Prevalence of target anaerobes associated with chronic periodontitis.
Periodontal diseases are a group of chronic infections that destroy tissues surrounding and supporting the teeth. Data on the anaerobes associated with periodontal infections in Kuwait is lacking. To investigate the target anaerobes associated with chronic periodontitis (CP) in patients admitted to Dental Clinics in Kuwait University Health Sciences Center, Kuwait. Patients with CP (severe and moderate) were recruited into this study during a period of 15 months. Samples were collected directly from inside the gingival pockets and subjected to semi-quantitative PCR assays. A total of 30 patients, stratified into moderate and severe CP and 31 healthy individuals, used as controls, were studied. Nine (30 %) of the 30 patients were in the 50-59-year age group. The detection rate of Aggregatibacter actinomycetemcomitans between the patients (9 : 30 %) versus the controls (5 : 16.1 %) was non-significant (P >0.05). Fusobacterium spp., were detected in all patients versus 29 (93.1 %) controls, (P >0.05). However, four target anaerobes were significantly associated with CP patients; Porphyromonas gingivalis was detected in ten (33.3 %) patients versus two (6.4 %) controls (P <0.0001); Tannerella forsythia 25 (83.3 %) versus 16 (51.6 %) controls (P <0.0001); Parvimonas micra 27 (90 %) versus 16 (51.6 %) controls (P <0.0001) and Treponema denticola, 18 (60 %) versus nine (29 %) controls (P <0.0001), respectively. Prevotella spp. were detected in 27 (90 %) patients and 30 (96.7 %) controls (P>0.5). There was no significant difference in the burden of Prevotella spp. between patients and controls determined by semi-quantitative PCR assays. Some (4/7) of the target anaerobes were significantly associated with CP in our study. P. gingivalis was the most strongly associated anaerobe with CP, although not the keystone bacteria, while Prevotella spp. was similar to the healthy controls.


Implantation in interplanetary dust of rare-gas ions from solar flares.
Measurements of excess Ar(36) + Ar(38) ( released mainly at 1200 degrees C) in magnetic concentrates of Pacific sediments and in a dense concentrate of Greenland dust agree within an order of magnitude with expected concentrations implanted by solar-flare ion streams of energy less than 10 Mev per atomic-mass unit. The agreement implies that more than 10 percent of each concentrate may be extraterrestrial, depending on size distribution and flare spectra. Rare-gas measurements on fine-grained dust can provide data on: solar-flare "paleo-ion" fluxes, energy spectra, and isotopic abundances; identification, mineralogy, and chemistry of interplanetary dust; influx rates to Earth and sedimentation rates of oceanic cores; and lunar-surface residence and mixing times.


The role of carotid duplex ultrasound in evaluating plaque morphology: potential use in selecting patients for carotid stenting.
To study the role of duplex ultrasonography in evaluating plaque morphology and its correlation to neurological symptoms and cerebral infarctions on computed tomographic scans. The hospital records of 181 patients (107 males; average age 66 years, range 41 to 89) with > 50% carotid stenosis (29 bilateral lesions) who had undergone duplex ultrasonography, carotid arteriography, and cerebral computed tomography were studied retrospectively. Of 210 duplex examinations, 139 were appropriate for morphological analysis of surface characteristics and echogenicity. Over half of the plaques examined had irregular surfaces (81, 58%) and displayed mixed (i.e., heterogeneous) echogenic patterns (74, 53%). Irregular (68 of 81, 84%) and heterogeneous (65 of 74, 88%) plaques were associated with ipsilateral neurological symptoms (p < 0.0001). Similarly, 44 (54%) of 81 irregular plaques and 42 (57%) of 74 heterogeneous plaques were found in patients with cerebral infarctions in the carotid territory (p < 0.0001). Heterogeneous and/or irregular plaques were more often associated with both neurological symptoms and infarctions than smooth or homogeneous plaques. These findings may have implications in patient selection for endoluminal therapy.


Effects of pre- and postnatal exposure to extremely low-frequency electric fields on mismatch negativity component of the auditory event-related potentials: Relation to oxidative stress.
In our previous study, the developmental effects of extremely low-frequency electric fields (ELF-EF) on visual and somatosensory evoked potentials in adult rats were studied. There is no study so far examining the effects of 50 Hz electric field (EF) on mismatch negativity (MMN) recordings after exposure of rats during development. Therefore, our present study aimed to investigate MMN and oxidative brain damage in rats exposed to EF (12 kV/m, 1 h/day). Rats were divided into four groups, namely control (C), prenatal (Pr), postnatal (Po), and prenatal+postnatal (PP). Pregnant rats of Pr and PP groups were exposed to EF during pregnancy. Following birth, rats of PP and Po groups were exposed to EF for three months. After exposure to EF, MMN was recorded by electrodes positioned stereotaxically to the surface of the dura, and then brain tissues were removed for histological and biochemical analyses. The MMN amplitude was higher to deviant tones than to standard tones. It was decreased in all experimental groups compared with the C group. 4-Hydroxy-2-nonenal (4-HNE) levels were significantly increased in the Po group with respect to the C group, whereas they were significantly decreased in the PP group compared with Pr and Po groups. Protein carbonyl levels were significantly decreased in the PP group compared with C, Pr, and Po groups. EF decreased MMN amplitudes were possibly induced by lipid peroxidation.


The acyl-enzyme mechanism of beta-lactamase action. The evidence for class C Beta-lactamases.
Methanol or ethanol can replace water in the action of certain chromosomal beta-lactamases on benzylpenicillin: the products are alpha-methyl or alpha-ethyl benzylpenicilloate. The beta-lactamases were from a mutant of Pseudomonas aeruginosa 18S that produces the enzyme constitutively [Flett, Curtis & Richmond (1976) J. Bacteriol. 127, 1585-1586; Berks, Redhead & Abraham (1982) J. Gen. Microbiol. 128, 155-159] and from Escherichia coli K12 (the ampC beta-lactamase) [Lindström, Boman & Steele (1970) J. Bacteriol. 101, 218-231]. The variation of the rates of alcoholysis and hydrolysis with concentration of alcohol show that the rate-determining step is breakdown of an intermediate. This intermediate is likely to be the acyl-enzyme. The esters, alpha-methyl or alpha-ethyl benzylpenicilloate, are themselves substrates for the Pseudomonas beta-lactamase, benzylpenicilloic acid being formed. Thus this beta-lactamase can be an esterase. The kinetics for the hydrolysis of cloxacillin by the Pseudomonas beta-lactamase are consistent with the acyl-enzyme, formed by acylation of serine-80, being an intermediate in the overall hydrolysis.


Design of phase III trials with long-term survival outcomes based on short-term binary results.
Pathologic complete response (pCR) is a common primary endpoint for a phase II trial or even accelerated approval of neoadjuvant cancer therapy. If granted, a two-arm confirmatory trial is often required to demonstrate the efficacy with a time-to-event outcome such as overall survival. However, the design of a subsequent phase III trial based on prior information on the pCR effect is not straightforward. Aiming at designing such phase III trials with overall survival as primary endpoint using pCR information from previous trials, we consider a mixture model that incorporates both the survival and the binary endpoints. We propose to base the comparison between arms on the difference of the restricted mean survival times, and show how the effect size and sample size for overall survival rely on the probability of the binary response and the survival distribution by response status, both for each treatment arm. Moreover, we provide the sample size calculation under different scenarios and accompany them with the R package survmixer where all the computations have been implemented. We evaluate our proposal with a simulation study, and illustrate its application through a neoadjuvant breast cancer trial.


Prickle1b mediates interpretation of migratory cues during zebrafish facial branchiomotor neuron migration.
The facial branchiomotor neurons undergo a characteristic tangential migration in the vertebrate hindbrain. Several signaling mechanisms have been implicated in this process, including the non-canonical Wnt/planar cell polarity (PCP) pathway. However, the role of this signaling pathway in controlling the dynamics of these neurons is unclear. Here, we describe the cellular dynamics of the facial neurons as they migrate, focusing on the speed and direction of migration, extension of protrusions, cell shape, and orientation. Furthermore, we show that the PET/LIM domain protein Prickle1b (Pk1b) is required for several aspects of these migratory behaviors, including cell orientation. However, we find that centrosome localization is not significantly affected by disruption of Pk1b function, suggesting that polarization of the neurons is not completely lost. Together, our data suggest that Pk1b function may be required to integrate the multiple migratory cues received by the neurons into polarization instructions for proper posterior movement.


