Diagnostic tests and biomarkers for pheochromocytoma and extra-adrenal paraganglioma: from routine laboratory methods to disease stratification.
The laboratory workup of patients with pheochromocytoma and extra-adrenal paraganglioma (PPGLs) has traditionally focused on biochemical measurements of tumor secretory products or their metabolites, with ultimate diagnosis resting on routine histopathology and immunohistochemistry. While such testing remains important, the needs to distinguish potentially metastatic from benign tumors and to identify tumors with a hereditary basis have stimulated searches for additional means to stratify patients according to risk of metastasis or presence of a particular mutation. Biomarkers based on traditional biochemical tests, such as profiles of catecholamine metabolites and granin-derived peptides, provide utility for both purposes, while novel biomarkers are being identified by proteomic and transcriptomic studies, the latter including microRNA expression profiling. Histopathological scoring methods for predicting metastatic potential, such as the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS), are limited by poor interobserver concordance, discrepant results between studies and incomplete knowledge of how scores relate to genotype. Immunohistochemical staining for succinate dehydrogenase (SDH) subunit B to triage patients for genetic testing of SDH subunit genes illustrates the growing importance of pathology as an adjunct to genetic testing for disease stratification. Although considerable effort has been expended on microarray-based platforms to identify biomarkers of malignancy, as yet, none of those proposed have been demonstrated to reliably discriminate malignant from benign disease any better than the PASS. Because of the heterogeneity of PPGLs and variable time between first appearance of tumors and identification of metastases, any prospective study to establish prognostic efficacy requires large numbers of patients and extended follow-up.


Mouth breathing compromises adherence to nasal continuous positive airway pressure therapy.
Mouth leak compromises nasal continuous positive airway pressure (CPAP) therapy. We hypothesized that patients who breathe mainly through their mouths during sleep, compared to those who breathe mainly through their noses, would have more mouth leak during CPAP and therefore lower adherence to CPAP. A case-control study to compare adherence to CPAP at 1 year in mouth breathers (MBs) with nose breathers (NBs). University teaching hospital with a sleep laboratory. Fifty-one CPAP-naive patients (4 women), with a respiratory disturbance index (RDI) > 15/h. Of the 51 patients, 30 patients breathed through their mouths (mouth breathing > 70% of total sleep time [TST]), and 21 patients breathed through their noses (mouth breathing < 30% of TST). MBs between 30% and 70% of TST were excluded. Overnight polysomnography was performed at baseline, during CPAP titration, and at 3 months. Patients were followed up for 1 year after beginning CPAP. To measure mouth breathing, nasal and oral thermistors during polysomnography were separated by a 3 x 6-cm silicon transverse diaphragm. RDI decreased from (mean +/- SD) 37.8 +/- 21.5 to 1.8 +/- 2.6/h at 3 months. Throughout the study, adherence to CPAP (mean daily CPAP use in hours) was better in NBs. Most NBs (71%) but only 30% of MBs used CPAP daily for > 4 h at 1-year follow-up. Mouth breathing decreased significantly from 84 +/- 8.9% at baseline to 22 +/- 14.4% at 3 months. Patients with moderate-to-severe sleep-disordered breathing and a high percentage of mouth breathing during sleep were less adherent to CPAP therapy than patients exhibiting a low percentage of mouth breathing.


An Efficient Method for the Isolation of Highly Purified RNA from Seeds for Use in Quantitative Transcriptome Analysis.
Plant seeds accumulate large amounts of storage reserves comprising biodegradable organic matter. Humans rely on seed storage reserves for food and as industrial materials. Gene expression profiles are powerful tools for investigating metabolic regulation in plant cells. Therefore, detailed, accurate gene expression profiles during seed development are required for crop breeding. Acquiring highly purified RNA is essential for producing these profiles. Efficient methods are needed to isolate highly purified RNA from seeds. Here, we describe a method for isolating RNA from seeds containing large amounts of oils, proteins, and polyphenols, which have inhibitory effects on high-purity RNA isolation. Our method enables highly purified RNA to be obtained from seeds without the use of phenol, chloroform, or additional processes for RNA purification. This method is applicable to Arabidopsis, rapeseed, and soybean seeds. Our method will be useful for monitoring the expression patterns of low level transcripts in developing and mature seeds.


Jointly modeling the relationship between longitudinal and survival data subject to left truncation with applications to cystic fibrosis.
Numerous methods for joint analysis of longitudinal measures of a continuous outcome y and a time to event outcome T have recently been developed either to focus on the longitudinal data y while correcting for nonignorable dropout, to predict the survival outcome T using the longitudinal data y, or to examine the relationship between y and T. The motivating problem for our work is in joint modeling of the serial measurements of pulmonary function (FEV1% predicted) and survival in cystic fibrosis (CF) patients using registry data. Within the CF registry data, an additional complexity is that not all patients have been followed from birth; therefore, some patients have delayed entry into the study while others may have been missed completely, giving rise to a left truncated distribution. This paper shows in joint modeling situations where y and T are not independent, that it is necessary to account for this left truncation to obtain valid parameter estimates related to both survival and the longitudinal marker. We assume a linear random effects model for FEV1% predicted, where the random intercept and slope of FEV1% predicted, along with a specified transformation of the age at death follow a trivariate normal distribution. We develop an expectation-maximization algorithm for maximum likelihood estimation of parameters, which takes left truncation and right censoring of survival times into account. The methods are illustrated using simulation studies and using data from CF patients in a registry followed at Rainbow Babies and Children's Hospital, Cleveland, OH.


Lateral prefrontal/orbitofrontal cortex has different roles in norm compliance in gain and loss domains: a transcranial direct current stimulation study.
Sanction is used by almost all known human societies to enforce fairness norm in resource distribution. Previous studies have consistently shown that the lateral prefrontal cortex (lPFC) and the adjacent orbitofrontal cortex (lOFC) play a causal role in mediating the effect of sanction threat on norm compliance. However, most of these studies were conducted in gain domain in which resources are distributed. Little is known about the mechanisms underlying norm compliance in loss domain in which individual sacrifices are needed. Here we employed a modified version of dictator game (DG) and high-definition transcranial direct current stimulation (HD-tDCS) to investigate to what extent lPFC/lOFC is involved in norm compliance (with and without sanction threat) in both gain- and loss-sharing contexts. Participants allocated a fixed total amount of monetary gain or loss between themselves and an anonymous partner in multiple rounds of the game. A computer program randomly decided whether a given round involved sanction threat for the participants. Results showed that disruption of the right lPFC/lOFC by tDCS increased the voluntary norm compliance in the gain domain, but not in the loss domain; tDCS on lPFC/lOFC had no effect on compliance under sanction threat in either the gain or loss domain. Our findings reveal a context-dependent nature of norm compliance and differential roles of lPFC/lOFC in norm compliance in gain and loss domains.


Multivariate Pattern Analysis Techniques for Electroencephalography Data to Study Flanker Interference Effects.
A central challenge in cognitive neuroscience is to understand the neural mechanisms that underlie the capacity to control our behavior according to internal goals. Flanker tasks, which require responding to stimuli surrounded by distracters that trigger incompatible action tendencies, are frequently used to measure this conflict. Even though the interference generated in these situations has been broadly studied, multivariate analysis techniques can shed new light into the underlying neural mechanisms. The current study is an initial approximation to adapt an interference Flanker paradigm embedded in a Demand-Selection Task (DST) to a format that allows measuring concurrent high-density electroencephalography (EEG). We used multivariate pattern analysis (MVPA) to decode conflict-related electrophysiological markers associated with congruent or incongruent target events in a time-frequency resolved way. Our results replicate findings obtained with other analysis approaches and offer new information regarding the dynamics of the underlying mechanisms, which show signs of reinstantiation. Our findings, some of which could not have been obtained with classic analytical strategies, open novel avenues of research.


Efficacy of Antimicrobial Agents for Food Contact Applications: Biological Activity, Incorporation into Packaging, and Assessment Methods: A Review.
Interest in the utilization of antimicrobial active packaging for food products has increased in recent years. Antimicrobial active packaging involves the incorporation of antimicrobial compounds into packaging materials, with the aim of maintaining or extending food quality and shelf life. Plant extracts, essential oils, organic acids, bacteriocins, inorganic substances, enzymes, and proteins are used as antimicrobial agents in active packaging. Evaluation of the antimicrobial activity of packaging materials using different methods has become a critical issue for both food safety and the commercial utilization of such packaging technology. This article reviews the different types of antimicrobial agents used for active food packaging materials, the main incorporation techniques, and the assessment methods used to examine the antimicrobial activity of packaging materials, taking into account their safety as food contact materials.


Illusory superiority and schizotypal personality: explaining the discrepancy between subjective/objective psychopathology.
An interesting paradox has emerged from the literature regarding schizotypy--defined as the personality organization reflecting a putative liability for schizophrenia--spectrum disorders. Across certain cognitive, emotional, quality of life, and other functional variables, individuals with schizotypy report experiencing relatively severe levels of pathology. However, on objective tests of these same variables, individuals with schizotypy perform largely in the healthy range. These subjective impairments are paradoxical in that individuals with schizotypy, typically recruited from undergraduate college populations, should be healthier in virtually every conceivable measure compared to chronic, older outpatients with severe mental illness. The present study evaluated the idea that the subjective deficits associated with schizotypy largely reflect a lack of illusory superiority bias-a normally occurring bias associated with an overestimation of self-reported positive qualities and underestimation of negative qualities compared to others. In the present study, both state-measured using laboratory emotion-induction methods-and trait positive and negative emotion was assessed across self (e.g., how do you feel at this moment?) and other (e.g., how do most people feel at this moment?) domains in 39 individuals with self-reported schizotypy and 39 matched controls. Controls demonstrated an illusory superiority effect across both state and trait measures whereas individuals with schizotypy did not. These results were not explained by severity of mental health symptoms. These results suggest that a cognitive bias, or lack thereof, is a marker of schizotypy and a potential target for further research and therapy.


