling or enzymatic reactions. The fluorescent sensor is versatile and can be applied to all types of mutation because the probes are programmable. Moreover, the sensor exhibits good detection performance in biological samples.


The sequence of cell and matrix changes in atherosclerotic lesions of coronary arteries in the first forty years of life.
We have studied the cell and matrix composition of normal intima and of atherosclerotic lesions in the coronary arteries of 691 subjects less than 40 years old. These arteries were obtained at autopsy and fixed by perfusion with glutaraldehyde under physiological pressure. A defined segment of the left coronary artery, known for its susceptibility to develop advanced lesions, was studied by light and electron microscopy. The initial intimal lesion occurred in infants and consisted in an increase in intimal macrophages and presence of isolated lipid-laden macrophages (foam cells). At puberty, more substantial accumulations of foam cells, accompanied now by lipid droplets in smooth muscle cells and by thinly scattered extracellular lipid (fatty streaks), were present. After puberty, an increasing number of subjects had intermediate lesions and atheroma. Intermediate lesions, characterized by greatly increased extracellular lipid, were the link between fatty streaks and atheroma. Atheroma was characterized by a massive core of extracellular lipid that damaged arterial structure by displacing normal intimal cells and matrix. In the third and more often in the fourth decade, some atheroma contained greatly increased collagen and smooth muscle cells above the lipid core (fibroatheroma). Collagenization and thickening were more marked when evidence of thrombotic deposits was present on the surface or within lesions. Smooth muscle cells were present in the intima of all subjects from birth. In early lesions, lipid in the intima was not associated with an increase in the number of smooth muscle cells. Smooth muscle cells were increased in lesions containing massive extracellular lipid, more so in those having, in addition, a thrombotic component; smooth muscle cells with massive basement membranes occurred in advanced lesions. Macrophages and macrophage foam cells were the cells that increased intimal cellularity at the onset of lesions. Other cell types associated with lesions were lymphocytes, mast cells, and plasma cells, but all of these were less numerous than either smooth muscle cells or macrophages. From birth, intima was always thicker opposite the flow divider wall of a bifurcation (eccentric thickening). When atherosclerotic lesions of any type were present in coronary arteries, the amount of lipid and accompanying cell reactions were greatest in eccentric thickening; intermediate lesions and atheroma were present only in eccentric thickening while fibroatheroma often extended beyond eccentric thickening.


Cross-cultural analysis for conceptual understanding: English and Spanish perspectives.
Culture and primary language provides the context for understanding between the patient and the nurse and therefore is part of the foundation for nursing care. Knowledge development in nursing is predicated on mutual understanding and interpretation of language. Concept development has been identified as one of the approaches to the development of nursing knowledge. Since the process of concept analysis is based on understanding a phenomenon through language and experiences, this process is culture-bound and language-specific. The purpose of this column is to discuss the value of interviews with people from two different cultures resulting in an attempt to develop nursing knowledge with international relevance. An example of an analysis of a concept, worry, is provided, and the effects of culture and language on this nursing concept are discussed. The analysis was the result of collaboration among nurses from Mexico and the United States of America.


The genetics of urinary tract malformations.
In this discussion I have excluded consideration of the genetics of purely renal malformations, such as polycystic kidneys, and of functional disorders of the kidney. Systematic family studies are available for renal agenesis, duplication of the ureters, vesico-ureteric reflux (each probably due to maldevelopment of the ureteric bud), bladder exstrophy and hypospadias as isolated malformations. Renal agenesis has a birth frequency of about 1.2 in 10 000 and the proportion affected of sibs is about 3 per cent. Duplication of the ureter has a birth frequency of about 1 per cent and the proportion affected of sibs and parents of probands is about 12 per cent. Vesico-ureteral reflux also has a prevalence in early childhood of about 1 per cent and the proportion of sibs affected is about 10 per cent. Bladder exstrophy has a birth frequency of about 1 in 20 000 and perhaps about 1 per cent of sibs are affected. Hypospadias has a birth frequency in boys of about 1 in 300 and the proportion affected of brothers is about 10 per cent. Further family studies are needed of these malformations when they occur in isolation. Either the multifactorial threshold model or dominant inheritance with reduced penetrance and varied expressivity would fit the data available.