Severe pulmonary hypertension and arterial adventitial changes in newborn calves at 4,300 m.
Some human newborns have a syndrome characterized by irreversible pulmonary hypertension and severe hypoxemia and by medial hypertrophy and adventitial thickening of pulmonary arteries. We considered that newborn calves made severely hypoxic might reproduce features of the human disease. When 2-day-old calves were placed at 4,300 m simulated altitude, pulmonary arterial pressure was increased and could be reversed by 100% O2. However, after 2 wk at 4,300 m, pulmonary arterial pressures were suprasystemic and there was right-to-left shunting probably through the foramen ovale and a patent but restrictive ductus arteriosus. Suprasystemic pulmonary pressure and hypoxemia persisted with 100% O2 breathing. Morphometrical examination of the lung arteries showed a markedly thickened adventitia with cellular proliferation and collagen and elastin deposition. There was increased medial thickness and distal muscularization of the pulmonary arteries associated with decreased luminal diameter. The rapid development of severe pulmonary hypertension and poor responsiveness to O2 was associated with increased arterial wall thickness, particularly involving the adventitia. Thus the pulmonary arterial circulation in these calves, which were placed at high altitude for 2 wk, exhibited features resembling persistent pulmonary hypertension in newborn infants.


Premium ethylcellulose polymer based architectures at work in drug delivery.
Premium ethylcellulose polymers are hydrophobic cellulose ether based biomaterials widely employed as biocompatible templates for the design of novel drug delivery systems. They are classified as United States Food and Drug Administration Generally-Recognized-As-Safe chemical substances and have been extensively utilized within the biomedical and pharmaceutical industries for over half a century. They have so far demonstrated the potential to modulate and improve the physiological performance of bioactives leading to the desired enhanced prophylactic and therapeutic outcomes. This review therefore presents a scholarly survey of inter-disciplinary developments focused on the functionalities of ethylcellulose polymers as biomaterials useful for the design of smart delivery architectures for relevant pharmacotherapeutic biomedical applications. Emphasis was placed on evaluating scientific resources related to recent advancements and future directions associated with its applications as delivery systems for drugs and biologics within the past decade thus complementing other specialized reviews showcasing the theme.


Effect of the Affordable Care Act's young adult insurance expansions on hospital-based mental health care.
Insurance coverage for young adults has increased since 2010, when the Affordable Care Act (ACA) required insurers to permit children to remain on parental policies until age 26 as dependents. This study estimated the association between the dependent coverage provision and changes in young adults' use of hospital-based services for substance use disorders and non-substance use psychiatric disorders. The authors conducted a quasi-experimental comparison of a national sample of non-childbirth-related inpatient admissions to general hospitals (a total of 2,670,463 admissions, 430,583 of which had primary psychiatric diagnoses) and California emergency department visits with psychiatric diagnoses (N=11,139,689), using data spanning 2005 to 2011. Analyses compared young adults who were targeted by the ACA dependent coverage provision (19- to 25-year-olds) and those who were not (26- to 29-year-olds), estimating changes in utilization before and after implementation of the dependent coverage provision. Primary outcome measures included quarterly inpatient admissions for primary diagnoses of any psychiatric disorder per 1,000 population; emergency department visits with any psychiatric diagnosis per 1,000 population; and payer source. Dependent coverage expansion was associated with 0.14 more inpatient admissions for psychiatric diagnoses per 1,000 for 19- to 25-year-olds (targeted by the ACA) than for 26- to 29-year-olds (not targeted by the ACA). The coverage expansion was associated with 0.45 fewer psychiatric emergency department visits per 1,000 in California. The probability that inpatient admissions nationally and emergency department visits in California were uninsured decreased significantly. ACA dependent coverage provisions produced modest increases in general hospital psychiatric inpatient admissions and higher rates of insurance coverage for young adults nationally. Lower rates of emergency department visits were observed in California.


Tyrosine phosphorylation of band 3 protein in Ca2+/A23187-treated human erythrocytes.
Human erythrocytes were induced to release membrane vesicles by treatment with Ca2+ and ionophore A23187. In addition to the biochemical changes already known to accompany loading of human erythrocytes with Ca2+, the present study reveals that tyrosine phosphorylation of the anion exchanger band 3 protein also occurs. The relationship between tyrosine phosphorylation of band 3 and membrane vesiculation was analysed using quinine (a non-specific inhibitor of the Ca(2+)-activated K+ channel, and the only known inhibitor of Ca(2+)-induced vesiculation) and charybdotoxin, a specific inhibitor of the apamin-insensitive K(+)-channel. Both inhibitors suppressed tyrosine phosphorylation of band 3. In the presence of quinine, membrane vesiculation was also suppressed. In contrast, at the concentration of charybdotoxin required to suppress tyrosine phosphorylation of band 3, membrane vesiculation was only mildly inhibited (16-23% inhibition), suggesting that tyrosine phosphorylation of band 3 is not necessary for membrane vesiculation. Phosphorylation of band 3 was in fact observed when erythrocytes were induced to shrink in a Ca(2+)-independent manner, e.g. by treatment with the K+ ionophore valinomycin or with hypertonic solutions. These observations suggest that band 3 tyrosine phosphorylation occurs when cell volume regulation is required.


Depression and obesity: do shared genes explain the relationship?
Studies have found a modest association between depression and obesity, especially in women. Given the substantial genetic contribution to both depression and obesity, we sought to determine whether shared genetic influences are responsible for the association between these two conditions. Data were obtained from 712 monozygotic and 281 dizygotic female twin pairs who are members of the community-based University of Washington Twin Registry. The presence of depression was determined by self-report of doctor-diagnosed depression. Obesity was defined as body mass index of > or =30 kg/m(2), based on self-reported height and weight. Generalized estimating regression models were used to assess the age-adjusted association between depression and obesity. Univariate and bivariate structural equation models estimated the components of variance attributable to genetic and environmental influences. We found a modest phenotypic association between depression and obesity (odds ratio=1.6, 95% confidence interval=1.2-2.1). Additive genetic effects contributed substantially to depression (57%) and obesity (81%). The best-fitting bivariate model indicated that 12% of the genetic component of depression is shared with obesity. The association between depression and obesity in women may be in part due to shared genetic risk for both conditions. Future studies should examine the genetic, environmental, social, and cultural mechanisms underlying the relationship between this association.


The life-time rates of three major mood disorders and four major anxiety disorders in alcoholics and controls.
While psychiatric symptoms are common in the general population and even more prevalent in alcoholics, their clinical implications are not clear. The goal of this study was to establish the life-time rates of several independent and concurrent mood and anxiety disorders in alcoholics, controls and their relatives. Structured interviews were administered to alcoholics entering treatment, their relatives, and controls. The study was carried out in six different centers in the United States as part of the Collaborative Study on the Genetics of Alcoholism (COGA). Data were gathered from 2713 alcohol dependent subjects (probands and their alcoholic relatives) and 919 controls. The timeline-based Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) interview was administered face to face by trained, closely supervised interviewers. The life-time rates for concurrent and independent disorders were determined for three DSM-III-R major mood and four major anxiety disorders. Some form of independent mood disorder was seen during the life-time in slightly fewer alcoholics than controls (14.0% and 17.1%), but alcoholics did show higher rates of independent bipolar disorder (2.3% vs. 1.0%). The life-time rate for independent anxiety disorders was significantly higher in alcoholics than controls (9.4% vs. 3.7%), with most of the differential related to panic disorder (4.2% vs. 1.0%) and social phobia (3.2% vs. 1.4%), but no significant group differences for agoraphobia or obsessive-compulsive disorder. In general, these findings regarding mood and anxiety disorders were reflected in close relatives. The large majority of alcohol-dependent men and women in this sample did not have any of the independent mood or anxiety disorders evaluated here. However, there was evidence of enhanced risks among alcoholics for independent bipolar, panic and social phobic disorders. Studies which do not distinguish carefully between independent and concurrent mood and anxiety disorders in alcoholics are likely to report much higher rates of co-morbid psychiatric disorders than those that distinguish between the two types of syndromes.