Is generative artificial intelligence the next step toward a personalized hemodialysis?
Artificial intelligence (AI) generative models driven by the integration of AI and natural language processing technologies, such as OpenAI's chatbot generative pre-trained transformer large language model (LLM), are receiving much public attention and have the potential to transform personalized medicine. Dialysis patients are highly dependent on technology and their treatment generates a challenging large volume of data that has to be analyzed for knowledge extraction. We argue that, by integrating the data acquired from hemodialysis treatments with the powerful conversational capabilities of LLMs, nephrologists could personalize treatments adapted to patients' lifestyles and preferences. We also argue that this new conversational AI integrated with a personalized patient-computer interface will enhance patients' engagement and self-care by providing them with a more personalized experience. However, generative AI models require continuous and accurate updates of data, and expert supervision and must address potential biases and limitations. Dialysis patients can also benefit from other new emerging technologies such as Digital Twins with which patients' care can also be addressed from a personalized medicine perspective. In this paper, we will revise LLMs potential strengths in terms of their contribution to personalized medicine, and, in particular, their potential impact, and limitations in nephrology. Nephrologists' collaboration with AI academia and companies, to develop algorithms and models that are more transparent, understandable, and trustworthy, will be crucial for the next generation of dialysis patients. The combination of technology, patient-specific data, and AI should contribute to create a more personalized and interactive dialysis process, improving patients' quality of life.


Adolescent Problematic Social Networking and School Experiences: The Mediating Effects of Sleep Disruptions and Sleep Quality.
An important developmental task for adolescents is to become increasingly responsible for their own health behaviors. Establishing healthy sleep routines and controlling media use before bedtime are important for adequate, quality sleep so adolescents are alert during the day and perform well at school. Despite the prevalence of adolescent social media use and the large percentage of computers and cell phones in adolescents' bedrooms, no studies to date have investigated the link between problematic adolescent investment in social networking, their sleep practices, and associated experiences at school. A sample of 1,886 students in Australia aged between 12 and 18 years of age completed self-report data on problematic social networking use, sleep disturbances, sleep quality, and school satisfaction. Structural equation modeling (SEM) substantiated the serial mediation hypothesis: for adolescents, problematic social networking use significantly increased sleep disturbances, which adversely affected perceptions of sleep quality that, in turn, lowered adolescents' appraisals of their school satisfaction. This significant pattern was largely driven by the indirect effect of sleep disturbances. These findings suggest that adolescents are vulnerable to negative consequences from social networking use. Specifically, problematic social networking is associated with poor school experiences, which result from poor sleep habits. Promoting better sleep routines by minimizing sleep disturbances from social media use could improve school experiences for adolescents with enhanced emotional engagement and improved subjective well-being.


Genetic-background modulation of core and variable autistic-like symptoms in Fmr1 knock-out mice.
No animal models of autism spectrum disorders (ASD) with good construct validity are currently available; using genetic models of pathologies characterized by ASD-like deficits, but with known causes, may be therefore a promising strategy. The Fmr1-KO mouse is an example of this approach, modeling Fragile X syndrome, a well-known genetic disorder presenting ASD symptoms. The Fmr1-KO is available on different genetic backgrounds (FVB versus C57BL/6), which may explain some of the conflicting results that have been obtained with these mutants up till now. Fmr1 KO and their wild-type littermates on both the FVB and C57BL/6 genetic backgrounds were examined on a battery of tests modeling the clinical symptoms of ASD, including the triad of core symptoms (alterations in social interaction and communication, presence of repetitive behaviors), as well as the secondary symptoms (disturbances in sensori-motor reactivity and in circadian patterns of activity, epileptic events). Fmr1-KO mice displayed autistic-like core symptoms of altered social interaction and occurrence of repetitive behaviors with additional hyperactivity. The genetic background modulated the effects of the Fmr1 deletion and it appears that the C57BL/6 background may be more suitable for further research on core autistic-like symptoms. The Fmr1-mouse line does not recapitulate all of the main core and secondary ASD symptoms, but still can be useful to elucidate the neurobiological mechanisms underlying specific ASD-like endophenotypes.


The Pseudomonas aeruginosa hscA gene encodes Hsc66, a DnaK homologue.
Under heat-stress conditions bacteria induce, among other heat-shock proteins, the Hsp70 molecular chaperone (DnaK), which is involved in protein stabilization. It has been shown in Escherichia coli that an Hsp70 homologue called Hsc66, which is widespread in bacteria, functions as a chaperone in vitro. This paper reports the isolation of a Pseudomonas aeruginosa W51D mutant (W51M22) by insertion of the mini-Tn5-Hg transposon, which was unable to grow on ethanol and other short-chain alcohols as sole source of carbon. The transposon insertion in this mutant was shown to be located in the hscA gene encoding Hsc66. The inability of mutant W51M22 to use ethanol was complemented by the E. coli hscBA-fdx operon. The authors characterized the transcriptional arrangement of hscA, showing that it forms part of an operon with the upstream hscB gene, and that it is also expressed from its own promoter. These results are compatible with the P. aeruginosa Hsc66 protein being a functional molecular chaperone involved in the stabilization, in the presence of ethanol, of some proteins required for bacterial growth on short-chain alcohols.


Waveform modulation of negative-pressure wound therapy in the murine model.
Negative-pressure wound therapy applied with a porous foam interface has been shown to accelerate granulation-tissue formation when a cyclic application mode of suction is applied, but the optimal waveform has not been determined. The authors hypothesized that changes in the suction waveform applied to wounds would modulate the biological response of granulation tissue formation. A vacuum-assisted closure device (Kinetic Concepts, Inc., San Antonio, Texas) was applied to full-thickness wounds in 48 male diabetic mice (C57BL/KsJ-Lepr db), which were treated with six different waveforms: square waveforms of 125 mmHg of suction for 2 minutes, alternating with 50 mmHg of suction for 2 minutes, 5 minutes, or 10 minutes; triangular waveform with a 7-minute period oscillating between 50 and 125 mmHg; and static suction at 125 mmHg or static suction at 0 mmHg (occlusive dressing). Wounds were quantitatively evaluated for granulation tissue thickness as well as the number of proliferating cells and the number of blood vessels of the newly formed granulation tissue. At 7 days, the continuous and triangular waveforms induced the thickest granulation tissue, with high rates of cellular proliferation and blood vessel counts compared with square wave and occlusive dressing control wounds. Decreasing square waveform frequency significantly increased granulation tissue thickness, cellular proliferation, and blood vessel counts. Waveform modulation has a significant effect on granulation tissue formation, angiogenesis, and cellular proliferation in excisional wounds in diabetic mice. The rapid change in pressure seen in our square wave model may be detrimental to granulation tissue formation.


The use of Skype in a community hospital inpatient palliative medicine consultation service.
Skype™, an Internet-based communication tool, has enhanced communication under numerous circumstances. As telemedicine continues to be an increasing part of medical practice, there will be more opportunities to use Skype and similar tools. Numerous scenarios in the lay literature have helped to highlight the potential uses. Although most commonly used to enhance physician-to-patient communication, there has been limited reported use of Skype for patient-to-family communication, especially in end of life and palliative care. Our inpatient Palliative Medicine Consultation Service has offered and used this technology to enhance our patients' quality of life. The objective was to provide another tool for our patients to use to communicate with family and/or friends, especially under circumstances in which clinical symptoms, functional status, financial concerns, or geographic limitations preclude in-person face-to face communication.


Effects of temperature on physiological performance and behavioral thermoregulation in an invasive fish, the round goby.
Invasive species exert negative impacts on biodiversity and ecosystems on a global scale, which may be enhanced in the future by climate change. Knowledge of how invasive species respond physiologically and behaviorally to novel and changing environments can improve our understanding of which traits enable the ecological success of these species, and potentially facilitate mitigation efforts. We examined the effects of acclimation to temperatures ranging from 5 to 28°C on aerobic metabolic rates, upper temperature tolerance (critical thermal maximum, CTmax), as well as temperature preference (Tpref) and avoidance (Tavoid) of the round goby (Neogobius melanostomus), one of the most impactful invasive species in the world. We show that round goby maintained a high aerobic scope from 15 to 28°C; that is, the capacity to increase its aerobic metabolic rate above that of its maintenance metabolism remained high across a broad thermal range. Although CTmax increased relatively little with acclimation temperature compared with other species, Tpref and Tavoid were not affected by acclimation temperature at all, meaning that round goby maintained a large thermal safety margin (CTmax-Tavoid) across acclimation temperatures, indicating a high level of thermal resilience in this species. The unperturbed physiological performance and high thermal resilience were probably facilitated by high levels of phenotypic buffering, which can make species readily adaptable and ecologically competitive in novel and changing environments. We suggest that these physiological and behavioral traits could be common for invasive species, which would only increase their success under continued climate change.


Estimation of indole-3-acetic acid in gametophytes of the moss, Physcomitrella patens.
By means of gas chromatography-selected ion monitoring-mass spectrometry using an isotope-dilution assay with 4,5,6,7-tetradeutero-indole-3-acetic acid as the internal standard, indole-3-acetic acid has been estimated to be present in aseptically cultured gametophytes of wild-type Physcomitrella patens (Hedw.) B.S.G. at a level of 0.075 μg g(-1) dry weight or 2.1 ng g(-1) fresh weight.


Emergence and characterization of serotype G9 rotavirus strains from Africa.
Serotype G9 strains have been detected sporadically and in localized outbreaks in various African countries, including South Africa, Botswana, Malawi, Kenya, Cameroon, Nigeria, Ghana, Guinea-Bissau, Libya, and Mauritius. Serotype G9 strains were analyzed to investigate genogroup characteristics, including subgroup specificity, electropherotype, and P and G genotypes. In addition, the antigenic composition of the South African G9 strains was assessed. African G9 strains were associated with both DS-1-like characteristics and Wa-like characteristics, indicating the predisposition of G9 strains to frequently reassort. Despite these reassortment events, serotype G9 strains appear to maintain antigenic character in the outer capsid protein, as evident with the reaction of the South African G9 strains with the G9-specific monoclonal antibody F45:1. Phylogenetic analysis clustered African G9 strains geographically, regardless of genogroup characteristics, into 1 lineage (IIId). Two groups of G9 strains, originating in India and Japan, were identified in this lineage. Continuous surveillance of circulating rotavirus strains in Africa is vital to prepare for future vaccine implementation on a continent that clearly needs such preventative medicines.