Teaching with Big Data: Report from the 2016 Society for Neuroscience Teaching Workshop.
As part of a series of workshops on teaching neuroscience at the Society for Neuroscience annual meetings, William Grisham and Richard Olivo organized the 2016 workshop on "Teaching Neuroscience with Big Data." This article presents a summary of that workshop. Speakers provided overviews of open datasets that could be used in teaching undergraduate courses. These included resources that already appear in educational settings, including the Allen Brain Atlas (presented by Joshua Brumberg and Terri Gilbert), and the Mouse Brain Library and GeneNetwork (presented by Robert Williams). Other resources, such as NeuroData (presented by William R. Gray Roncal), and OpenFMRI, NeuroVault, and Neurosynth (presented by Russell Poldrack) have not been broadly utilized by the neuroscience education community but offer obvious potential. Finally, William Grisham discussed the iNeuro Project, an NSF-sponsored effort to develop the necessary curriculum for preparing students to handle Big Data. Linda Lanyon further elaborated on the current state and challenges in educating students to deal with Big Data and described some training resources provided by the International Neuroinformatics Coordinating Facility. Neuroinformatics is a subfield of neuroscience that deals with data utilizing analytical tools and computational models. The feasibility of offering neuroinformatics programs at primarily undergraduate institutions was also discussed.


Sequence effects on peptide assembly characteristics observed by using scanning tunneling microscopy.
Homogeneous assemblies of the model peptides at interfaces have been achieved and observed with scanning tunneling microscopy. The dependence of the observed brightness in STM images is analyzed, and the correlation with the peptide residues is proposed. We have also investigated the conformational dynamics of the peptide assemblies adsorbed on a graphene sheet by performing all-atom molecular dynamic simulations in water at 300 K. The simulation results of the two peptide assemblies on graphite surfaces show that R(4)G(4)H(8) and F(4)G(4)H(8) peptide assemblies are mostly in β-sheet structure, and the interaction energy of the four different residues with graphite surfaces follows the order of Phe > His > Arg > Gly, consistent with their brightness contrasts in STM images. The insight on the distribution of residue moieties in the peptide assemblies could provide beneficial venues for studying peptide-based interfacial processes such as site-specific interactions between molecular species with peptides.


Spectral analysis during sinus rhythm predicts an abnormal atrial substrate in patients with paroxysmal atrial fibrillation.
Regions of rapid and multiple deflections can be identified with high dominant frequency (DF) during sinus rhythm (SR). These areas may play a role in the perpetuation of atrial fibrillation (AF) and indicate an atrial substrate abnormality. The purpose of this study was to investigate the atrial substrate properties of the high-frequency sites in patients with paroxysmal AF. Forty patients (52 +/- 12 years of age) with paroxysmal AF were studied using a three-dimensional mapping system. Spectral analysis was performed on the bipolar electrograms in the left atrium (LA) during SR. Overall, 7708 electrograms were analyzed, and the DFs higher than 70 Hz were labeled as abnormal. The regional distribution of the high-DF sites in the LA could be divided into two types. Type 1 includes high-DF sites existing only in the pulmonary veins (PVs; n = 19, 6.6 +/- 3.4 sites/patient). Type 2 includes high-DF sites in the LA or LA plus the PVs (n = 21, 11 +/- 5.6 sites/patient). In type 1, PV isolation (PVI) could eliminate the AF with negative AF inducibility testing after the PVI in 89% of patients. In type 2, additional LA substrate modification was needed in 81% of patients because sustained AF was induced after the PVI (P<.001, compared with type 1). Multivariate analysis showed that the lower mean voltage of the LA and high-frequency sites distribution both independently predicted a positive AF inducibility after the PVI (P<.05). Spectral analysis during SR can detect an abnormal atrial substrate. A regional distribution of the high-DF sites predicts the efficacy of the PVI.


[XXI Moscow scientific and practical conference "Otorhinolaryngology: traditions and modernity", dedicated to the 100th anniversary of the birth of Professor Nina Petrovna Konstantinova].
XXI Moscow scientific and practical conference "Otorhinolaryngology: traditions and modernity", dedicated to the 100th anniversary of the birth of Professor Nina Petrovna Konstantinova.


Construct validity-Current issues and recommendations for future hand hygiene research.
Health care-associated infection is a leading cause of morbidity and mortality. Hand hygiene is widely regarded as an effective prevention strategy. Often, hand hygiene research is designed and conducted by health care practitioners who may lack formal training in research methods, particularly in the area of social science. In a research context, a construct is a concept that can be measured or observed in some way. A construct can be directly or indirectly measured. For example, height can be directly measured by centimeters, whereas depression can be indirectly measured by a scale of 20 items. Every construct needs to be operationalized by measure(s) to make it a variable. Hence, construct validity refers to the degree of fit between the construct of interest and its operational measure. However, issues with construct validity often weaken the translation from construct to measure(s). This article will (1) describe the common threats to construct validity pertaining to hand hygiene research, (2) identify practical limitations in current research design, and (3) provide recommendations to improve construct validity in future hand hygiene research. By understanding how construct validity may affect hand hygiene research design, there is great potential to improve the validity of future hand hygiene research findings.