Protective effects of ileal bypass versus administration of clofibrate on experimental hypercholesterolemia and atherosclerosis in monkeys.
This study was designed to compare the ability of distal intestinal bypass versus clofibrate administration to prevent the development of atherosclerosis and hypercholesterolemia in monkeys on a standardized atherogenic regimen. Three groups of monkeys were studied: one group was submitted to intestinal bypass, one group was fed clofibrate, and one group served as dietary controls. Serum cholesterol levels and group served as dietary controls. Serum cholesterol levels and gross atheromatous lesions were studied. Clofibrate offered moderate protection against experimental hypercholesteroiemia and atherosclerosis, but in animals with surgical bypass of the distal one third of the small intestine, the protection appeared to be more complete.


Effect of a beta-cypermethrin and emamectin benzoate pesticide mixture on reproductive toxicity in male mice in a greenhouse environment.
With the widespread use of pesticides, the resistance to pesticides of pests has gradually increased, caused mixed pesticides to become even more widely used for practical applications. To investigate the effects of mixed pesticides on reproductive health in an occupational greenhouse environment, the greenhouse environment and the characteristics of the actual application were constructed, and then the male mice were comprehensively exposed to a mixture of the beta-cypermethrin and emamectin benzoate environmental. Additionally, the effect of the beta-cypermethrin and emamectin benzoate mixture on the reproductive health of male mice was known. The results showed that with the prolongation of exposure duration, the activities of Glutathione Peroxidase (GSH-Px), Total Superoxide Dismutase (T-SOD), Lactate dehydrogenase (LDH) and Acid phosphatase (ACP) in the testes of mice gradually decreased and the activity of Malondialdehyde (MDA) gradually increased. It was also found that the apoptosis rate of murine testicular cells increased and that DNA damage occurred with prolonged exposure duration. Therefore, it can be inferred that exposure to a mixture of the pesticides beta-cypermethrin and emamectin benzoate in the greenhouse environment may have adverse effects on the reproductive health of male mice.


Acidic calponin immunoreactivity in postnatal rat brain and cultures: subcellular localization in growth cones, under the plasma membrane and along actin and glial filaments.
Acidic calponin, an F-actin-binding protein, is particularly enriched in brain, where calponin protein and mRNA are mainly expressed by neurons. The presence of calponin immunoreactivity in cultured astroglial cells has been reported, but the presence of acidic calponin in astrocytes in vivo appears equivocal. For the present study, we raised a specific polyclonal antibody against the 16-residue synthetic peptide covering the sequence E311-Q326 (EYPDEYPREYQYGDDQ) situated at the carboxy-terminal end of rat acidic calponin, and we investigated the cellular and subcellular localization of the protein in the developing central nervous system. Our results show that acidic calponin is particularly enriched in: (i) growth cones and submembranous fields of maturing cerebellar and cortical cells, where it codistributes with microfilaments and (ii) glial cells in vivo, including radial glia, glia limitans, Bergmann glia and mature astrocytes, and ex vivo, where acidic calponin strongly colocalizes with intermediate glial fibrillary acidic protein (GFAP) and vimentin filaments. Finally, up to four acidic calponin subtypes with different isoelectric point (pI) values were identified by two-dimensional gel electrophoresis of cerebellar and hippocampal extracts. The more acidic isoforms were developmentally regulated. As only one single mRNA for acidic calponin has been identified, these isoforms must reflect postsynthesis changes probably related to the particular functions of acidic calponin in maturing cells. Although brain acidic calponin's exact role remains uncertain, the present data suggest that it is involved in neuronal and glial plasticity.


[Communication about drug use in referrals, acute admissions and discharge letters].
It is critical to communicate properly about drug use across health care levels, to avoid adverse drug effects and medication errors. We have investigated communication about drug use between a hospital and the primary health care services through an assessment of referrals and discharge letters. At Innlandet Hospital Trust Gjøvik, all elective referrals to the medical outpatient clinic and discharge letters from the medical department during two periods (in 2009) were copied and anonymised. The documents were searched for information about drug use and for completeness of that information. We also assessed whether admission letters for acute admissions to the medical department included a medication list. 92 (47%) of 194 of elective referrals, and 167 (91%) of 184 of discharge letters, contained complete information about drug use. In 61 (49%) of 125 of discharge letters that contained information about altered drug use, these changes were not discussed in the medication list. Among 196 acutely admitted patients who used drugs, medication lists were missing in 76 (39%). When the admitting doctor was a regular GP the lists were missing in 10 (16%) of 63 of admissions. Proper communication about drug use seems to have low priority and patients are often admitted to and discharged from the hospital with insufficient information. Patients should have a paper version of their medication list until such information is available electronically.


Mucopyocele of the concha bullosa presenting as a large nasal mass.
Concha bullosa that is a pneumatization of the middle turbinate is a common anatomic variant; the obstruction of its ostium may lead to mucocele and even pyocele after infection of retained secretion. Although the condition is rare, mucopyocele of concha bullosa may be presented as a large nasal mass. However, the diagnosis could be suspected from its characteristic radiologic signs. We present an adolescent boy with mucopyocele of the concha bullosa.


Comparison of Acute Pain Syndrome after Surgical Interventions in the Nasal Cavity and Rhinoplasty.
Comparison of acute pain syndrome after septoplasty, rhinoplasty, and rhinoseptoplasty was carried out. It is shown that the intensity of acute pain is higher in patients after rhinoseptoplasty in the first 3-6 h after surgery.


First-principles calculations of electrical properties, structure, and phase transition of K1-xNaxNbO3 solid solutions.
The structure, total energy and orthorhombic as well as tetragonal electronic properties of K1-xNaxNbO3 (KNN) as a function of Na concentration were studied with first principles calculations. When the Na content of KNN was gradually increased the orthogonal phase transformation occurred, which produced an enhanced piezoelectric response of the tetragonal KNN. This result proved that the high d33 originated from the phase transition. The corresponding calculations reveal that the change of Nb-O bond length is the origin of distortion of Nb-O octahedral and phase transition. In addition, the calculations observed an unusual high peak of the KNN piezoelectric parameter, which showed the same trend as the experimental results.


Organizational climate profiles: Identifying meaningful combinations of climate level and strength.
According to situation strength theory, organizational climate should have a stronger effect on group behavior when members' perceptions of the climate are both unambiguous (i.e., very high or very low) and shared than when they are more ambiguous and less shared. In the organizational climate literature, this proposition is typically examined by testing the interaction between climate level (i.e., mean) and strength (i.e., variability); surprisingly, the preponderance of empirical research testing this interaction does not support this theoretical expectation. This may be because the traditional variable-centered approach fails to consider the possibility of overlooked subpopulations consisting of unique combinations of climate level and strength, creating distinct climate profiles. To address this issue, we use a group-centered conceptualization and analyses (i.e., latent profile analysis) to examine the extent to which 302 workgroups (Sample 1) and 107 organizations (Sample 2) evidence statistically and practically meaningful climate profiles. Results revealed four to six distinct climate profiles across multiple climate types were differentially associated with theoretically relevant outcomes, including objective financial measures. Consistent with situation strength theory, groups with strong and favorable profiles tended to have more positive outcomes, whereas groups with weaker, less favorable profiles tended to have less positive outcomes. In contrast, the traditional variable-centered approach was generally unsupportive of an interaction between climate level and strength. Overall, these findings provide evidence that the group-centered approach is a more sensitive statistical modeling technique for testing a fundamental tenet of situation strength theory in the context of organizational climate research. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Stem Cell Therapy: A New Therapeutic Option for Cardiovascular Diseases.
Cardiovascular diseases are known as one of major causes of morbidity and mortality worldwide. Despite the many advancement in therapies are associated with cardiovascular diseases, it seems that finding of new therapeutic option is necessary. Cell therapy is one of attractive therapeutic platforms for treatment of a variety of diseases such as cardiovascular diseases. Among of various types of cell therapy, stem cell therapy has been emerged as an effective therapeutic approach in this area. Stem cells divided into multipotent stem cells and pluripotent stem cells. A large number studies indicated that utilization of each of them are associated with a variety of advantages and disadvantages. Multiple lines evidence indicated that stem cell therapy could be used as suitable therapeutic approach for treatment of cardiovascular diseases. Many clinical trials have been performed for assessing efficiency of stem cell therapies in human. However, stem cell therapy are associated with some challenges, but, it seems resolving of them could contribute to using of them as effective therapeutic approach for patients who suffering from cardiovascular diseases. In the current review, we summarized current therapeutic strategies based on stem cells for cardiovascular diseases. J. Cell. Biochem. 119: 95-104, 2018. © 2017 Wiley Periodicals, Inc.