Liquid nitrogen in the treatment of skin diseases.
Liquid nitrogen is a satisfactory freezing agent in the treatment of such skin diseases as warts, keratoses, superficial hemangiomas, leukoplakia, keloids, superficial scarring and dermatitis venenata. It is available and easily applied. Its use is described and the results of treatment in 154 cases of warts are presented.


Cerebellar Tissue Strain in Chiari Malformation with Headache.
The pathogenesis of Chiari malformation type 1 (CM-1)-associated Valsalva headache is unknown, but it may be caused by abnormal cerebellar tonsil tissue strain. Advances in cardiac-gated magnetic resonance imaging (MRI) techniques such as balanced fast-field echo (bFFE) allow quantification of the motion of anatomic structures and can be used to measure tissue strain. The current study investigated the relationship between Valsalva heachache and tonsillar motion in patients with CM-1. A retrospective review of patients with CM-1 who had undergone cardiac-gated bFFE MRI was performed. Headache symptoms were retrieved from the medical records. Anatomic landmarks were manually selected on the cine bFFE, and a validated motion-tracking software was used to assess motion over the cardiac cycle in patients at rest. For each patient, displacement, strain, and strain rate were calculated for 3 anatomic segments. Patients undergoing surgery were examined before and after surgery. From 88 patients, a total of 108 bFFE sequences were analyzed. Valsalva headache was present in 50% of patients. Cerebellar tonsil displacement (P = 0.003), strain (P = 0.012), and maximum strain rate (P = 0.04) were reduced after surgery (n = 20). There was no statistically significant association between tissue motion and headache symptoms. The results of this study do not support a relationship between cardiac cycle cerebellar strain and Valsalva headache in patients with CM-1. It is possible that cerebellar strain related to respiratory maneuvers is associated with headache in Chiari patients. Further investigation of tissue strain is warranted because it represents a potential biomarker for outcomes after surgery.


Influence of apoptosis on neurological outcome following traumatic cerebral contusion.
Apoptosis has increasingly been implicated in the pathobiology of traumatic brain injury (TBI). The present study was undertaken to confirm the presence of apoptosis in the periischemic zone (PIZ) of traumatic cerebral contusions and to determine the role of apoptosis, if any, in neurological outcome. Brain tissue harvested at Wentworth Hospital from the PIZ in 29 patients with traumatic supratentorial contusions was compared with brain tissue resected in patients with epilepsy. Immunohistochemical analyses were performed on the tissues to see if they contained the apoptosis-related proteins p53, bcl-2, bax, and caspase-3. The findings were then correlated to demographic, clinical, surgical, neuroimaging, and outcome data. In the PIZ significant increases of bax (18-fold; p < 0.005) and caspase-3 (20-fold; p < 0.005) were recorded, whereas bcl-2 was upregulated in only 14 patients (48.3%; 2.9-fold increase) compared with control tissue. Patients in the bcl-2-positive group exhibited improved outcomes at the 18-month follow-up examination despite an older mean age and lower mean admission Glasgow Coma Scale score (p < 0.03). Caspase-3 immunostaining was increased in those patients who died (Glasgow Outcome Scale [GOS] Score 1, 12 patients) when compared with those who experienced a good outcome (GOS Score 4 or 5, 17 patients) (p < 0.005). Regression analysis identified bcl-2-negative status (p < 0.04, odds ratio [OR] 5.5; 95% confidence interval [CI] 1.1-28.4) and caspase-3-positive status (p < 0.01, OR 1.4, 95% CI 1.1-1.8) as independent predictors of poor outcome. No immunostaining for p53 was recorded in the TBI specimens. The present findings confirm apoptosis in the PIZ of traumatic cerebral contusions and indicate that this form of cell death can influence neurological outcome following a TBI.


A focus on the multiple interfaces between action and perception and their neural correlates.
Successful behaviour relies on the appropriate interplay between action and perception. The well-established dorsal and ventral stream theories depicted two distinct functional pathways for the processes of action and perception, respectively. In physiological conditions, the two pathways closely cooperate in order to produce successful adaptive behaviour. As the coupling between perception and action exists, this requires an interface that is responsible for a common reading of the two functions. Several studies have proposed different types of perception and action interfaces, suggesting their role in the creation of the shared interaction channel. In the present review, we describe three possible perception and action interfaces: i) the motor code, including common coding approaches, ii) attention, and iii) object affordance; we highlight their potential neural correlates. From this overview, a recurrent neural substrate that underlies all these interface functions appears to be crucial: the parieto-frontal circuit. This network is involved in the mirror mechanism which underlies the perception and action interfaces identified as common coding and motor code theories. The same network is also involved in the spotlight of attention and in the encoding of potential action towards objects; these are manifested in the perception and action interfaces for common attention and object affordance, respectively. Within this framework, most studies were dedicated to the description of the role of the inferior parietal lobule; growing evidence, however, suggests that the superior parietal lobule also plays a crucial role in the interplay between action and perception. The present review proposes a novel model that is inclusive of the superior parietal regions and their relative contribution to the different action and perception interfaces.


Financial influence on global risks of zoonotic emerging and re-emerging diseases: an integrative analysis.
Emerging and re-emerging infectious diseases (EIDs), such as Ebola virus disease and highly pathogenic influenza, are serious threats to human health and wellbeing worldwide. The financial sector has an important, yet often ignored, influence as owners and investors in industries that are associated with anthropogenic land-use changes in ecosystems linked to increased EIDs risks. We aimed to analyse financial influence associated with EIDs risks that are affected by anthropogenic land-use changes. We also aimed to provide empirical assessments of such influence to help guide engagements by governments, private organisations, and non-governmental organisations with the financial sector to advance a planetary health agenda. For this integrative analysis, we identified regions in the world where there was evidence of a connection between EIDs and anthropogenic land-use changes between Nov 9, 1999, and Oct 25, 2021, through a targeted literature review of academic literature and grey literature to identify evidence of drivers of anthropogenic land-use change and their association with commodity production in these regions. We only included publications in English that showed a connection between deforestation and the production of one or more commodities. Publications merely describing spatial or temporal land-use change dynamics (eg, a reduction of forest or an increase of palm-oil plantations) were excluded. As we were assessing financial influence on corporate activities through ownership specifically, we focused our analysis on publicly listed companies. Equity data and data about ownership structure were extracted from Orbis, a company information database. We assessed financial influence by identifying financial entities with the largest equity ownership, descriptively mapping transboundary connections between investors and publicly listed companies. 227 public and private companies operating in five economic sectors (ie, production of palm oil, pulp and wood products, cocoa, soybeans, and beef) between Dec 15, 2020, and March 8, 2021, were identified. Of these 227, 99 (44%) were publicly listed companies, with 2310 unique shareholders. These publicly listed companies operated in six geographical regions, resulting in nine case-study regions. 54 (55%) companies with complete geographical information were included in the countries network. Four financial entities (ie, Dimensional, Vanguard, BlackRock, and Norway's sovereign wealth fund) each had ownership in 39 companies or more in three of the case-study regions (ie, north America, east Asia, and Europe). Four large US-based asset managers (ie, Vanguard, BlackRock, T Rowe Price, and State Street) were the largest owners of publicly listed companies in terms of total equity size, with ownership amounts for these four entities ranging from US$8 billion to $21 billion. The specific patterns of cross-national ownership depended on the region of interest; for example, financial influence on EIDs risks that was associated with commodity production in southeast and east Asia came from not only global asset managers but also Malaysian, Chinese, Japanese, and Korean financial entities. India, Brazil, the USA, Mexico, and Argentina were the countries towards which investments were most directed. Although commodity supply chains and financial markets are highly globalised, a small number of investors and countries could be viewed as disproportionally influential in sectors that increase EIDs risks. Such financial influence could be used to develop and implement effective policies to reduce ecological degradation and mitigate EIDs risks and their effects on population health. Formas and Networks of Financial Rupture-how cascading changes in the climate and ecosystems could impact on the financial sector.


Effect of macrophages on phorbol ester-stimulated comitogenesis in bovine lymphocytes.
12-O-Tetradecanoylphorbol-13-acetate (TPA) added together with mitogenic lectins to bovine lymph node lymphocytes causes a synergistic increase in DNA synthesis. This comitogen effect is due to an increase in cell proliferation. To determine the role of macrophages in comitogenesis, lymphocyte preparations were depleted of macrophages by sequential adherence to glass, plastic, and nylon wool. Phagocytic cells were removed by incubation with carbonyl iron and a magnet. After macrophage depletion, the lymphocyte response to lectins decreased, indicating the accessory function of macrophages in mitogenesis. The addition of TPA or macrophages to the depleted cultures restored its response to that of the unfractionated cells. TPA was still comitogenic with lectin in lymphocyte preparations from which all residual macrophages were removed by antimacrophage serum and complement. Therefore, the comitogenic effect of TPA is independent of macrophages in these cultures.


Isolation and characterization of a tetrasialoganglioside from mouse brain, containing 9-O-acetyl,N-acetylneuraminic acid.
A new ganglioside, containing an alkali-labile linkage, was extracted from mouse brain and purified. It represents 3.6% of total lipid-bound sialic acid in the tissue and was obtained in pure form with a yield of about 35%. It contains sphingosine, glucose, galactose, N-acetylgalactosamine and sialic acid in the molar ratio 1:1:2:1:4 and, upon exhaustive sialidase treatment gives the monosialoganglioside GM1. Partial acid hydrolysis, methylation analysis, gas-liquid chromatography-mass spectrometry and chromium trioxide oxidation studies showed its basic neutral glycosphingolipid core to be ganglio-N-tetraose-ceramide. Three of the four sialic acid residues are N-acetylneuraminic acid and one, as shown by gas-liquid chromatography-mass spectrometry, is 9-O-acetyl,N-acetylneuraminic acid, which contains the alkali labile linkage. 9-O-acetyl,N-acetylneuraminic acid is ?-ketosidically linked to position 8 of the N-acetylneuraminic acid residue bound to position 3 of the internal galactose. The other two N-acetylneuraminic acid residues form a disialosyl residue linked to position 3 of external galactose. The complete structure of the studied ganglioside is as follows: NeuAc?2-8NeuAc?2-3Gal?1-3GalNAc?1-4(9-O-Ac-NeuAca?2-8NeuAc?2-1?-N-acylsphingosine, and it can be considered as a derivative of the tetrasialoganglioside GQ1b.