Interaction of staphylococcal alpha-toxin with artificial and natural membranes.
Comparison of hemolytic activity and chromate-releasing activity of partially purified preparations of staphylococcal alpha-toxin indicated the presence of a lytic factor other than alpha-toxin. This lytic release factor (RF) was isolated from the preparations and was shown to be active against both lipid spherules and erythrocytes. Heat-purified alpha-toxin (HP alpha-toxin) disrupted spherules, with the formation of fragments which always showed the presence of ring structures similar in dimensions (ca. 90 A) to pure alpha 12S-toxin. The interaction of HP alpha-toxin with spherules was accompanied by loss of hemolytic activity and adsorption of toxic protein. The alpha 12S-toxin, although only weakly hemolytic, was shown to be lytic for spherules. An alpha 12S-free toxin rapidly disrupted spherules, with formation of fragments with attached rings similar in dimensions to the alpha 12S molecule. Lipid monolayer experiments showed that HP alpha-toxin could penetrate lipid monolayers by virtue of a hydrophobic interaction. Effects of HP alpha-toxin on rabbit and human erythrocyte ghosts were similar to its effects on spherules, in that rings appeared on membrane fragments. Toxin-lysed rabbit erythrocytes showed similar rings on the resulting membrane fragments. However, rings were not seen on toxin-treated rabbit erythrocytes in the prelytic lag phase; this result and the fact that human erythrocytes are largely insensitive to alpha-toxin were interpreted as evidence against a lytic mechanism involving ring formation as the primary event. Rings were interpreted as toxin polymers similar to alpha 12S molecules, formed from specifically orientated active toxin molecules at the surface of lipid structures. Possible mechanisms for toxin lysis of spherules and erythrocytes are discussed.


Chromosome banding homologies in Swamp and Murrah buffalo.
Silver staining of Swamp buffalo (2n = 48) metaphase chromosomes revealed telomeric nucleolus organizer regions (NOR's) located on five pairs of autosomes identified by R-banding as numbers 4 p (submetacentric), 8, 20, 22, and 23 (acrocentrics); interphase nuclei also showed no more than five nucleoli. The Murrah buffalo (2n = 50) was previously reported to have telomeric NOR's located on six pairs, -3 p and 4 p (submetacentric), 8, 21, 23, and 24 (acrocentrics). By comparing the two types of buffalo it was concluded that: all of the chromosomes are similar in banding patterns; chromosome 1 of Swamp results from a telomere-centromere tandem fusion between two chromosomes identified as 4 p and 9, respectively, in the Murrah karyotype, thus accounting for the reduced diploid number of Swamp buffalo; the fusion causes the loss of NOR's on the telomeres of chromosome 4, thus accounting for the reduced number of NOR chromosome pairs of Swamp; the presence of a pale C-band are in the region of junction between chromosome 4 and 9 involved in the fusion suggests that the centromeric region of the later is retained and altered.


Intensifying action to address HIV and tuberculosis in Mozambique's cross-border mining sector.
The southern provinces of Mozambique have some of the world's highest recorded levels of HIV and tuberculosis (TB). They are also characterized by high levels of cross-border migration, particularly to mines in South Africa. Through the Declaration on Tuberculosis in the Mining Sector in August 2012, heads of state of the Southern African Development Community showed an increased commitment to addressing TB and HIV among migrant mine workers, but there is much left to do. This article analyzes the importance of recent policy developments, both regional and national. We report new research from 2011-2012 on health-related attitudes and behaviors of Mozambican mine workers and their families and present an estimate of the financial burden of disease related to migrant mine work for Mozambique's public services and migrant-sending communities. We recommend that the Declaration be operationalized and enforced. Practical measures should include training of health workers in migrants' right to health; user-friendly health information in Portuguese and local languages; building the advocacy capacity of mine workers' representatives; and more attention to social, cultural, and economic factors that affect migrant mine workers' health, including better access to health information and services and livelihoods for wives, widows, and orphans in communities of origin.