Promoting safer home environments for persons with Alzheimer's disease. The Home Safety/Injury Model.
This article describes a Home Safety/Injury Model derived from Social Cognitive Theory. The model's three components are safety platform, the person with dementia, and risky behaviors. The person with dementia is in the center, located on the safety platform composed of the physical environment and caregiver competence. The interaction between the underlying dementia and indicators of frailty can lead to the person with dementia performing risky behaviors that can overcome the safety platform's resources and lead to an accident or injury, and result in negative consequences. Through education and research, the model guides proactive actions to prevent risky behaviors of individuals with dementia by promoting safer home environments and increased caregiver competence.


Thermal collapse and hierarchy of polymorphs in a faujasite-type zeolite and its analogous melt-quenched glass.
We examine the route of structural collapse and re-crystallization of faujasite-type (Na,K)-LSX zeolite. As the first step, a rather stable amorphous high density phase HDAcollapse is generated through an order-disorder transition from the original zeolite via a low density phase LDAcollapse, at around 790 °C. We find that the overall amorphization is driven by an increase in the bond angle distribution within T-O-T and a change in ring statistics to 6-membered TO4 (T = Si(4+), Al(3+)) rings at the expense of 4-membered rings. The HDAamorph transforms into crystalline nepheline, though, through an intermediate metastable carnegieite phase. In comparison, the melt-derived glass of similar composition, HDAMQ, crystallizes directly into the nepheline phase without the occurrence of intermediate carnegieite. This is attributed to the higher structural order of the faujasite-derived HDAcollapse which prefers the re-crystallization into the highly symmetric carnegieite phase before transformation into nepheline with lower symmetry.


[Influence of exposure to immobilisation stress on blood concentration of TNF alpha and IL-4 in rats active and passive in the open field test].
The influence of exposure to immobilization stress on TNF alpha and IL-4 concentrations in blood was studied in behaviorally active vs. passive in the open field Wistar rats. One hour after exposure to stress, blood concentrations of TNF alpha and IL-4 were significantly lower in behaviorally passive as compared to active rats and passive controls not exposed to stress. Moreover, in passive rats exposed to stress, the pituitary weight increased as compared to passive controls. Behaviorally passive rats exposed to emotional stress were characterized by a decreased blood levels of TNF alpha and IL-4 as compared to behaviorally passive controls and behaviorally active animals exposed to stress.


[Mobilization of the pACYC184 plasmid by hybrid pAS8-121 delta plasmids in Escherichia coli cells].
The plasmid pACYC184 is shown to be mobilized for conjugal transfer in Escherichia coli cells by the deleted (Tn7-TcR) derivatives of the hybrid conjugative plasmid pAS8-121 (RP4-Co1E1). Both the mobilized and mobilizing plasmids are autonomously inherited by the recipient cells when the mobilizing plasmid carries single copy of IS8 (the plasmid pAS8-121 delta 16). Cointegrates pAS8-121 delta 16D:: ::pACYC184 are found in the recipient cells with pACYC184 being inserted between two repeats of IS8 if the derivate plasmid pAS8-121 delta 16D having the duplication of IS8 is used to mobilize pACYC184 for conjugal transfer. The insertion of pACYC184 between IS8 repeats in the plasmid pAS8-121 delta 16D eliminates the plasmid ability to be inserted with high frequency into the chromosome of the phototrophic bacterium R. sphaeroides 2R. The cointegrate pAS8-121 delta 16D:: pACYC184 is stable but can be resolved during the transformation deriving the plasmid pACYC184:: IS8. The latter may be used as a probe for isolation and analysis of IS8 DNA sequences and for constructing the vectors on the basis of pACYC184.


Blind equalization of a noisy channel by linear neural network.
In this paper, a new neural approach is introduced for the problem of blind equalization in digital communications. Necessary and sufficient conditions for blind equalization are proposed, which can be implemented by a two-layer linear neural network. In the hidden layer, the received signals are whitened, while the network outputs provide directly an estimation of the source symbols. We consider a stochastic approximate learning algorithm for each layer according to the property of the correlation matrices of the transmitted symbols. The proposed class of networks yield good results in simulation examples for the blind equalization of a three-ray multipath channel.


Morbidity and Mortality of Mississippi Kites (Ictinia mississippiensis) Presenting to the Wildlife Hospital of Louisiana, USA.
A review of hospital admissions for Mississippi Kites (Ictinia mississippiensis) 2014-20 found that most admissions were due to trauma, including ballistic trauma. Overall, 118/ 282 (42%) survived, including releases and transfers. This baseline data may enable earlier detection of epidemics and of human-animal conflict escalation in other kite populations.


Reactome and the Gene Ontology: digital convergence of data resources.
Gene Ontology Causal Activity Models (GO-CAMs) assemble individual associations of gene products with cellular components, molecular functions and biological processes into causally linked activity flow models. Pathway databases such as the Reactome Knowledgebase create detailed molecular process descriptions of reactions and assemble them, based on sharing of entities between individual reactions into pathway descriptions. To convert the rich content of Reactome into GO-CAMs, we have developed a software tool, Pathways2GO, to convert the entire set of normal human Reactome pathways into GO-CAMs. This conversion yields standard GO annotations from Reactome content and supports enhanced quality control for both Reactome and GO, yielding a nearly seamless conversion between these two resources for the bioinformatics community. Supplementary data are available at Bioinformatics online.


MAOA interacts with the ALDH2 gene in anxiety-depression alcohol dependence.
Alcohol dependence is usually comorbid with anxiety disorder, depressive disorder, or both; this comorbidity may increase drinking behavior. We previously hypothesized that anxiety-depressive alcohol dependence (ANX/DEP ALC) was a genetically specific subtype of alcohol dependence. ANX/DEP ALC may be related to dopamine and serotonin, which are catalyzed by monoamine oxidase A (MAOA) and acetaldehyde dehydrogenase 2 (ALDH2). The aim of this study was to determine whether the interaction between the MAOA and the ALDH2 genes is associated with ANX/DEP ALC. We recruited 383 Han Chinese men in Taiwan: 143 ANX/DEP ALC and 240 healthy controls. The diagnosis of ANX/DEP ALC (alcohol dependence with a past or current history of anxiety, depressive disorder, or both) was made using DSM-IV criteria. Genotypes of ALDH2 and MAOA-uVNTR (variable number of tandem repeat located upstream) were determined using PCR-RFLP. The ALDH2, but not the MAOA-uVNTR, polymorphism was associated with ANX/DEP ALC. After stratifying the MAOA-uVNTR polymorphism, we found a stronger association between the ALDH2*1/*2 and *2/*2 genotypes and the controls in the MAOA-uVNTR 4-repeat subgroup. Logistic regression significantly associated the interaction between ALDH2 and MAOA variants with ANX/DEP ALC. We conclude that the MAOA and ALDH2 genes interact in ANX/DEP ALC. Although the MAOA gene alone is not associated with ANX/DEP ALC, we hypothesize that different variants of MAOA-uVNTR polymorphisms modify the protective effects of the ALDH2*2 allele on ANX/DEP ALC in Han Chinese in Taiwan.