Effects of mindfulness, reappraisal, and suppression on sad mood and cognitive resources.
The present study investigated the relative effects of mindfulness, reappraisal and suppression in reducing sadness, and the extent to which implementation of these strategies affects cognitive resources in a laboratory context. A total of 171 Singaporean undergraduate participants were randomly assigned to receive brief training in mindfulness, reappraisal, or suppression prior to undergoing a sad mood induction. Individual adherence to Asian cultural values was assessed as a potential moderator of strategy effectiveness. Participants rated their mood and completed a Color-Word Stroop task before and after mood regulation instructions. Analyses using multi-level modelling showed that the suppression condition caused less robust declines in sadness over time compared to mindfulness. There was also a nonsignificant trend in which mindfulness was associated with greater sadness recovery compared to reappraisal. Suppression resulted in lower average sadness compared to mindfulness among those high on Asian cultural values, but not those low on Asian cultural values. Both mindfulness and reappraisal buffered against increases in Stroop interference from pre-to post-regulation compared to suppression. The findings highlight the advantage of mindfulness as a strategy effective not only in the regulation of sad mood, but also in the preservation of cognitive resources in the context of mood regulation.


Prevalence and incidence of acute and chronic comorbidity in patients with squamous cell carcinoma of the head and neck.
Limited data exist on the burden of comorbidity among patients with squamous cell head and neck cancer (SCCHN) before and during cancer treatment. The precancer prevalence and incidence rates of 8 comorbid conditions were estimated among a population-based cohort of 1499 patients with SCCHN in the Netherlands. Patients with cancer, treatments, and comorbidities were identified in the PHARMO Record Linkage System (RLS) using hospital admissions and/or dispensing codes. Prevalence proportions and incidence rates were also compared against a matched cancer-free population. Cardiovascular (41%) and respiratory diseases (12%) were the most prevalent comorbidities. Incidence rates of most comorbidities were highest the first 6 months after cancer diagnosis and decreased over time. Patients receiving chemotherapy-based treatment had significantly higher incidence rates of anemia and other malignant diseases. High rates of acute and chronic comorbidity were observed; knowledge of comorbidity burden aids in establishing a benefit-risk profile for investigational SCCHN therapies.


Clinical governance: bridging the gap between managerial and clinical approaches to quality of care.
Clinical governance has been introduced as a new approach to quality improvement in the UK national health service. This article maps clinical governance against a discussion of the four main approaches to measuring and improving quality of care: quality assessment, quality assurance, clinical audit, and quality improvement (including continuous quality improvement). Quality assessment underpins each approach. Whereas clinical audit has, in general, been professionally led, managers have driven quality improvement initiatives. Quality assurance approaches have been perceived to be externally driven by managers or to involve professional inspection. It is discussed how clinical governance seeks to bridge these approaches. Clinical governance allows clinicians in the UK to lead a comprehensive strategy to improve quality within provider organisations, although with an expectation of greatly increased external accountability. Clinical governance aims to bring together managerial, organisational, and clinical approaches to improving quality of care. If successful, it will define a new type of professionalism for the next century. Failure by the professions to seize the opportunity is likely to result in increasingly detailed external control of clinical activity in the UK, as has occurred in some other countries.


Lensless two-photon imaging through a multicore fiber with coherence-gated digital phase conjugation.
We performed near-diffraction limited two-photon fluorescence (TPF) imaging through a lensless, multicore-fiber (MCF) endoscope utilizing digital phase conjugation. The phase conjugation technique is compatible with commercially available MCFs with high core density. We demonstrate focusing of ultrashort pulses through an MCF and show that the method allows for resolution that is not limited by the MCF core spacing. We constructed TPF images of fluorescent beads and cells by digital scanning of the phase-conjugated focus on the target object and collection of the emitted fluorescence through the MCF.


Bayesian hierarchical modelling of the geospatial distribution of fasciolosis in dairy cattle and the impact on production: Application to the main milk-producing region (Galicia) in Spain.
Fasciolosis caused by Fasciola hepatica is a common parasitic infection among cattle in many countries. Although infected adult cows rarely show overt clinical signs, milk production may be impaired. Thus, significant production losses may occur in dairy herds with a high prevalence of fasciolosis. In this study, Bayesian hierarchical modelling was used to estimate the geospatial distribution of dairy cattle fasciolosis and its impact on milk production. The study was conducted in Galicia, the main milk producing region in Spain and a geographically heterogeneous area. The aims were: 1) to model the geospatial distribution of fasciolosis in dairy herds in the study area, 2) to identify clusters of herds with a high prevalence of fasciolosis, and 3) to assess the effect of fasciolosis on milk yield and quality. A large number of dairy cattle farms (n = 4907), of which 1660 provided production records, were surveyed. Fasciola infection status was determined by applying the MM3-SERO ELISA test to bulk tank milk samples. A high probability of infection was predicted in several zones, particularly in the centre, northeast and southeast of Galicia. Conversely, the predicted probability was very low in some parts of the northwest of the region. Infections with high within-herd prevalence (> 25% lactating cows infected) predominated. High within-herd prevalence was associated with loss of milk production (-1.387 kg/cow/ day, on average). No association between Fasciola infection and either milk fat or protein content was observed. This study has generated the first maps of the spatial distribution of the probability of Fasciola infection in dairy cattle herds in Galicia. The maps presented here can be used for reference purposes, enabling the design of better targeted fasciolosis control programmes in the region. Use of Bayesian hierarchical statistical analysis enabled us to ascertain the uncertainty of the predictions and to account for the spatial autocorrelation in the data. It also enabled us to generate maps showing the residual spatial variation in milk production, a topic that may deserve more detailed study.


Cloning and functional analysis of the promoters that upregulate carotenogenic gene expression during flower development in Gentiana lutea.
Over the last two decades, many carotenogenic genes have been cloned and used to generate metabolically engineered plants producing higher levels of carotenoids. However, comparatively little is known about the regulation of endogenous carotenogenic genes in higher plants, and this restricts our ability to predict how engineered plants will perform in terms of carotenoid content and composition. During petal development in the Great Yellow Gentian (Gentiana lutea), carotenoid accumulation, the formation of chromoplasts and the upregulation of several carotenogenic genes are temporally coordinated. We investigated the regulatory mechanisms responsible for this coordinated expression by isolating five G. lutea carotenogenic gene (GlPDS, GlZDS, GlLYCB, GlBCH and GlLYCE) promoters by inverse polymerase chain reaction (PCR). Each promoter was sufficient for developmentally regulated expression of the gusA reporter gene following transient expression in tomato (Solanum lycopersicum cv. Micro-Tom). Interestingly, the GlLYCB and GlBCH promoters drove high levels of gusA expression in chromoplast-containing mature green fruits, but low levels in chloroplast-containing immature green fruits, indicating a strict correlation between promoter activity, tomato fruit development and chromoplast differentiation. As well as core promoter elements such as TATA and CAAT boxes, all five promoters together with previously characterized GlZEP promoter contained three common cis-regulatory motifs involved in the response to methyl jasmonate (CGTCA) and ethylene (ATCTA), and required for endosperm expression (Skn-1_motif, GTCAT). These shared common cis-acting elements may represent binding sites for transcription factors responsible for co-regulation. Our data provide insight into the regulatory basis of the coordinated upregulation of carotenogenic gene expression during flower development in G. lutea.


Antibodies for therapeutic uses and the evolution of biotechniques.
Protein therapeutics are playing an expanding role in modern medicinal chemistry. Among them, native or engineered molecules exploiting the binding and catalytic potential of the immune repertoire form an extremely exciting and emerging business area. They represent by far the single largest category of biopharmaceutical substances under investigation. The fast increase of this pharmaceutical category paralleled the scientific and technical progress from murine to chimeric, humanized and, finally, human engineered antibodies. Indeed, the development of the phage display technology, allowing libraries of shuffled murine or human antibody binding domains to be screened for affinity against a selected target antigen or activity against a specific reaction substrate, open new perspectives, disclosing the opportunity to circumvent restrictions inherent to the in vivo immunisation. Transgenic technology represents another powerful method for generating fully human monoclonal antibodies against a wide variety of drug targets, while recombinant technology continues to evolve, improving the pharmacodynamic and pharmacokinetic properties of antibody therapeutics, with the production of different antibody constructs or formats, such as bispecific antibodies, diabodies and others, and different functional activities, such as catalysis, cellular internalisation and antigen-mimicking. The aim of the present review is to overview native or recombinant antibodies while discussing the underlying antibody technology, with the aim to favour understanding of the antibody therapeutics that are in use or will enter market in the near future.


Hemolytic Uremic syndrome associated with pregnancy: Outcome from acute Kidney Injury.
To report here, case series of women developing acute kidney injury (AKI) in association with hemolytic uremic syndrome (HUS) during pregnancy or within days postpartum. Subjects for the study reported here comprised of a cohort of 49 women referred from OBGYN and diagnosed having AKI and HUS. AKI was defined according to RIFLE criteria and HUS on basis of hematological, biochemical and histological features. All patients had normal size kidneys on ultrasonography and no previous co- morbidity. From January 2000 - January 2020, 49 such women were admitted/ referred to this facility. The mean age of these patients was 29.02±5.258 years. Two had HUS during pregnancy while rest during postpartum. Majority of women had more than one insults these include hemorrhages, intrauterine deaths, operative measure (lower segment caesarean section). Renal replacement was required in all women. Complete renal recovery was observed in 14 patients, while one died during acute phase of illness. CKD-V developed in 17 patients, 16 patients lost long term follow up, but were dialysis free till last follow up and one left against medical advice during acute phase of illness. Treatment with plasmapheresis revealed significantly better renal recovery (p value 0.03) in this group of patients. AKI with background of Hemolytic Uremic Syndrome (HUS) may remain irreversible in many of these young women. Plasmapheresis should be offered to patients with established diagnosis of HUS.