Shear stress variation induced by red blood cell motion in microvessel.
We simulated red blood cells flowing in microvessel to examine the induced wall shear stress variation. A typical peak-valley-peak structure is observed, and it is analyzed in terms of its magnitude, spatial influencing range, and temporal elapsed duration. Effects of red cell deformability, microvessel size, and flow velocity have been investigated. The corresponding variation characters have also been related to cell deformation and flow field. Simulation results show that the variation magnitude is mainly determined by the gap size between cell and vessel wall, while the spatial range of the shear stress variation depends on the cell length as well as the microvessel size. For a certain point on the vessel wall, the shear stress variation lasts a short time at a higher flow velocity, and vice versa. As the cell concentration in the microvessel increases, the shear stress variation structure changes accordingly with the two peaks from two close cells merging together, and eventually only one peak is observed at a hematocrit of 30.72%. However, the effect of hematocrit on the variation magnitude of shear stress is less obvious, and the dynamic nature of shear stress is still significant. This represents the first attempt to study the dynamic shear stress variation on microvessel as red blood cells flow by, and the information obtained in this study could be valuable to relevant research, for example, the mechanotransduction in the endothelia glycocalyx layer.


Effect of Sn Addition on Microstructure and Corrosion Behavior of As-Extruded Mg-5Zn-4Al Alloy.
The effect of Sn addition on the microstructure and corrosion behavior of extruded Mg-5Zn-4Al-xSn (0, 0.5, 1, 2, and 3 wt %) alloys was investigated by optical microscopy (OM), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), electrochemical measurements, and immersion tests. Microstructural results showed that the average grain size decreased to some degree and the amount of precipitates increased with the increasing amount of Sn. The extruded Mg-5Zn-4Al-xSn alloy mainly consisted of α-Mg, Mg32(Al,Zn)49, and Mg2Sn phases as the content of Sn was above 1 wt %. Electrochemical measurements indicated that the extruded Mg-5Zn-4Al-1Sn (ZAT541) alloy presented the best corrosion performances, with corrosion potential (Ecorr) and corrosion current density (Icorr) values of -1.3309 V and 6.707 × 10-6 A·cm-2, respectively. Furthermore, the corrosion mechanism of Sn is discussed in detail.


Recurrent invasive pneumococcal disease in individuals with human immunodeficiency virus infection.
The proportion of relapses and reinfections that are potentially preventable by vaccine in human immunodeficiency virus (HIV)-infected persons with recurrent pneumococcal disease is unknown. Isolates from HIV-infected individuals from Baltimore with recurrent pneumococcal invasive disease were collected from 1 January 1995 through 31 December 2000. Serotyping and pulsed-field gel electrophoresis were performed. From 1 January 1995 through 31 December 1998, 14.9% (404/2717) of those who had a pneumococcal infection were HIV infected. The recurrence rate among HIV-infected individuals was 6.4-fold higher than that among individuals without HIV infection (P<.01). Among recurrent infections in 41 individuals, there were 42 reinfections and 6 relapses. All relapses and 91% (70/77) of reinfections were due to serotypes covered by the 23-valent pneumococcal polysaccharide vaccine. Reinfection was more common than relapse among HIV-infected individuals with recurrent pneumococcal disease. Although a substantial proportion of recurrent pneumococcal infections was potentially preventable by vaccine, creating an effective vaccine may be challenging for this population.


Neonatal ovarian cysts: sonographic-pathologic correlation.
The authors reviewed the prenatal (11 infants) and postnatal (17 infants) sonograms and the clinical, surgical, and pathologic findings in 17 infants with an ovarian cyst to determine the sonographic features and natural history of neonatal ovarian cysts. An uncomplicated cyst (nontwisted, nonhemorrhagic) was completely anechoic and the cyst wall was imperceptible with sonography (five cases). A twisted or hemorrhagic cyst was cystic with a fluid-debris level, cystic with a retracting clot, septated with or without internal echoes, or solid (12 cases). These complicated cysts contained liquid and/or organized hematoma. Eleven of the 12 complicated cysts had a thin, highly echogenic wall. Cyst torsion commonly occurred in utero and could be diagnosed on prenatal sonograms by a typical sonographic appearance (eight cases). All of these infants were asymptomatic after birth. Four infants with hemorrhagic or twisted cysts were symptomatic. All cysts except one that resolved spontaneously were treated surgically, including three twisted cysts that showed no change in size over a 1-8-month interval. All of the cysts were of follicular origin.