A comparison of avian and rodent S-9 liver homogenates in the Ames test.
Avian S-9 liver homogenates were obtained from phenobarbital, 3-methylcholanthrene (3-MC), polychlorinated biphenyl (Aroclor 1254) induced and control chickens. These homogenates were tested for their capacity to metabolically activate benzo[a]pyrene (B[a]P) and cyclo-phosphamide in the Salmonella typhimurium assay. Liver homogenates from 3-MC, Aroclor 1254 and phenobarbital induced chickens were more active in converting B[a]P to its ultimate mutagenic form than was S-9 obtained from Aroclor 1254 induced rats. However, Aroclor 1254 induced rat S-9 was superior to Aroclor 1254 induced avian S-9 in metabolically activating cyclophosphamide.


The role of branched-chain aminotransferase 1 in driving glioblastoma cell proliferation and invasion varies with tumor subtype.
Branched-chain aminotransferase 1 (BCAT1) has been proposed to drive proliferation and invasion of isocitrate dehydrogenase (IDH) wild-type glioblastoma cells. However, the Cancer Genome Atlas (TCGA) dataset shows considerable variation in the expression of this enzyme in glioblastoma. The aim of this study was to determine the role of BCAT1 in driving the proliferation and invasion of glioblastoma cells and xenografts that have widely differing levels of BCAT1 expression and the mechanism responsible. The activity of BCAT1 was modulated in IDH wild-type patient-derived glioblastoma cell lines, and in orthotopically implanted tumors derived from these cells, to examine the effects of BCAT1 expression on tumor phenotype. In cells with constitutively high BCAT1 expression and a glycolytic metabolic phenotype, inducible shRNA knockdown of the enzyme resulted in reduced proliferation and invasion by increasing the concentration of α-ketoglutarate, leading to reduced DNA methylation, HIF-1α destabilization, and reduced expression of the transcription factor Forkhead box protein M1 (FOXM1). Conversely, overexpression of the enzyme increased HIF-1α expression and promoted proliferation and invasion. However, in cells with an oxidative phenotype and very low constitutive expression of BCAT1 increased expression of the enzyme had no effect on invasion and reduced cell proliferation. This occurred despite an increase in HIF-1α levels and could be explained by decreased TCA cycle flux. There is a wide variation in BCAT1 expression in glioblastoma and its role in proliferation and invasion is dependent on tumor subtype.


CD24 negative lung cancer cells, possessing partial cancer stem cell properties, cannot be considered as cancer stem cells.
Cancer stem cells (CSCs) play vital role in lung cancer progression, resistance, metastasis and relapse. Identifying lung CSCs makers for lung CSCs targeting researches are critical for lung cancer therapy. In this study, utilizing previous identified lung CSCs as model, we compared the expression of CD24, CD133 and CD44 between CSCs and non-stem cancer cells. Increased ratio of CD24- cells were found in CSCs. CD24- cells were then sorted by flow cytometry and their proliferative ability, chemo-resistance property and in vivo tumor formation abilities were detected. A549 CD24- cells formed smaller colonies, slower proliferated in comparison to A549 CD24+ cells. Besides, A549 CD24- exhibited stronger resistance to chemotherapy drug. However, A549 CD24- didn't exert any stronger tumor formation ability in vivo, which is the gold standard of CSCs. These results showed that CD24- A549 cells showed some properties of CSCs but not actually CSCs. This study provides evidence that CD24 cannot be considered as lung CSCs marker.


Evaluation of Endothelial Function by Flow-Mediated Dilation: a Comprehensive Review in Rheumatic Disease.
Flow-mediated dilation (FMD) represents a non-invasive marker of endothelial function to evaluate vascular homeostasis, which reflects the effects of several mechanisms, including vessel tone regulation, cell proliferation, and inflammatory responses. Beyond classical atherosclerotic risk factors such as arterial hypertension, diabetes mellitus, smoking, obesity, and dyslipidemia, chronic inflammation contributes to the endothelial dysfunction causing plaque formation and there is growing evidence of a significantly higher cardiovascular morbidity associated with autoimmune diseases. The endothelium reacts to several endogenous and exogenous stimuli, through surface receptors and intracellular signalling, and releases numerous vasoactive substances, including endothelins, prostacyclins, and nitric oxide (NO). Chronic inflammatory rheumatic diseases are commonly associated with decreased endothelial NO production, vascular damage, and premature atherosclerosis. Despite partially eclipsed by pulse wave velocity measure in the modern scientific literature, we provide a comprehensive overview and critically discuss the available data supporting FMD as a surrogate marker of endothelial function and, therefore, its potential role in predicting early atherosclerosis in patients with rheumatic diseases.


First Things First: Difficulty with Current Medications Is Associated With Patient Willingness to Add New Ones.
BACKGROUND: Inadequate blood pressure (BP) control remains prevalent. One proposed explanation is "clinical inertia," often defined as the failure by providers to initiate or intensify medication therapy when otherwise appropriate. However, patients could contribute to clinical inertia by signaling an unwillingness to consider medication intensification. OBJECTIVE: To explore covariates of patient attitudes regarding medication intensification. STUDY DESIGN: Cross-sectional survey. SETTING: 9 Midwestern U. S. Veterans' Administration medical facilities. PARTICIPANTS: 1,062 diabetics identified as having BP>= 140/90 mm Hg as part of a prospective cohort study of clinical inertia in hypertension treatment. MEASUREMENTS: Primary outcome was participants' indicated willingness to intensify BP medications if their provider noted elevated BP levels. Potential covariates assessed included BP control (actual and perceived), perceived importance of BP control, BP management self-efficacy, competing demands, medication factors (adherence and management issues), trust in provider, and sociodemographic factors. RESULTS: While 64% of participants reported complete willingness to intensify BP medications, 36% of participants expressed at least some unwillingness. In ordered logistic regression analysis, willingness to intensify was negatively associated with medication concerns, particularly concern about side effects (OR=0.49, 95% CI: 0.42, 0.59) and adherence or management problems (OR=0.72, 95% CI: 0.57, 0.91), and positively associated with perceived dependence of health on BP medications (OR=1.50, 95% CI: 1.26, 1.79) and trust in provider (OR=1.30, 95% CI: 1.10, 1.54). Importance of BP control had a weaker, non-significant association with willingness to intensify as well (OR=1.17, 95% CI: 0.99, 1.40). Neither competing demands, current BP control, current number of medications prescribed, nor self-efficacy was associated with willingness to intensify medications. CONCLUSIONS: Patients' willingness to consider intensification of BP medications appears primarily determined by how well patients are managing their current medications, rather than patients' perceived importance of BP control, their self-efficacy, or their prioritization of BP control versus other health demands. Greater attention to patients' pre-existing medication issues may improve providers' ability to intensify BP medication therapy when medically appropriate while simultaneously improving patient satisfaction with care.


The associations among eNOS G894T gene polymorphism, erectile dysfunction, and benign prostate hyperplasia-related lower urinary tract symptoms.
A number of literature has now identified the role of impaired nitric oxide synthase/nitric oxide pathway in the endothelium as the central to the development of erectile dysfunction (ED) and benign prostate hyperplasia-related lower urinary tract symptoms (BPH/LUTS). Recently a few studies have reported the associations between endothelial nitric oxide synthase (eNOS) G894T gene polymorphisms and ED. However, there has been no report investigating the eNOS G894T genetic susceptibility factor for both ED and BPH/LUTS. To investigate the possible associations among eNOS G894T polymorphism, ED, and BPH/LUTS in a Taiwanese population. Patients with ED were defined as those having a 5-item International Index of Erectile Function-5 <21. In all, 372 Taiwanese men underwent a free health screening were enrolled. All the men had complete clinical data and questionnaires taken. The eNOS G894T polymorphisms were determined using the polymerase chain reaction-restriction fragment length polymorphism method. Three hundred seventy-two men had a mean (standard deviation) age of 60.2 (8.8) years. With multivariate analysis, our data identified that aging, diabetes mellitus (DM), and eNOS G894T gene polymorphism were three independent common risk factors for both ED and BPH/LUTS (P < 0.001, P = 0.036, and P = 0.039 for ED; P = 0.034, P = 0.004, and P = 0.016 for BPH/LUTS, respectively). The eNOS 894T allele carriers had significantly higher prevalence of ED (77.9% vs. 60.4%, P = 0.012) and higher International Prostate Symptom score (IPSS) (13.3 +/- 10.7 vs. 9.3 +/- 7.8, P = 0.001) than G allele carriers. Our results showed that aging, DM, and eNOS 894T allele carrier gene polymorphism were the three independently common risk factors for both ED and BPH/LUTS in the Taiwanese population. The eNOS 894T allele carriers had significantly higher frequencies of ED and higher IPSS, suggesting that eNOS G894T gene polymorphisms may play an implication as a genetic susceptibility factor for both ED and BPH/LUTS.