Emerging multifunctional roles of Claudin tight junction proteins in bone.
The imbalance between bone formation and resorption during bone remodeling has been documented to be a major factor in the pathogenesis of osteoporosis. Recent evidence suggests a significant role for the tight junction proteins, Claudins (Cldns), in the regulation of bone remodeling processes. In terms of function, whereas Cldns act "canonically" as key determinants of paracellular permeability, there is considerable recent evidence to suggest that Cldns also participate in cell signaling, ie, a "noncanonical function". To this end, Cldns have been shown to regulate cell proliferation, differentiation, and gene expression in a variety of cell types. The present review will discuss Cldns' structure, their expression profile, regulation of expression, and their canonical and non- canonical functions in general with special emphasis on bone cells. In order to shed light on the noncanonical functions of Cldns in bone, we will highlight the role of Cldn-18 in regulating bone resorption and osteoclast differentiation. Collectively, we hope to provide a framework for guiding future research on understanding how Cldns modulate osteoblast and osteoclast function and overall bone homeostasis. Such studies should provide valuable insights into the pathogenesis of osteoporosis, and may highlight Cldns as novel targets for the diagnosis and therapeutic management of osteoporosis.


Global Diversity and Geographic Distributions of Padina Species (Dictyotales, Phaeophyceae): New Insights Based on Molecular and Morphological Analyses.
The taxonomic status and species diversity of the brown algal genus Padina (Dictyotales, Phaeophyceae) was assessed based on DNA sequences and the morpho-anatomy of specimens collected worldwide, especially from tropical and subtropical western Pacific regions. Phylogenetic analyses using chloroplast rbcL and mitochondrial cox3 gene sequences demonstrated four distinct clades for newly collected samples with high bootstrap support. Each species clade possesses a suite of morphological features that are not shared by any known species of Padina. These are P. imbricata sp. nov., Padina lutea sp. nov., P. moffittianoides sp. nov., and P. nitida sp. nov. The occurrence of these and other species of Padina clearly points to an elevated diversity of the genus in tropical/subtropical waters of the western Pacific. Phylogenetic analyses provided new insights into biogeographic characteristics of the genus, with many species in the Pacific Ocean showing shared/overlapping distributions, whereas species from the Mediterranean/Atlantic and/or the Indian Ocean tend to be confined to particular regions. Consideration has also been given to the evolutionary time frame of the genus Padina based on molecular time trees: a time tree of the concatenated data set (rbcL + cox3) revealed the estimated divergence time in the mid-Cretaceous, whereas those of cox3 and rbcL showed older estimates pointing to the periods of mid-Jurassic and Early Cretaceous, respectively.


Effective methods for increasing coumestrol in soybean sprouts.
Coumestrol (CM), a biologically active compound found in Leguminosae plants, provides various human health benefits. To identify easy and effective methods to increase CM content in vegetables, we developed a quantitative analysis method using high-performance liquid chromatography (HPLC). Using this method, we found that soybean sprouts (1.76 ± 0.13 μg/g) have high CM contents among nine vegetables and evaluated the difference in CM contents between two organs of the sprouts: cotyledons and hypocotyls. Next, soybean sprouts were cultivated under different light, temperature, and water conditions and their CM contents were evaluated. CM content was higher in hypocotyls (4.11 ± 0.04 μg/g) than in cotyledons. Cultivating soybean sprouts at 24°C enhanced CM content regardless of light conditions, the growth of fungi and bacteria, and sprout color. Thus, we identified methods of soybean sprout cultivation to increase CM content, which may provide health benefits and enhance value.


Effect of intracisternal thyrotropin-releasing hormone on hepatic blood flow in rats.
Central neuropeptides play a role in many physiological regulatory processes through the autonomic nervous system. Thyrotropin-releasing hormone (TRH) is distributed in the central nervous system and acts as a neurotransmitter to regulate gastric functions through vagal-muscarinic pathways. The central effect of the TRH analog on hepatic blood flow was investigated in urethan-anesthetized rats. Hepatic blood flow was determined by the hydrogen gas clearance technique. Intracisternal injection of the stable TRH analog RX-77368 (5-100 ng) dose dependently increased hepatic blood flow with peak response at 15 min after the peptide was administered (net change from basal for vehicle and 5, 10, 100, and 500 ng RX-77368 was 2.0 +/- 0.2, 8.9 +/- 0.8, 19.4 +/- 2.6, 32.6 +/- 3.3, and 28.5 +/- 6.8 ml.min-1.100 g-1, respectively), and this stimulatory effect returned to baseline at 90 min. The stimulation of hepatic blood flow by the intracisternally administered TRH analog was abolished by atropine methyl nitrate (0.15 mg/kg ip), indomethacin (5 mg/kg ip), NG-nitro-L-arginine methyl ester (10 mg/kg iv), and hepatic branch vagotomy but not by cervical spinal cord transection (C6 level). Intravenous injection of RX-77368 did not have any effect on hepatic blood flow. These results indicate that TRH acts in the central nervous system to stimulate hepatic blood flow through vagal-muscarinic and indomethacin- and nitric oxide-dependent pathways.


Representation and classification of 3-D objects.
This paper addresses the problem of generic object classification from three-dimensional depth or meshed data. First, surface patches are segmented on the basis of differential geometry and quadratic surface fitting. These are represented by a modified Gaussian image that includes the well-known shape index. Learning is an interactive process in which a human teacher indicates corresponding patches, but the formation of generic classes is unaided. Classification of unknown objects is based on the measurement of similarities between feature sets of the objects and the generic classes. The process is demonstrated on a group of three-dimensional (3-D) objects built from both CAD and laser-scanned depth data.


EPFR Formation from Phenol adsorption on Al2O3 and TiO2: EPR and EELS studies.
We have examined the formation of environmentally persistent free radicals (EPFRs) from phenol over alumina and titania using both powder and single-crystal samples. Electron paramagnetic resonance (EPR) studies of phenol adsorbed on metal oxide powders indicates radical formation on both titania and alumina, with both oxides forming one faster-decaying species (lifetime on the order of 50-100 hours) and one slower-decayng species (lifetimes on the order of 1000 hours or more). Electron energy loss spectroscopy (EELS) measurements comparing physisorbed phenol on single-crystal TiO2(110) to phenoxyl radicals on the same substrate indicate distinct changes in the π-π* transitions from phenol after radical formation. The identical shifts are observed from EELS studies of phenoxyl radicals on ultrathin alumina grown on NiAl(110), indicating that this shift in the π-π* transition may be taken as a general hallmark of phenoxyl radical formation.


Viscoelasticity and primitive path analysis of entangled polymer liquids: from F-actin to polyethylene.
We combine computer simulations and scaling arguments to develop a unified view of polymer entanglement based on the primitive path analysis of the microscopic topological state. Our results agree with experimentally measured plateau moduli for three different polymer classes over a wide range of reduced polymer densities: (i) semidilute theta solutions of synthetic polymers, (ii) the corresponding dense melts above the glass transition or crystallization temperature, and (iii) solutions of semiflexible (bio)polymers such as F-actin or suspensions of rodlike viruses. Together, these systems cover the entire range from loosely to tightly entangled polymers. In particular, we argue that the primitive path analysis renormalizes a loosely to a tightly entangled system and provide a new explanation of the successful Lin-Noolandi packing conjecture for polymer melts.


Color tuning in binding pocket models of the chlamydomonas-type channelrhodopsins.
We examined the shift of absorption maxima between the chlamydomonas-type channelrhodopsins (ChRs) and bacteriorhodopsin (BR). Starting from the BR X-ray structure, we modeled the color tuning in the binding pockets of the ChRs by mutating up to 28 amino acids in the vicinity of the chromophore. By applying the efficient self-consistent charge density functional tight binding (SCC-DFTB) method in a quantum mechanical/molecular mechanical (QM/MM) framework, including explicit polarization and calculating excitation energies with the semiempirical OM2/MRCI method and the ab initio SORCI method, we have shown that multiple mutations in the binding pocket of BR causes large hypsochromic shifts that are of the same order as the experimentally observed shifts of the absorption maxima between BR and the ChRs. This study further demonstrates that mutations in the proximity of the Schiff base and complex counterion lead to a stronger but more flexible interaction with the retinal, which could serve as a possible explanation for the spectral patterns found in the ChRs.


Chronic sodium deficit in the immature rat: its effect on adaptation to sodium excess.
The impact of chronic low-sodium intake during early development on body sodium homeostasis is not sufficiently known. To explore this effect, we have investigated the influence of chronic sodium deficit during the rapid growth period of rats (first phase, age 3-7 wk) and the short-term effect of sodium repletion (second phase, age 8-9 wk) on parameters such as growth rate, urinary aldosterone excretion, 22Na volume of distribution (space), and various renal functions. Three groups were studied: group I (control) and groups II and III. During the first phase the respective sodium intake values for these groups were 8.9, 3.1, and 1.5 meq.kg body wt-1.day-1. During the second phase, all groups had sodium intake of 8.7-8.8 meq.kg body wt-1.day-1. At the end of the first phase, group II showed weight gain and 22Na space values similar to those of group I. Group III demonstrated severe growth retardation and reduced 22Na space. During the second phase, both groups II and III demonstrated expansion of the 22Na space and persistently elevated urinary "acid-labile" aldosterone excretions. Despite the 2 wk of sodium repletion, group III failed to catch up with the body weight of groups I and II. It is concluded that chronic sodium deficit during early development transition is made to a higher sodium intake.


Spin blockade in the conduction of colloidal CdSe nanocrystal films.
The conduction of thin films of n-type CdSe colloidal quantum dots is studied at low temperature and under magnetic field. At medium and high magnetic fields (10 T), the films exhibit positive magnetoresistance consistent with the variable range hopping model. At low magnetic field(<0.3 T) but in the strong electric field regime, there is a narrower magnetoresistance of order 10%-15%. The magnetoresistance shows a strong bias dependence, small and positive at low bias, increasing but still positive at higher bias, and turning negative at the highest bias. A similar behavior has been reported recently for thin film organics. Weak localization effects are ruled out. The explanation for the observations is based on spin blockade relaxed by the hyperfine interaction. The weak magnetoresistance at low bias is attributed to the diffusing paths taken by the hopping electrons. At higher bias, the more directed motion of electrons leads to increasingly positive magnetoresistance due to the more effective spin blockade. At the highest bias, the magnetoresistance becomes negative, which is attributed to the increased exchange interaction associated with the shorter tunneling distance.