Evaluation of the Negative Predictive Value of Methicillin-Resistant Staphylococcus aureus Nasal Swab Screening in the Medical Intensive Care Units and Its Effect on Antibiotic Duration.
In addition to active surveillance of methicillin-resistant Staphylococcus aureus (MRSA) carrier, MRSA nasal screening can be valuable for antibiotic de-escalation. This study aimed to assess the correlations between the MRSA nasal swab and subsequent culture results in patients admitted to medical intensive care units (MICU). The impact of MRSA nasal swab on the antibiotic duration was also evaluated. This retrospective study enrolled patients who received glycopeptides in the MICU of a medical center in 2019. Patients treated with glycopeptides for over 2 days before MICU admission were excluded. The associated data were collected through the electronic medical record system. The negative predictive value (NPV) of MRSA nasal swabs for MRSA infection was calculated, and their influence on empirical glycopeptide treatment duration was analyzed. Of the 338 patients who met the inclusion criteria, 277 underwent MRSA nasal screening. The NPV of MRSA-negative nasal swab for subsequent MRSA infection was 98.4%. The glycopeptide treatment duration of the patients with and without nasal screening was not significantly different (4.2 ± 2.8 vs 4.4 ± 3.0 days, p = 0.577). Of the 120 patients with MRSA-negative nasal swab and no subsequent MRSA infection, 75 continued empirical glycopeptides therapy. The additional treatment time was 3 days (interquartile range: 2-6 days). The MRSA nasal swabs have high NPV for MRSA infection in critically ill patients. However, it has no impact on the empirical glycopeptide treatment duration. The value of MRSA nasal swabs should be advocated to optimize antibiotic therapy.


Maternal Dietary Patterns and Gestational Diabetes Risk: A Case-Control Study.
Maternal dietary patterns play an important role in the progress of gestational diabetes mellitus (GDM). The aim of the present study was to explore this association. A total of 388 pregnant women (122 case and 266 control) were included. Dietary intake were collected using a food frequency questionnaire (FFQ). GDM was diagnosed using a 100-gram, 3-hour oral glucose tolerance test. Dietary pattern was identified by factor analysis. To investigate the relation between each of the independent variables with gestational diabetes, the odds ratio (OR) was calculated. Western dietary pattern was high in sweets, jams, mayonnaise, soft drinks, salty snacks, solid fat, high-fat dairy products, potatoes, organ meat, eggs, red meat, processed foods, tea, and coffee. The prudent dietary pattern was characterized by higher intake of liquid oils, legumes, nuts and seeds, fruits and dried fruits, fish and poultry whole, and refined grains. Western dietary pattern was associated with increased risk of gestational diabetes mellitus before and after adjustment for confounders (OR = 1.97, 95% CI: 1.27-3.04, OR = 1.68, 95% CI: 1.04-2.27). However, no significant association was found for a prudent pattern. These findings suggest that the Western dietary pattern was associated with an increased risk of GDM.


Effects of feeding blends of grains naturally contaminated with Fusarium mycotoxins on performance, metabolism, hematology, and immunocompetence of ducklings.
Experiments were conducted to determine the effects of feeding grains naturally contaminated with Fusarium mycotoxins on performance, metabolism, hematology, and immune competence of ducklings. Four hundred sixty-four 1-d-old White Pekin male ducklings were fed starter (0 to 2 wk), grower (3 to 4 wk), and finisher (5 to 6 wk) diets formulated with uncontaminated grains, a low level of contaminated grains, a high level of contaminated grains, or the higher level of contaminated grains + 0.2% polymeric glucomannan mycotoxin adsorbent. Body weight gains, feed consumption, and feed efficiency were not affected by diet. However, consumption of contaminated grains decreased plasma calcium concentrations after 2 wk and plasma uric acid concentrations at the 4-wk assessment point. Mean corpuscular hemoglobin concentrations and hematocrit decreased when ducks were fed contaminated grains for 4 or 6 wk, respectively. In contrast, total numbers of white blood cells and lymphocytes increased transiently in birds fed contaminated grains for 4 wk. The antibody response to sheep red blood cells (CD4+ T cell dependent) and the cell-mediated response to phytohemagglutinin-P (also CD4+ T cell dependent) were not affected by diet, but consumption of contaminated grains for 6 wk decreased the duration of peak cell-mediated response to dinitrochlorobenzene (CD8+ T cell dependent) assessed in a skin test. Feeding grains naturally contaminated with Fusarium mycotoxins, even at levels widely regarded as high, exerted only minor adverse effects on plasma chemistry and hematology of ducklings, and production parameters were unaffected in this avian species. Mycotoxin-contaminated feeds may, however, render these animals susceptible to infectious agents such as viruses against which the CD8+ T cell provides necessary defence. Glucomannan mycotoxin adsorbent was not effective in preventing alterations caused by Fusarium mycotoxins.


Molecular characterization of a cloned human oxytocin receptor.
We describe here the binding and functional properties of a cloned human oxytocin receptor (OTR). We established a transient OTR expression system on COS-1 cells, which do not express vasopressin receptors. With the transfected cells and [3H]oxytocin, the dissociation constant (Kd) of OTR to oxytocin was 6.0 +/- 1.1 nmol/l; the binding properties of several oxytocin-related peptides were also examined. The functional properties of OTR were determined by an electrophysiological method, using a Xenopus laevis oocyte injected with in vitro transcribed OTR mRNA. These two methods showed that [Phe2,Orn8]vasotocin, a vasopressin agonist, was an OTR antagonist. A combination of these methods using cloned OTR cDNA is a novel and effective method for the investigation of oxytocin-related ligands.