Total and occupationally active life expectancies in relation to social class and marital status in men classified as healthy at 20 in Finland.
To study differences in total life expectancy and in occupationally active life expectancy in relation to social class and marital status in men classified as healthy as young adults. Historical cohort study. Finland. Altogether 1662 men classified as completely healthy at the time of induction to military service (mean birth year 1923), who had been selected as referents for a study of former athletes. Mean follow up time was 46 years. Vital status was determined by follow up through local parish data up to 1990. Mortality data were obtained from the Cause of Death bureau of the Central Statistical Office of Finland. Occurrence of work disability was assessed from nationwide disability pension register data. Mean total life expectancy and mean occupationally active life expectancy (end points disability pension or death before age 65 years) were estimated. Social class was based on the major lifetime occupation, while marital status was classified as "never married" or "ever married" at the end of follow up. Mean total life expectancy was highest among executives and managers (73.2 (95% confidence interval (CI): 70.3, 76.1) years), next highest in clerical (white collar) workers (72.0 (70.0, 74.1) years), and lowest in unskilled blue collar workers (63.65 (61.1, 66.2) years). Skilled workers and farmers were intermediate. For the occupationally active life expectancy estimates, a similar gradient was observed: highest for executives (61.9 (60.7, 63.1) years) and lowest for the unskilled (52.2 (50.2, 54.2) years). The ratio of occupationally active life expectancy to total life expectancy was highest for executives (85%) and lowest for farmers (81%) and unskilled workers (82%). The social class gradient known to exist for mortality is also present for occupational disability. Social class and marital status differences in mortality are already evident in early adulthood and continue into old age. Those with the highest life expectancy also have the largest proportion of their life span free of occupationally incapacitating disability.


Plasticity of the electric organ discharge waveform of the electric fish Brachyhypopomus pinnicaudatus. I. Quantification of day-night changes.
The electric organ discharge of the gymnotiform fish Brachyhypopomus pinnicaudatus is a biphasic waveform. The female's electric organ discharge is nearly symmetric but males produce a longer second phase than first phase. In this study, infrared-sensitive video cameras monitored the position of unrestrained fish, facilitating precise measurement of electric organ discharge duration and amplitude every 2 h for 24 h. Males (n = 27) increased electric organ discharge duration by 37 +/- 12% and amplitude by 24 +/- 9% at night and decreased it during the day. In contrast, females (n = 8) exhibited only minor electric organ discharge variation over time. Most of a male's increase occurred rapidly within the first 2-3 h of darkness. Electric organ discharge values gradually diminished during the second half of the dark period and into the next morning. Modulation of the second phase of the biphasic electric organ discharge produced most of the duration change in males, but both phases changed amplitude by similar amounts. Turning the lights off at mid-day triggered an immediate increase in electric organ discharge, suggesting modification of existing ion channels in the electric organ, rather than altered genomic expression. Exaggeration of electric organ discharge sex differences implies a social function. Daily reduction of duration and amplitude may reduce predation risk or energy expenditure.


Mentoring for postdoctoral researchers in rheumatology: the Emerging EULAR Network (EMEUNET) post-doc mentoring programme.
This study aims to (1) assess the perceived need for a postdoctoral (post-doc) mentoring programme in rheumatology, (2) describe the characteristics and organisational aspects of a pilot mentoring programme implemented by the EMerging European League Against Rheumatism NETwork (EMEUNET) and (3) report mentors' and mentees' evaluation of the pilot programme. An online survey was conducted among young researchers in rheumatology to evaluate the need and preferred characteristics of a post-doc mentoring initiative. Informed by the survey, a pilot programme was designed and launched. The pilot programme was evaluated with 3-month, 6-moth and 12-month surveys and interviews with mentees and a 12-month survey among mentors, after completion. From 275 responses (43 countries, 86% from Europe) collected, analyses were restricted to the target population (total population=158; post-docs (n=103 (65%)) and PhD students (n=55 (35%))). There was a clear need (99% positive responses) for a post-doc mentoring programme. Discussions about current and new projects, and how to lead projects were ranked as priorities in post-doc mentoring. The most desired mentor attribute was generosity and interest in helping (86%), followed by research experience (68%) and having a well-established network (66%). The pilot programme included four mentees (through competitive application) allocated to three mentors. Evaluation surveys and interviews revealed that the programme organisation and content were well appreciated by mentees and mentors. The EMEUNET post-doc mentoring programme addresses unmet need for mentoring, is viable and appreciated by mentors and mentees. The programme structure and content are transferable to other fields where there is need for academic career mentoring.


Effects of phencyclidine on ventral tegmental A10 dopamine neurons in the rat.
Extracellular single unit recordings were used to determine the effects of systemically and iontophoretically applied phencyclidine on electrophysiologically-identified A10 dopamine neurons within the ventral tegmental area of the rat. Intravenous injections of phencyclidine inhibited, as well as excited A10 cells. Approximately 42% of the inhibitions induced by phencyclidine were completely reversed by an injection of haloperidol. The excitatory effects of phencyclidine most often resulted in a state of depolarized inactivation and were not sensitive to haloperidol. The alteration of the activity of A10 cells by systemically-applied phencyclidine was effectively prevented in all animals pretreated with a combination of reserpine and alpha-methyl-p-tyrosine, which depleted stores of central catecholamines by over 90%. In contrast to the data obtained with intravenous injections, iontophoretic applications of phencyclidine produced only inhibition of the activity of the A10 cells and, in a few of these cases the decreased firing rate was accompanied by an increase in the amplitude of the action potential. A comparison of the response patterns of dopaminergic neurons to systemically- and iontophoretically-applied phencyclidine would suggest that excitations induced by phencyclidine are not mediated at the level of the A10 cell bodies but through a site outside the ventral tegmental area. The results of this study also indicate that some of the effects of phencyclidine on the activity of A10 neurons are clearly dependent upon an interaction with dopamine and thus, would support the hypothesis that phencyclidine can act as an indirect dopamine agonist. However, other effects of phencyclidine which are not apparently linked to dopamine may represent the response of a pharmacologically-distinct subpopulation of A10 neurons to phencyclidine.


The trimerization of acetylenes involves a cascade of biradical and pericyclic processes.
Thorough computational studies were performed on mechanisms and energies for the thermal trimerizations of neutral or electron-rich acetylenes used as cross-linkers in organic hard-masks for lithography applications. These studies indicate that the operative mechanism proceeds through initial cyclobutadiene formation via a biradical mechanism. Cyclobutadienes form Dewar benzenes via Diels-Alder cycloadditions, or biradical processes, or both, before producing benzenes by electrocyclic ring-opening reactions. These pathways are preferred to alternatives involving concerted trimerizations or mechanisms involving carbene intermediates.


Polyphenols Epigallocatechin Gallate and Resveratrol, and Polyphenol-Functionalized Nanoparticles Prevent Enterovirus Infection through Clustering and Stabilization of the Viruses.
To efficiently lower virus infectivity and combat virus epidemics or pandemics, it is important to discover broadly acting antivirals. Here, we investigated two naturally occurring polyphenols, Epigallocatechin gallate (EGCG) and Resveratrol (RES), and polyphenol-functionalized nanoparticles for their antiviral efficacy. Concentrations in the low micromolar range permanently inhibited the infectivity of high doses of enteroviruses (107 PFU/mL). Sucrose gradient separation of radiolabeled viruses, dynamic light scattering, transmission electron microscopic imaging and an in-house developed real-time fluorescence assay revealed that polyphenols prevented infection mainly through clustering of the virions into very stable assemblies. Clustering and stabilization were not compromised even in dilute virus solutions or after diluting the polyphenols-clustered virions by 50-fold. In addition, the polyphenols lowered virus binding on cells. In silico docking experiments of these molecules against 2- and 3-fold symmetry axes of the capsid, using an algorithm developed for this study, discovered five binding sites for polyphenols, out of which three were novel binding sites. Our results altogether suggest that polyphenols exert their antiviral effect through binding to multiple sites on the virion surface, leading to aggregation of the virions and preventing RNA release and reducing cell surface binding.