Modeling cognitive loads for evolving shared mental models in human-agent collaboration.
Recent research on human-centered teamwork highly demands the design of cognitive agents that can model and exploit human partners' cognitive load to enhance team performance. In this paper, we focus on teams composed of human-agent pairs and develop a system called Shared Mental Models for all--SMMall. SMMall implements a hidden Markov model (HMM)-based cognitive load model for an agent to predict its human partner's instantaneous cognitive load status. It also implements a user interface (UI) concept called shared belief map, which offers a synergic representation of team members' information space and allows them to share beliefs. An experiment was conducted to evaluate the HMM-based load models. The results indicate that the HMM-based load models are effective in helping team members develop a shared mental model (SMM), and the benefit of load-based information sharing becomes more significant as communication capacity increases. It also suggests that multiparty communication plays an important role in forming/evolving team SMMs, and when a group of agents can be partitioned into subteams, splitting messages by their load status can be more effective for developing subteam SMMs.


Targeting cancer stem cells through L1CAM suppresses glioma growth.
Malignant gliomas are lethal cancers that display striking cellular heterogeneity. A highly tumorigenic glioma tumor subpopulation, termed cancer stem cells or tumor-initiating cells, promotes therapeutic resistance and tumor angiogenesis. Therefore, targeting cancer stem cells may improve patient survival. We interrogated the role of a neuronal cell adhesion molecule, L1CAM, in glioma stem cells as L1CAM regulates brain development and is expressed in gliomas. L1CAM(+) and CD133(+) cells cosegregated in gliomas, and levels of L1CAM were higher in CD133(+) glioma cells than normal neural progenitors. Targeting L1CAM using lentiviral-mediated short hairpin RNA (shRNA) interference in CD133(+) glioma cells potently disrupted neurosphere formation, induced apoptosis, and inhibited growth specifically in glioma stem cells. We identified a novel mechanism for L1CAM regulation of cell survival as L1CAM knockdown decreased expression of the basic helix-loop-helix transcription factor Olig2 and up-regulated the p21(WAF1/CIP1) tumor suppressor in CD133(+) glioma cells. To determine if targeting L1CAM was sufficient to reduce glioma stem cell tumor growth in vivo, we targeted L1CAM in glioma cells before injection into immunocompromised mice or directly in established tumors. In each glioma xenograft model, shRNA targeting of L1CAM expression in vivo suppressed tumor growth and increased the survival of tumor-bearing animals. Together, these data show that L1CAM is required for maintaining the growth and survival of CD133(+) glioma cells both in vitro and in vivo, and L1CAM may represent a cancer stem cell-specific therapeutic target for improving the treatment of malignant gliomas and other brain tumors.


A modified enzyme-linked immunosorbent assay for the detection of avian pneumovirus antibodies.
Avian pneumovirus (APV) infection of turkeys in Minnesota was first confirmed in March 1997. Serum samples (n = 5,194) from 539 submissions to Minnesota Veterinary Diagnostic Laboratory were tested by a modified enzyme-linked immunosorbent assay (ELISA). Of these, 2,528 (48.7%) samples from 269 submissions were positive and 2,666 (51.3%) samples from 270 submissions were negative for APV antibodies. Most positive samples were from Kandiyohi, Stearns, Morrison, and Meeker counties in Minnesota. In addition, 10 samples from South Dakota were positive. The sensitivity and specificity of the ELISA test with anti-chicken and anti-turkey conjugates were compared by testing field and experimental sera. The ELISA test with anti-turkey conjugate was more sensitive than that with anti-chicken conjugate. The ELISA tests with antigens prepared with APV strains isolated from Colorado and Minnesota were also compared. No difference was detectable. Currently, the Minnesota Veterinary Diagnostic Laboratory uses an antigen prepared from the Colorado isolate of APV and a goat anti-turkey conjugate in the ELISA test.


The Effects of Activation or Inhibition of the Subthalamic Nucleus on the Metabolic and Electrophysiological Activities Within the Pallidal Complex and Substantia Nigra in the Rat.
The changes in local cerebral glucose utilization (LCGU) and neuronal unit activities in the subthalamic nucleus and its major target structures (the pars reticulata of the substantia nigra, the globus pallidus and the entopeduncular nucleus) following microinjection of a GABAergic antagonist (bicuculline methiodide, 0.08 nmol) or agonist (muscimol, 0.2 nmol) into the subthalamic nucleus were determined. The metabolic effect was assessed by measuring LCGU by quantitative [14C]-2-deoxyglucose autoradiography in ketamine-anaesthetized rats. Bicuculline methiodide induced increased LCGU in the ipsilateral globus pallidus, the entopeduncular nucleus and the substantia nigra pars reticulata. In contrast, muscimol decreased LCGU in these structures. The neuronal activities in the subthalamic nucleus and related structures increased following injection of bicuculline and decreased after injection of muscimol. The changes in LCGU within the structures directly related to the subthalamic nucleus were correlated with the changes in the unit activity either in the subthalamic nucleus and/or its projection structures. However, the amplitude of the relative changes in neuronal unit activity were greater than the changes in LCGU. Nevertheless, the results emphasize the functional role of the subthalamic nucleus as an activating structure within the basal ganglia.


The relationship between coping styles in response to unfair treatment and understanding of diabetes self-care.
This study examined the relationship between coping style and understanding of diabetes self-care among African American and white elders in a southern Medicare-managed care plan. Participants were identified through a diabetes-related pharmacy claim or ICD-9 code and completed a computer-assisted telephone survey in 2006-2007. Understanding of diabetes self-care was assessed using the Diabetes Care Profile Understanding (DCP-U) scale. Coping styles were classified as active (talk about it/take action) or passive (keep it to yourself). Linear regression was used to estimate the associations between coping style with the DCP-U, adjusting for age, sex, education, and comorbidities. Based on the conceptual model, 4 separate categories were established for African American and white participants who displayed active and passive coping styles. Of 1420 participants, the mean age was 73 years, 46% were African American, and 63% were female. Most respondents (77%) exhibited active coping in response to unfair treatment. For African American participants in the study, active coping was associated with higher adjusted mean DCP-U scores when compared to participants with a passive coping style. No difference in DCP-U score was noted among white participants on the basis of coping style. Active coping was more strongly associated with understanding of diabetes self-care among older African Americans than whites. Future research on coping styles may give new insights into reducing diabetes disparities among racial/ethnic minorities.


Borderline personality disorder symptoms and criminal justice system involvement: The roles of emotion-driven difficulties controlling impulsive behaviors and physical Aggression.
Borderline personality disorder (BPD) is associated with elevated risk for a variety of risky behaviors, including criminal behaviors. Yet, limited research has examined the relation of BPD to criminal justice (CJ) involvement, or the mechanisms underlying this relation. This study examined the role of two mechanisms, emotion-driven difficulties controlling impulsive behaviors and physical aggression, in the relation between BPD symptom severity and CJ involvement among 118 patients in residential substance abuse treatment (76% male; 62% African-American). Participants completed measures of BPD symptom severity, CJ contact, diversity of CJ charges, emotion-driven impulse control difficulties, physical aggression, and covariates (substance use severity and antisocial personality disorder symptoms). BPD symptom severity was associated with CJ contact through emotion-driven difficulties controlling impulsive behaviors, and with diversity of CJ charges through emotion-driven difficulties controlling impulsive behaviors and physical aggression; however, the indirect relations to diversity of CJ charges became non-significant when covariates were included. Results highlight the important role of emotion-driven difficulties controlling impulsive behaviors in criminal behaviors among individuals with BPD symptoms, as well as the potential clinical utility of targeting this mechanism to prevent CJ involvement and/or recidivism.


An anesthetic experience in a patient with Seckel syndrome: A case report.
Seckel syndrome is an autosomal recessive, primordial dwarfism. The clinical symptoms and signs include severe intrauterine and postnatal growth retardation, nanocephaly, proportional dwarfism, bird-like faces, beak-like triangular nose, and mental retardation. We report a successful anesthetic management including endotracheal intubation with the GlideScope(R) video laryngoscope in an 18-year old man with Seckel syndrome for curettage of chronic osteomyelitis of pelvic bone.


Hispanic women's breast and cervical cancer knowledge, attitudes, and screening behaviors.
This study examined breast and cervical cancer knowledge, attitudes, and screening behaviors among different Hispanic populations in the United States. Data were collected from a random digit dial telephone survey of 8903 Hispanic adults from eight U.S. sites. Across sites, the average response rate was 83%. Data were collected as part of the baseline assessment in a national Hispanic cancer control and prevention intervention study. Analysis was restricted to 2239 Hispanic women age 40 and older who were self-identified as either Central American (n = 174), Cuban (n = 279), Mexican American (n = 1550), or Puerto Rican (n = 236). A bilingual survey instrument was used to solicit information on age, education, income, health insurance coverage, language use, U.S.-born status, knowledge of screening guidelines, attitudes toward cancer, and screening participation. Differences in knowledge and attitudes across Hispanic groups were assessed by either chi-square tests or analysis of variance. Logistic regression models assessed the influence of knowledge and attitudes on screening participation. The level of knowledge of guidelines ranged from 58.3% (Mexican Americans) to 71.8% (Cubans) for mammography, and from 41.1% (Puerto Ricans) to 55.6% (Cubans) for Pap smear among the different Hispanic populations. Attitudes also varied, with Mexican Americans and Puerto Ricans having more negative or fatalistic views of cancer than Cuban or Central Americans. Knowledge was significantly related to age, education, income, language preference, and recent screening history. Overall, attitudes were not predictive of mammography and Pap smear behavior. Factors related to mammography and Pap smear screening vary among the different Hispanic populations. Limitations include the cross-sectional nature of the study, self-reported measures of screening, and the limited assessment of attitudes. The data and diversity of Hispanic groups reinforce the position that ethno-regional characteristics should be clarified and addressed in cancer screening promotion efforts. The practical relationships among knowledge, attitudes, and cancer screening are not altogether clear and require further research.