The contribution of endocervical smears to cervical cancer detection.
Data from a Colposcopy Clinic have been presented in which endocervical and cervical smears were evaluated in singly and in combination for accuracy and effectiveness. In patients with marked dysplasia, carcinoma in situ and early invasive cancer, false negative results rarely occurred using either cervical or endocervical smears; more false negatives were encountered in the minimal to moderate dysplasia group of lesions. Endocervical smears were found to be unreliable in determining the distribution of cervical neoplasia when correlated with endocervical curettage specimens. These smears contributed little as supplemental screening procedures for early cervical neoplasia since less procedures for early cervical neoplasia since less than three per cent of lesions would have been missed had only a cervical scrape smear been performed. It should be pointed out, however, that this was a young population in which cervical eversion with exposure of endocervical tissue and the neoplastic lesions was the rule. The accuracy of endocervical aspiration and endocervical swab techniques was similar although there was a much higher proportion of unsatisfactory specimens with the dry cotton swab technique.


Sutureless coronary anastomosis with an anastomotic device and tissue adhesive in off-pump porcine coronary bypass grafting.
In the search for a facilitated coronary artery anastomosis, we assessed the feasibility of a hybrid anastomosis technique that used a prototype anastomotic device with an extraluminal frame (crinoline-like) and octyl-cyanoacrylate adhesive. During off-pump coronary artery bypass grafting in pigs (n = 8), a left internal thoracic artery-right coronary artery anastomosis was constructed and evaluated during the operation and at 5 postoperative weeks. The anastomosis was examined by flow measurement, angiography, intraluminal cast geometric analysis, and histologic analysis. Anastomosis construction required 6.2 +/- 1.3 minutes (mean +/- SD). At 5 weeks all anastomoses were fully patent, with minor anastomotic diameter narrowing (median 16%, 15th-85th percentile 16%-26%). After 30-second graft occlusion, median peak hyperemic flow response was 5.0 (15th-85th percentile 4.4-6.5). As a result of complete, streamlining filling of anastomotic wall recesses by neointima formation, more intimal hyperplasia was found in the crinoline-adhesive anastomoses than in sutured control anastomoses. No excessive, lumen-narrowing neointima formation was observed, however. The hybrid coronary anastomosis technique was feasible without any need for dedicated application tools. If technical improvements can be realized, the hybrid technique may provide an alternative to manual suturing.


The pharmacological actions of pempidine and its ethyl homologue.
Pempidine, and other highly active ganglion blocking agents of the polyalkylpiperidine series, were developed from tertiary alkylamines, themselves weakly active, on the hypothesis that high activity was conferred by the presence in the molecule of a sterically hindered secondary or tertiary nitrogen atom. Pempidine and its N-ethyl homologue (26539) resembled mecamylamine qualitatively. All three drugs blocked sympathetic and parasympathetic ganglia; this action was slow in onset and protracted. They blocked neuromuscular transmission, but only about one hundredth as powerfully as ganglionic transmission. They caused a fall in amplitude and rate of the isolated heart, and reduced coronary flow. They had local anaesthetic properties in one of four tests used. They caused tremor. All were well absorbed when administered orally. Pempidine was about twice as active as mecamylamine on ganglia, but only about one half to one quarter as toxic as judged by death, growth, induction of tremor, or cardiotoxicity. Compound 26539 was also quantitatively superior to mecamylamine in respect of these safety margins, but unlike pempidine or mecamylamine damaged the pituitary gland and testis when administered daily for several months. The mode of action of the three drugs is discussed: the results give tentative support for the hypothesis that their action is intracellular.