Mars' paleomagnetic field as the result of a single-hemisphere dynamo.
Mars' crustal magnetic field was most likely generated by dynamo action in the planet's early history. Unexplained characteristics of the field include its strength, concentration in the southern hemisphere, and lack of correlation with any surface features except for the hemispheric crustal dichotomy. We used numerical dynamo modeling to demonstrate that the mechanisms proposed to explain crustal dichotomy formation can result in a single-hemisphere dynamo. This dynamo produces strong magnetic fields in only the southern hemisphere. This magnetic field morphology can explain why Mars' crustal magnetic field intensities are substantially stronger in the southern hemisphere without relying on any postdynamo mechanisms.


Functional disability in paediatric patients with recurrent abdominal pain.
Recurrent abdominal pain (RAP) is common in childhood, affecting approximately 12% of children and adolescents. Children with RAP tend to experience impairments in functioning, such as increased school absences, anxiety and depression. The current study investigated the potential influences on the relation between functional disability and RAP in 100 school-aged children. A series of hierarchical regression analyses were conducted to test two models: main effects and moderation of the relation between abdominal pain symptoms, child anxiety, child depression, maternal emotional distress, maternal encouragement of child illness behaviour and functional disability. The results indicated support for abdominal pain symptoms and child depression in predicting functional disability. The results also indicated that child anxiety and child depression each moderated the relation between pain symptoms and functional disability. Implications of the findings are discussed in terms of potential influences on the development of functional disability in youth.


Physiology of peripheral neurons innervating otolith organs of the squirrel monkey. III. Response dynamics.
1. The discharge of peripheral otolith neurons in response to sinusoidal force variations was investigated in the barbiturate-anesthetized squirrel monkey (Saimiri sciureus). The sine waves were superimposed on a background force which biased the end organ so as to excite or inhibit the unit's firing. Both regularly and irregularly discharging neurons were studied. 2. The response amplitude, measured as a peak-to-peak changes in firing rate, reached near-maximal values during the first sine-wave cycle and, for most units, remained constant as sinusoidal stimulation was prolonged. 3. In regular units, introduction of an excitatory bias increased the sensitivity to sinusoidal stimulation in a manner consistent with the static asymmetries observed in the response to constant forces. Bias effects in irregular units were usually small and, in some cases, excitatory biases resulted in a decrease in sensitivity. 4. Variation in sine-wave amplitude had no effect on the sinusoidal gains or phases of regular units. For irregular units, there was some evidence of a small gain increase as stimulus amplitude decreased. 5. Nonlinear distortion was usually 10-20% and was mainly of an asymmetric type. In regular units, the distortion could be partially related to static asymmetries. 6. The response of regular units is predominantly tonic, that of irregular units more phasic. For regular units there was usually no more than a twofold gain enhancement as frequency was increased in the spectrum from DC to 2.0 Hz; typically, small phase leads at low frequencies were replaced by similar phase lags at higher frequencies. Irregular units were characterized by a 20-fold frequency-dependent gain enhancement over the same spectrum; phase leads of 20-40% were seen. 7. Bodeplots were fit by a family of transfer functions, each consisting of three terms. The first is a velocity-sensitive operator with a fractional exponent. The second is a low-frequency adaptation operator. Only the lag operator can be related to the dynamics of otoligh motion. Most of the variations among units, including those seen between regular and irregular units, can be accounted for by suitable variations in the velocity-sensitive and adaptation operators. 8. The transfer functions, when integrated and inverted, led to reasonable approximations of the response to force trapezoids. It is concluded that the transfer functions provide an adequate representation of the dynamic behavior of most units. The only exceptions are the few neurons showing delayed adaptation.


Elemental metals for environmental remediation: learning from cementation process.
The further development of Fe(0)-based remediation technology depends on the profound understanding of the mechanisms involved in the process of aqueous contaminant removal. The view that adsorption and co-precipitation are the fundamental contaminant removal mechanisms is currently facing a harsh scepticism. Results from electrochemical cementation are used to bring new insights in the process of contaminant removal in Fe(0)/H(2)O systems. The common feature of hydrometallurgical cementation and metal-based remediation is the heterogeneous nature of the processes which inevitably occurs in the presence of a surface scale. The major difference between both processes is that the surface of remediation metals is covered by layers of own oxide(s) while the surface of the reducing metal in covered by porous layers of the cemented metal. The porous cemented metal is necessarily electronic conductive and favours further dissolution of the reducing metal. For the remediation metal, neither a porous layer nor a conductive layer could be warrant. Therefore, the continuation of the remediation process depends on the long-term porosity of oxide scales on the metal surfaces. These considerations rationalized the superiority of Fe(0) as remediation agent compared to thermodynamically more favourable Al(0) and Zn(0). The validity of the adsorption/co-precipitation concept is corroborated.


Resonance energy transfer imaging of phospholipid vesicle interaction with a planar phospholipid membrane: undulations and attachment sites in the region of calcium-mediated membrane--membrane adhesion.
Membrane fusion of a phospholipid vesicle with a planar lipid bilayer is preceded by an initial prefusion stage in which a region of the vesicle membrane adheres to the planar membrane. A resonance energy transfer (RET) imaging microscope, with measured spectral transfer functions and a pair of radiometrically calibrated video cameras, was used to determine both the area of the contact region and the distances between the membranes within this zone. Large vesicles (5-20 microns diam) were labeled with the donor fluorophore coumarin-phosphatidylethanolamine (PE), while the planar membrane was labeled with the acceptor rhodamine-PE. The donor was excited with 390 nm light, and separate images of donor and acceptor emission were formed by the microscope. Distances between the membranes at each location in the image were determined from the RET rate constant (kt) computed from the acceptor:donor emission intensity ratio. In the absence of an osmotic gradient, the vesicles stably adhered to the planar membrane, and the dyes did not migrate between membranes. The region of contact was detected as an area of planar membrane, coincident with the vesicle image, over which rhodamine fluorescence was sensitized by RET. The total area of the contact region depended biphasically on the Ca2+ concentration, but the distance between the bilayers in this zone decreased with increasing [Ca2+]. The changes in area and separation were probably related to divalent cation effects on electrostatic screening and binding to charged membranes. At each [Ca2+], the intermembrane separation varied between 1 and 6 nm within each contact region, indicating membrane undulation prior to adhesion. Intermembrane separation distances < or = 2 nm were localized to discrete sites that formed in an ordered arrangement throughout the contact region. The area of the contact region occupied by these punctate attachment sites was increased at high [Ca2+]. Membrane fusion may be initiated at these sites of closest membrane apposition.


Reproducibility of LCA models of crude oil production.
Scientific models are ideally reproducible, with results that converge despite varying methods. In practice, divergence between models often remains due to varied assumptions, incompleteness, or simply because of avoidable flaws. We examine LCA greenhouse gas (GHG) emissions models to test the reproducibility of their estimates for well-to-refinery inlet gate (WTR) GHG emissions. We use the Oil Production Greenhouse gas Emissions Estimator (OPGEE), an open source engineering-based life cycle assessment (LCA) model, as the reference model for this analysis. We study seven previous studies based on six models. We examine the reproducibility of prior results by successive experiments that align model assumptions and boundaries. The root-mean-square error (RMSE) between results varies between ∼1 and 8 g CO2 eq/MJ LHV when model inputs are not aligned. After model alignment, RMSE generally decreases only slightly. The proprietary nature of some of the models hinders explanations for divergence between the results. Because verification of the results of LCA GHG emissions is often not possible by direct measurement, we recommend the development of open source models for use in energy policy. Such practice will lead to iterative scientific review, improvement of models, and more reliable understanding of emissions.