Regulation of neural responses to emotion perception by ketamine in individuals with treatment-resistant major depressive disorder.
The glutamate N-methyl-D-aspartate receptor antagonist ketamine has demonstrated antidepressant effects in individuals with treatment-resistant major depressive disorder (TRD) within 24 h of a single dose. The current study utilized functional magnetic resonance imaging (fMRI) and two separate emotion perception tasks to examine the neural effects of ketamine in patients with TRD. One task used happy and neutral facial expressions; the other used sad and neutral facial expressions. Twenty patients with TRD free of concomitant antidepressant medication underwent fMRI at baseline and 24 h following administration of a single intravenous dose of ketamine (0.5 mg kg(-1)). Adequate data were available for 18 patients for each task. Twenty age- and sex-matched healthy volunteers were scanned at one time point for baseline comparison. Whole-brain, voxel-wise analyses were conducted controlling for a family-wise error rate (FWE) of P<0.05. Compared with healthy volunteers, TRD patients showed reduced neural responses to positive faces within the right caudate. Following ketamine, neural responses to positive faces were selectively increased within a similar region of right caudate. Connectivity analyses showed that greater connectivity of the right caudate during positive emotion perception was associated with improvement in depression severity following ketamine. No main effect of group was observed for the sad faces task. Our results indicate that ketamine specifically enhances neural responses to positive emotion within the right caudate in depressed individuals in a pattern that appears to reverse baseline deficits and that connectivity of this region may be important for the antidepressant effects of ketamine.


A Randomized, Nonblind, Naturalistic Comparison of Efficacy and Cognitive Outcomes With Right Unilateral, Bifrontal, and Bitemporal Electroconvulsive Therapy in Schizophrenia.
There is little literature on the relative efficacy and cognitive safety of right unilateral (RUL), bifrontal (BF), and bitemporal (BT) electroconvulsive therapy (ECT) in schizophrenia. We present a randomized, nonblind, naturalist comparison of a fixed course of 8 moderately high-dose RUL (n = 24), threshold BF (n = 27), and threshold BT (n = 31) ECT in patients with schizophrenia. Assessments included the Positive and Negative Syndrome Scale (PANSS), the Wechsler Memory Scale-Revised, and an autobiographical memory interview. A completer analysis was planned and conducted to capture the cognitive outcomes. The sample as a whole improved significantly on all efficacy outcomes and deteriorated significantly on all cognitive outcomes. The primary efficacy outcome, improvement in PANSS total scores, did not differ significantly across groups. The PANSS positive score (but no other subscale score) improved significantly less with RUL relative to BF and BT ECT. For autobiographical memory and for almost all Wechsler Memory Scale subtests, including memory quotient (the primary adverse effect outcome), BT ECT was associated with greater impairment than RUL or BF ECT. Importantly, all statistically significant differences between treatments were clinically small in magnitude. In patients with schizophrenia who receive a fixed course of 8 ECTs, threshold BT ECT is associated with greater cognitive impairment across a range of measures, and moderately high-dose RUL ECT is associated with poorer efficacy against positive symptoms. Threshold BF ECT exhibits the best efficacy-cum-neurocognitive safety profile. All differences between groups, however, are small and perhaps clinically insignificant.


Description of two waterborne disease outbreaks in France: a comparative study with data from cohort studies and from health administrative databases.
Waterborne disease outbreaks (WBDO) of acute gastrointestinal illness (AGI) are a public health concern in France. Their occurrence is probably underestimated due to the lack of a specific surveillance system. The French health insurance database provides an interesting opportunity to improve the detection of these events. A specific algorithm to identify AGI cases from drug payment reimbursement data in the health insurance database has been previously developed. The purpose of our comparative study was to retrospectively assess the ability of the health insurance data to describe WBDO. Data from the health insurance database was compared with the data from cohort studies conducted in two WBDO in 2010 and 2012. The temporal distribution of cases, the day of the peak and the duration of the epidemic, as measured using the health insurance data, were similar to the data from one of the two cohort studies. However, health insurance data accounted for 54 cases compared to the estimated 252 cases accounted for in the cohort study. The accuracy of using health insurance data to describe WBDO depends on the medical consultation rate in the impacted population. As this is never the case, data analysis underestimates the total number of AGI cases. However this data source can be considered for the development of a detection system of a WBDO in France, given its ability to describe an epidemic signal.


Microbial interactions within a cheese microbial community.
The interactions that occur during the ripening of smear cheeses are not well understood. Yeast-yeast interactions and yeast-bacterium interactions were investigated within a microbial community composed of three yeasts and six bacteria found in cheese. The growth dynamics of this community was precisely described during the ripening of a model cheese, and the Lotka-Volterra model was used to evaluate species interactions. Subsequently, the effects on ecosystem functioning of yeast omissions in the microbial community were evaluated. It was found both in the Lotka-Volterra model and in the omission study that negative interactions occurred between yeasts. Yarrowia lipolytica inhibited mycelial expansion of Geotrichum candidum, whereas Y. lipolytica and G. candidum inhibited Debaryomyces hansenii cell viability during the stationary phase. However, the mechanisms involved in these interactions remain unclear. It was also shown that yeast-bacterium interactions played a significant role in the establishment of this multispecies ecosystem on the cheese surface. Yeasts were key species in bacterial development, but their influences on the bacteria differed. It appeared that the growth of Arthrobacter arilaitensis or Hafnia alvei relied less on a specific yeast function because these species dominated the bacterial flora, regardless of which yeasts were present in the ecosystem. For other bacteria, such as Leucobacter sp. or Brevibacterium aurantiacum, growth relied on a specific yeast, i.e., G. candidum. Furthermore, B. aurantiacum, Corynebacterium casei, and Staphylococcus xylosus showed reduced colonization capacities in comparison with the other bacteria in this model cheese. Bacterium-bacterium interactions could not be clearly identified.


Tumour necrosis factor alpha alters the expression of connexin43, connexin40, and connexin37 in human umbilical vein endothelial cells.
Tumour necrosis factor alpha (TNF-alpha) plays an important role in orchestrating inflammatory responses with the vascular endothelium as main target cell type, and was found to promote migration of endothelial cells, as occurs in wound healing processes. Substantial evidence exists that endothelial cell migration in wound healing is related to changes in cell coupling by means of gap junctions. Gap junctions are agglomerates of cell-to-cell channels that allow direct electrical and metabolic communication between cells. The authors have investigated whether TNF-alpha alters the expression of gap junction proteins (connexins, Cx) between human umbilical vein endothelial cells (HUVEC), thereby changing the extent of intercellular communication, as measured by dye coupling. Under control conditions, Cx43, Cx40, and Cx37 protein and mRNA were present in HUVEC. After exposure to 0.5 nM TNF-alpha for 48 h, however, the authors were no longer able to detect Cx37 and Cx40 protein, whereas Cx43 levels seemed unaltered but showed more perinuclear staining. After 24 and 48 h exposure to TNF-alpha, levels of Cx37 and Cx40 mRNA, were reduced, while the level of Cx43 mRNA remained unaltered, suggesting transcriptional regulation. If TNF-alpha was removed from the medium, Cx37 and Cx40 expression was restored within 24 h. The modulation of connexin expression by TNF-alpha resulted in a decrease in dye coupling of 40%.


Discovery of Clinical Candidate NT-0796, a Brain-Penetrant and Highly Potent NLRP3 Inflammasome Inhibitor for Neuroinflammatory Disorders.
The NLRP3 inflammasome is a component of the innate immune system involved in the production of proinflammatory cytokines. Neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis, have been shown to have a component driven by NLRP3 inflammasome activation. Diseases such as these with large unmet medical needs have resulted in an interest in inhibiting the NLRP3 inflammasome as a potential pharmacological treatment, but to date, no marketed drugs specifically targeting NLRP3 have been approved. Furthermore, the requirement for CNS-penetrant molecules adds additional complexity to the search for NLRP3 inflammasome inhibitors suitable for clinical investigation of neuroinflammatory disorders. We designed a series of ester-substituted carbamate compounds as selective NLRP3 inflammasome inhibitors, leading to NT-0796, an isopropyl ester that undergoes intracellular conversion to NDT-19795, the carboxylic acid active species. NT-0796 was shown to be a potent and selective NLRP3 inflammasome inhibitor with demonstrated in vivo brain penetration.


Nutritional intake in children with renal insufficiency: a report of the growth failure in children with renal diseases study.
This study was designed to assess sequentially the nutrient intake in children with chronic renal insufficiency and its relationship to body size, the level of renal failure, and growth velocity. The nutrient intake from 401 4-day food records obtained from 120 children with renal insufficiency over a 6-month observation period was analyzed. The height and weight were measured at the beginning and end of the observation period. The glomerular filtration rate was estimated from the height and serum creatinine. The mean caloric intake in these children was 80 +/- 23% (mean +/- SD) of the Recommended Dietary Allowance (RDA) for age. Fifty-six percent of the food records obtained from these children revealed a caloric intake that was less than 80% of the RDA. Caloric intake expressed as the %RDA for age decreased with increasing age. However, the mean caloric intake when factored by body weight was in the normal range. There was no correlation between caloric intake and height velocity. The mean protein intake in these children was 153 +/- 53% of the RDA. Further, 45% of the food records indicated a protein intake greater than 150% of the RDA. There was no relationship between the degree of renal insufficiency and caloric or protein intake. Calcium, vitamin, and zinc intakes were also low. Children with chronic renal failure consume less calories than their age matched peers, but the majority of these children appear to ingest adequate amounts for their body mass. This reduction in caloric intake occurs early in renal insufficiency. They also ingest inadequate amounts of calcium, zinc, vitamin B6, and folate.