Expression of invariant chain can cause an allele-dependent increase in the surface expression of MHC class I molecules.
Invariant chain (Ii) has been shown to play a significant part in the assembly of MHC class II molecules. Ii also binds to MHC class I, although it is not known when this first occurs or whether it can affect class I assembly. Our examination of lysates of L(d)-transfected T2 cells showed that Ii bound intracellularly to folded, but not to open, forms of MHC class I. Furthermore, addition of peptides to the lysates dissociated Ii from the Ii-folded MHC class I complex. Thus, unlike other known chaperones, Ii associates only with folded, peptide-free class I molecules. To determine whether Ii can affect MHC class I transport and surface expression, we used both wild-type Ii and a mutant Ii that lacked the endosomal targeting sequence. Neither Ii nor Ii(Delta 20) increased the rate of MHC class I migration; however, Ii and (to a greater extent) Ii(Delta 20) increased cell surface expression of MHC class I. In HeLa cells, this effect was allele-specific, affecting HLA-A28 more than -B75. Ii also increased the surface expression of K(b) more than D(b) on Panc02 pancreatic adenocarcinoma cells. Neither form of Ii was detectable at the cell surface with MHC class I, indicating that Ii had exercised its effect on class I intracellularly. In total, these data suggest that Ii can bind peptide-free folded class I/beta(2)m heterodimers, but not open MHC class I heavy chains, in the endoplasmic reticulum, and that Ii can facilitate the surface expression of the MHC class I molecule.


Preparation, characterization, and in vitro/vivo studies of oleanolic acid-loaded lactoferrin nanoparticles.
Oleanolic acid (OA), a pentacyclic triterpene, is used to safely and economically treat hepatopathy. However, OA, a Biopharmaceutics Classification System IV category drug, has low bioavailability owing to low solubility (<1 μg/mL) and biomembrane permeability. We developed a novel OA nanoparticle (OA-NP)-loaded lactoferrin (Lf) nanodelivery system with enhanced in vitro OA dissolution and improved oral absorption and bioavailability. The OA-NPs were prepared using NP albumin-bound technology and characterized using dynamic light scattering, scanning electron microscopy, X-ray powder diffraction, differential scanning calorimetry, and in vitro dissolution test. The in vivo pharmacokinetics was investigated in Sprague Dawley rats using liquid chromatography-tandem mass spectrometry. OA-NPs (OA:Lf =1:6, w/w%) exhibited spherical morphology, 202.2±8.3 nm particle size, +(27.1±0.32) mV ζ potential, 92.59%±3.24% encapsulation efficiency, and desirable in vitro release profiles. An effective in vivo bioavailability (340.59%) was achieved compared to the free drug following oral administration to rats. The Lf novel nanodelivery vehicle enhanced the dissolution rate, intestinal absorption, and bioavailability of OA. These results demonstrate that Lf NPs are a new strategy for improving oral absorption and bioavailability of poorly soluble and poorly absorbed drugs.


Pathological features of the placenta in fetal death.
Few studies of the histopathological features of the placenta in cases of fetal death are available. We will describe the placental findings from 24 midtrimester spontaneous abortions and 54 stillborn infants of more than 28 weeks' gestation. In almost 100% of midtrimester abortions and in 48% of the placentas from stillborn infants of more than 28 weeks' gestation, chorioamnionitis, deciduitis, and/or villitis were present. Because of this very high percentage of lesions, which suggests an infectious causation, it is mandatory that studies be performed that might identify pathogens. One third of the stillborn infants of more than 28 weeks' gestation were associated with maternal complications (diabetes, preeclampsia, and urinary tract infection), in addition to placental fetal vasculopathy, ischemia, infarcts, and chorangiosis (villous capillary hyperplasia). We emphasize the use of the placenta for the recognition of maternal diabetes.


Association of spinal deformity and vaccine-induced abdominal lesions in harvest-sized Atlantic salmon, Salmo salar L.
Spinal deformities in Atlantic salmon, Salmo salar L., have been described as a disease of multifactorial origin for which vaccines and time of vaccination have been suggested as risk factors. A vaccine efficacy trial where spinal deformity became evident was continued by the observational study reported here. In the preharvest part of the study 17 months post-sea transfer, there was a prevalence of 11.3% spinal deformity, with deformities present only in one vaccine group indicating a strong vaccine involvement. At slaughter, the prevalence of spinal deformities was 11.7%, and deformed fish had only 62% of normal slaughter weight. Visual analogue scales (VAS) were used for continuous recordings of vaccine-induced abdominal lesions and deformity. A logistic regression model associating presence of spinal deformity with markers of abdominal lesions was developed. The odds ratio for spinal deformity was 5.7 (95% CI: 3.4-9.4) for each unit increase in adhesion score (0-6) and 4.9 (2.9-3.4) for each unit increase in melanin on abdominal organs (0-3). Lesions in the dorsal caudal part of the abdomen gave an odds ratio for spinal deformity of 2.2.