Prosthetic valve endocarditis from Mycobacterium chimaera infection causing granulomatous interstitial nephritis.
Mycobacterium chimaera is a rare infection associated with cardiopulmonary bypass. We describe a case of granulomatous interstitial nephritis caused by M. chimaera in a patient with prosthetic aortic valve endocarditis. A 63-year-old female with a mechanical aortic valve replacement developed fatigue, 20 lbs. weight loss, anemia, and an elevated creatinine. Fat pad aspirate at an outside hospital was suspicious for amyloidosis which prompted hematology referral at our institution. Bone marrow biopsy revealed a single granuloma, negative for amyloid or acid fast bacillus (AFB). She was admitted to our hospital for worsening kidney function refractory to intravenous fluid challenge. Transesophageal echocardiogram showed aortic root abscess and valve vegetation with negative blood cultures at seven days. Renal biopsy showed granulomatous interstitial nephritis and negative AFB stain. Prednisone 40 mg was started and renal function partially improved. Blood cultures obtained before biopsy subsequently grew M. chimaera. Three-drug antimicrobial therapy was initiated and prednisone discontinued. One month later, creatinine improved and follow up echocardiogram showed no lesion. Our case highlights this rare infection inducing granulomatous interstitial nephritis despite lack of positive AFB or gram stains on renal biopsy.


Pattern of ubiquilin pathology in ALS and FTLD indicates presence of C9ORF72 hexanucleotide expansion.
C9ORF72-hexanucleotide repeat expansions and ubiquilin-2 (UBQLN2) mutations are recently identified genetic markers in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). We investigate the relationship between C9ORF72 expansions and the clinical phenotype and neuropathology of ALS and FTLD. Genetic analysis and immunohistochemistry (IHC) were performed on autopsy-confirmed ALS (N = 75), FTLD-TDP (N = 30), AD (N = 14), and controls (N = 11). IHC for neurodegenerative disease pathology consisted of C9ORF72, UBQLN, p62, and TDP-43. A C9ORF72 expansion was identified in 19.4 % of ALS and 31 % of FTLD-TDP cases. ALS cases with C9ORF72 expansions frequently showed a bulbar onset of disease (57 %) and more rapid disease progression to death compared to non-expansion cases. Staining with C9ORF72 antibodies did not yield specific pathology. UBQLN pathology showed a highly distinct pattern in ALS and FTLD-TDP cases with the C9ORF72 expansion, with UBQLN-positive cytoplasmic inclusions in the cerebellar granular layer and extensive UBQLN-positive aggregates and dystrophic neurites in the hippocampal molecular layer and CA regions. These UBQLN pathologies were sufficiently unique to allow correct prediction of cases that were later confirmed to have C9ORF72 expansions by genetic analysis. UBQLN pathology partially co-localized with p62, and to a minor extent with TDP-43 positive dystrophic neurites and spinal cord skein-like inclusions. Our data indicate a pathophysiological link between C9ORF72 expansions and UBQLN proteins in ALS and FTLD-TDP that is associated with a highly characteristic pattern of UBQLN pathology. Our study indicates that this pathology is associated with alterations in clinical phenotype, and suggests that the presence of C9ORF72 repeat expansions may indicate a worse prognosis in ALS.


Myelopathy following intrathecal chemotherapy in adults: a single institution experience.
Methotrexate and cytarabine arabinoside are frequently administered intrathecally in the prophylaxis and treatment of patients with hematological malignancies. Myelopathy as a complication of intrathecal (IT) chemotherapy is rare in adults, with most of the cases described in the literature occurring in the pediatric population. Between January 2010 and March 2014, 587 newly diagnosed B cell acute lymphoblastic leukemia and 24 chronic myeloid leukemia lymphoid blast phase patients were seen at The University of Texas MD Anderson Cancer Center. This case series discusses seven adult cases deemed to have IT chemotherapy-induced myelopathy between 2010 and 2014 at MD Anderson Cancer Center. Five out of the seven patients had T2 abnormalities involving the dorsal columns of the spinal cord. An elevated myelin basic protein level was noted in the two patients in whom it was checked. The wide range of dosage and timing with respect to IT chemotherapy administration suggests an idiosyncratic reaction or individual threshold to the development of myelopathy. By describing the largest case series of myelopathy in adults, we aim to raise awareness about this rare albeit devastating complication. Based on the seven cases described we would recommend-MRI of the spine with T2-weighted imaging in the sagittal and axial planes in leukemia patients with unexplained myelopathy and consideration to delay IT chemotherapy until after an extensive work-up to rule out CNS leukemia. Though more data are needed on the use of folate metabolites, preliminary results have shown some promise in the treatment of methotrexate-induced myelopathy and may be a potential consideration for future patients suspected to have chemotherapy induced myelopathy.


Evolutionary psychology and health: confronting an evolving paradigm.
In much the same way that developments in genetics have opened up new areas of activity in health services, the 'new genetics' has also stimulated a renewal in approaches that try to explain the nature of health behaviours within the context of human biological development. Evolutionary psychology, as an umbrella term for these views, stresses the importance of the brain as an intermediary between genes and individual behaviour. From such a perspective, social context is less important than an understanding of why certain behaviours are 'chosen' by the evolutionary process and how they are predicated on reproductive success. Health policy is a key area where these ideas are likely to become important given evolutionary psychology's focus on the interplay between physiological and psychological factors in determining health behaviours. Health research provides a fertile environment because it is already seeking the hidden biological pathways connecting social status with specific diseases. The challenge represented by evolutionary psychology needs to be taken seriously because of the way in which such ideas mesh with the individualistic basis of much health promotion and health policy. In particular, it poses a challenge when it purports to explain how inequalities in health are not necessarily the result of the unequal distribution of income in society but are natural phenomena. It is also important to engage with such ideas because they increasingly seem likely to occupy the empty ideological space created by the disappearance of politics in policy and as such may have a greater impact than would otherwise be the case.


Integration and spike initiation in neuronal terminals.
Axoaxonal synapses impinge on the terminals of neurons and are thought to play a crucial role in the regulation of synaptic transmission. In the crayfish brain, the terminals of several identified interneurons exhibit both EPSPs and IPSPs in response to cephalic sensory stimulation. The terminal arbors extend into primary sensory neuropils near the terminals of primary afferent axons of the antennae and statocysts. The EPSPs arise monosynaptically from primary afferent stimulation and can elicit action potentials. Bidirectional conduction is routinely observed. Terminal IPSPs are transmitted via a polysynaptic pathway. Furthermore, two morphological classes of synaptic profiles impinge on the presynaptic terminals. These results indicate that the neuron terminal can function as a second, independent site of synaptic integration.


Drinking water contamination from perfluoroalkyl substances (PFAS): an ecological mortality study in the Veneto Region, Italy.
Perfluoroalkyl substances (PFAS), a heterogeneous group of highly stable man-made chemicals, have been widely used since 1960s and can be detected almost ubiquitously in all environmental matrices. In Italy, on January 2014, drinking water contamination in an area of the Veneto Region was detected mainly due to the drain of fluorinated chemicals by a manufacturing company operating since 1964. The present ecological mortality study was aimed at comparing mortality for some causes of death selected on the basis of previous reported associations, during the period 1980-2013, in municipalities with PFAS contaminated and uncontaminated drinking water on the basis of the levels indicated by the Italian National Health Institute (ISS). Sex-specific number, standardized mortality rates and rate ratios (RR) for PFAS contaminated and uncontaminated areas were computed for each cause of death through the ENEA epidemiological database. In both sexes, statistically significant RRs were detected for all causes mortality, diabetes, cerebrovascular diseases, myocardial infarction and Alzheimer's disease. In females, RRs significantly higher than 1.0 were also observed for kidney and breast cancer, and Parkinson's disease. Increased risk, although not statistically significant, was observed for bladder cancer in both sexes, and for testicular cancer, pancreatic cancer and leukemia in males only. Higher mortality levels for some causes of death, possibly associated with PFAS exposure, were detected in contaminated municipalities in comparison with uncontaminated ones with similar socioeconomic status and smoking habits. These results warrant further individual level analytic studies to delineate casual associations.


Macrolide- and tetracycline-resistance determinants of colonizing group B streptococcus in women in Egypt.
Group B streptococcus (GBS) is a commensal bacterium of the human gastrointestinal and genital tracts. It is a leading cause of neonatal sepsis and meningitis, and has also been recognized as an important pathogen in pregnant women and the elderly. We investigated mechanisms of macrolide and tetracycline resistance in GBS colonizing women in Egypt. A total of 100 isolates were screened using standard antibiotic susceptibility tests. A multiplex PCR assay was used to detect macrolide- and tetracycline-resistance determinants. All isolates were uniformly susceptible to penicillin G, ampicillin, cefotaxime, vancomycin and levofloxacin. The resistance rates to erythromycin, clindamycin, azithromycin, tetracycline and chloramphenicol were 17, 14, 16, 98 and 1 %, respectively. Among the erythromycin-resistant isolates, 82.4 % had constitutive macrolide-lincosamide-streptogramin B (cMLSB) resistance, 5.9 % had inducible MLSB (iMLSB) resistance and 11.8 % had M phenotype resistance. Among the cMLSB phenotypes, 64.3 % of isolates harboured the ermB gene and 35.7 % of isolates harboured none of the investigated macrolide-resistance genes. The single strain expressing the iMLSB phenotype possessed the ermA gene. Of the two strains with the M phenotype, only one possessed the mefA/E gene. Conversely, seven macrolide-sensitive strains (MIC <0.03 µg ml(-1)) were ermB positive and one macrolide-sensitive strain (MIC <0.03 µg ml(-1)) harboured mefA/E. Tetracycline resistance was predominantly due to tetM, which was detected alone (83.7 %) or in association with tetL (12.2 %), tetK (1 %) or tetO (1 %). One strain carried tetM associated with both tetL and tetK, and another strain carried tetO alone. The tetO strains were positive for the mefA/E gene, and the tetL and tetK carrier strains harboured the ermB gene. Susceptible strains harbouring but not expressing an antibiotic-resistance gene should be regarded as potentially resistant. These results emphasize the need to monitor the epidemiology of GBS antibiotic resistance in Egypt.


[An assessment of the mental status of miners exposed to the noise load].
The use of psychological-and-diagnostic techniques ant tests designed to study the mental condition and to evaluate the efficiency of psychological adaptation will ensure an early detection of different disorders in the mental status of miners and a differentiation of the population according to their prevalence, which is of a great prognostication importance. The choice of the most informative indices of the miners' psychological status will make it possible to use them in evaluating the professional adaptability of young experts mastering the mining skills, which would maintain a high standard of health and labor longevity.