How nerve growth factor drives physiological and inflammatory expressions of acid-sensing ion channel 3 in sensory neurons.
Nerve growth factor (NGF) is a key element of inflammatory pain. It induces hyperalgesia by up-regulating the transcription of genes encoding receptors, ion channels, and neuropeptides. Acid-sensing ion channel 3 (ASIC3), a depolarizing sodium channel gated by protons during tissue acidosis, is specifically expressed in sensory neurons. It has been associated to cardiac ischemic and inflammatory pains. We previously showed that low endogenous NGF was responsible for ASIC3 basal expression and high NGF during inflammation increased ASIC3 expression parallely to the development of neuron hyperexcitability associated with hyperalgesia. NGF is known to activate numerous signaling pathways through trkA and p75 receptors. We now show that (i). NGF controls ASIC3 basal expression through constitutive activation of a trkA/phospholipase C/protein kinase C pathway, (ii). high inflammatory-like NGF induces ASIC3 overexpression through a trkA/JNK/p38MAPK pathway and a p75-dependent mechanism as a transcriptional switch, and (iii). NGF acts through AP1 response elements in ASIC3 encoding gene promoter. These new data indicate potential targets that could be used to develop new treatments against inflammatory pain.


Discriminative Training of Deep Fully Connected Continuous CRFs With Task-Specific Loss.
Recent works on deep conditional random fields (CRFs) have set new records on many vision tasks involving structured predictions. Here, we propose a fully connected deep continuous CRF model with task-specific losses for both discrete and continuous labeling problems. We exemplify the usefulness of the proposed model on multi-class semantic labeling (discrete) and the robust depth estimation (continuous) problems. In our framework, we model both the unary and the pairwise potential functions as deep convolutional neural networks (CNNs), which are jointly learned in an end-to-end fashion. The proposed method possesses the main advantage of continuously valued CRFs, which is a closed-form solution for the maximum a posteriori (MAP) inference. To better take into account the quality of the predicted estimates during the cause of learning, instead of using the commonly employed maximum likelihood CRF parameter learning protocol, we propose task-specific loss functions for learning the CRF parameters. It enables direct optimization of the quality of the MAP estimates during the learning process. Specifically, we optimize the multi-class classification loss for the semantic labeling task and the Tukey's biweight loss for the robust depth estimation problem. Experimental results on the semantic labeling and robust depth estimation tasks demonstrate that the proposed method compare favorably against both baseline and state-of-the-art methods. In particular, we show that although the proposed deep CRF model is continuously valued, with the equipment of task-specific loss, it achieves impressive results even on discrete labeling tasks.


Risk of ischemic stroke after an acute myocardial infarction in patients with diabetes mellitus.
Incidence, any trend over time, and predictors of ischemic stroke after an acute myocardial infarction (AMI) in diabetic patients are unknown. Data for 173,233 unselected patients with an AMI, including 33,503 patients with diabetes mellitus, were taken from the Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA) during 1998 to 2008. Ischemic stroke events were recorded during 1 year of follow-up. Patients with diabetes mellitus more often had a history of cardiovascular disease, received less reperfusion therapy, and were treated with acetylsalicylic acid, P2Y12 inhibitors, and statins to a lesser extent compared with patients without diabetes mellitus. However, the use of evidence-based therapies increased markedly in both groups during the study period. The incidence of ischemic stroke during the first year after AMI decreased from 7.1% to 4.7% in patients with diabetes mellitus and from 4.2% to 3.7% in patients without diabetes mellitus. Risk reduction was significantly larger in the diabetic subgroup. Reperfusion therapy, acetylsalicylic acid, P2Y12 inhibitors, and statins were independently associated with the reduced stroke risk. Ischemic stroke is a fairly common complication after an AMI in patients with diabetes mellitus, but the risk of stroke has decreased during recent years. The increased use of evidence-based therapies contributes importantly to this risk reduction, but there is still room for improvement.


Draft Genome Sequence of Paenibacillus sp. Strain MY03, a Terrestrial Bacterium Capable of Degrading Multiple Marine-Derived Polysaccharides.
The bacterium Paenibacillus sp. strain MY03, isolated from the root soil of cypress, can effectively degrade marine-derived polysaccharides such as agar, alginate, and chitin. Here, we present the draft genome sequence of MY03. Putative enzymes, including 3 agarases, 1 alginate lyase, and 1 chitinase, were found.


Keratoacanthoma: a distinct entity?
Keratoacanthoma (KA) are common but exceptional benign tumors, often appearing on sun-exposed areas of light skinned people and showing spontaneous resolution. The goal of this study was to review existing literature, to point out the etiological complexity of KA biology and to answer the controversial debate if or not KA is a distinct entity or a variant of squamous cell carcinoma (SCC). Relying on recent results, we highlight that KA is an individual lesion with a unique molecular signature caused by alterations in the TGFβ signalling pathway. These recent findings will help to understand the nature of KA and to develop new reliable diagnostic tools, simplifying the discrimination of the histologically similar KA and SCC.