Photobiomodulation therapy in neuroischaemic diabetic foot ulcers: a novel method of limb salvage.
Low-level laser therapy (also known as photobiomodulation therapy, PBMT) promotes accelerated healing of diabetic foot ulcers (DFUs), thereby preventing the risk of future complications and amputation. The aim of this study was to determine the effect of PBMT, with structured, graded mobilisation and foot care, on DFU healing dynamics. Patients diagnosed with type 2 diabetes, diabetic peripheral neuropathy and presenting with a chronic neuroischaemic DFU, were treated with PBMT using scanning and non-contact probe methods. The DFU was clinically observed and the area measured every seven days until complete healing. Neuropathic parameters were also measured. The PBMT was administered until complete closure of the DFU and patients also undertook a programme of graded mobilisation. A total of 17 participants were recruited, with a mean age of 69±8 years, and a mean duration of diabetes of 13±5 years. Mean complete closure time was 26±11days. In addition, a mean reduction of the semi-quantitative vibration pressure threshold from 49±2 volts to 20±4 volts was observed in all participants. PBMT can be effectively used as a treatment mode for neuroischaemic DFUs in patients with type 2 diabetes. Graded mobilisation with focused foot care could improve the function of people living with type 2 diabetes with a chronic DFU.


Non-covalent hitchhiking on endogenous carriers as a protraction mechanism for antiviral macromolecular prodrugs.
Albumin is a highly successful tool of drug delivery providing drastically extended body and blood residence time for the associated cargo, but it only traffics single drug copies at a time. In turn, macromolecular prodrugs (MP) are advantaged in carrying a high drug payload but offering only a modest extension of residence time to the conjugated drugs. In this work, we engineer MP to contain terminal groups that bind to albumin via non-covalent association and reveal that this facile measure affords a significant protraction for the associated polymers. This methodology is applied to MP of acyclovir, a successful drug against herpes simplex virus infection but with poor pharmacokinetics. Resulting albumin-affine MP were efficacious agents against herpes simplex virus type 2 (HSV-2) both in vitro and in vivo. In the latter case, sub-cutaneous administration of MP resulted in local (vaginal) antiviral effects and a systemic protection. Presented benefits of non-covalent association with albumin are readily transferrable to a wide variety of MP in development for drug delivery as anticancer, anti-inflammatory, and anti-viral measures.


Silibinin triggers yeast apoptosis related to mitochondrial Ca2+ influx in Candida albicans.
Candida albicans is a common yeast that resides in the human body, but can occasionally cause systemic fungal infection, namely candidiasis. As this infection rate is gradually increasing, it is becoming a major problem to public health. Accordingly, we for the first time investigated the antifungal activity and mode of action of silibinin, a natural product extracted from Silybum marianum (milk thistle), against C. albicans. On treatment with 100μM silibinin, generation of reactive oxygen species (ROS) from mitochondria, which can cause yeast apoptosis via oxidative stress, was increased by 24.17% compared to that in untreated cells. Subsequently, we found disturbances in ion homeostasis such as release of intracellular K+ and accumulation of cytoplasmic and mitochondrial Ca2+. Among these phenomena, mitochondrial Ca2+ overload particularly plays a crucial role in the process of apoptosis, promoting the activation of pro-apoptotic factors. Therefore, we investigated the significance of mitochondrial Ca2+ in apoptosis by employing 20mM ruthenium red (RR). Additional apoptosis hallmarks such as mitochondrial membrane depolarization, cytochrome c release, caspase activation, phosphatidylserine (PS) exposure, and DNA damage were observed in response to silibinin treatment, whereas RR pre-treatment seemed to block these responses. In summary, our results suggest that silibinin induces yeast apoptosis mediated by mitochondrial Ca2+ signaling in C. albicans.


Productive performance, breast growth and digestive system development in European quail subjected to post-hatch fasting for different periods.
This study assessed the effect of different periods of post-hatch fasting on animal performance and breast and digestive system growth in European quail. Quail chicks were distributed in a completely randomized design, with four fasting periods (0, 24, 36, and 48 hs) and four replications of 40 birds per treatment. In 1 to 14-day-old chicks, weight gain decreased with increasing fasting time. Compensatory gain was observed from 15 days of age onward. Fasted quail had a lower length and relative weight of the digestive system than fed animals for up to 14 days. Histologically, the duodenal villus height was significantly lower in 3-day-old quail fasted for 36 hs than in those fasted for 48 hs, but this effect was not observed at 7 days. Scanning electron microscopy showed no differences in the small intestinal mucosa between fasted and fed birds at 3 days of age. Post-hatch fasting reduced the relative weight of the breast in quail aged 1 to 14 days but did not affect type IIa and IIb fiber diameter at 35 days. On the basis of these results, it is recommended that European quail raised for meat should not be fasted for more than 48 hs post-hatch.


Prospective evaluation of pancreatic tumors: accuracy of MR imaging with MR cholangiopancreatography and MR angiography.
To prospectively assess accuracy of magnetic resonance (MR) imaging, MR cholangiopancreatography (MRCP), and MR angiography in patients suspected of having pancreatic tumors. Sixty-six patients suspected of having pancreatic tumors underwent MR imaging (unenhanced and contrast material-enhanced MR, MRCP, and contrast-enhanced MR angiography). Two blinded readers prospectively analyzed the images by consensus, and results were correlated with surgery, biopsy, or follow-up findings. Results were tabulated in two-by-two tables. MR assessment of pancreatic lesion status (differentiation of benign vs malignant) resulted in 60 correct diagnoses (accuracy, 91%), and six (10%) false diagnoses. Among histologically proved malignant tumors, MR imaging yielded correct diagnoses in 42 of 44 patients (sensitivity, 95%; 95% CI: 85%, 99%), whereas 18 of 22 patients with benign findings were classified correctly. At MR imaging, findings in four patients with chronic pancreatitis were wrongly categorized as malignant tumors (specificity, 82%; 95% CI: 60%, 95%), and in one patient, a distal common bile duct carcinoma was not detected. In no patient with pancreatic adenocarcinoma was this tumor misdiagnosed as benign. In patients with malignant tumors who underwent resection, local-regional tumor growth and vascular infiltration were accurately classified in 89% and 94%, respectively. MR imaging depicted histologically proved synchronous hepatic metastases in 82%. The positive and negative predictive values for cancer nonresectability were 90% and 83%, respectively, and the accuracy, sensitivity, and specificity were 85%, 69%, and 95%, respectively. Unenhanced and contrast-enhanced MR imaging with MRCP and MR angiography offers potential as a noninvasive tool for assessment of patients suspected of having pancreatic tumors.


Evaluation of the Dual Path Platform (DPP) VetTB assay for the detection of Mycobacterium bovis infection in badgers.
Bovine tuberculosis (bTB), caused by Mycobacterium bovis, represents a major animal health issue. In the United Kingdom and the Republic of Ireland, European badgers (Meles meles) have been shown to act as a reservoir of M. bovis infection, hindering the eradication of bTB in livestock. The availability of suitable diagnostic assays, particularly those that may be applied in a "trap-side" setting, would facilitate the implementation of a wider range of disease control strategies. Here we evaluate the Dual Path Platform (DPP) VetTB assay, a lateral-flow type test for detecting antibodies to M. bovis antigens (MPB83 and ESAT-6/CFP-10). Both serum and whole blood were evaluated as diagnostic samples. Additionally, two methods were evaluated for interpretation of test results (qualitative interpretation by eye and quantitative measurement using an optical reader). The antibody response to MPB83 detected by the DPP VetTB assay increased significantly following experimental M. bovis infection of badgers, whilst the response to ESAT-6/CFP-10 showed no significant change. In sera from TB-free captive and naturally M. bovis infected wild badgers the MPB83 response exhibited a sensitivity of 55 % by eye and quantitative reader (95 % CI: 40-71 and 38-71, respectively), with slightly lower specificity when read by eye (93 % compared to 98 %; 95 % CI: 85-100 and 90-100, respectively). In whole blood, the DPP VetTB assay MPB83 response exhibited a sensitivity of 65 % (95 % CI: 50-80) when interpreted by eye and 53 % (95 % CI: 36-69) using quantitative values, whilst the specificity was 94 % and 98 % respectively (95 % CI: 88-100 and 90-100). Comparison with contemporaneous diagnostic test results from putatively naturally infected and TB-free badgers demonstrated varying levels of agreement. Using sera from naturally M. bovis infected and TB-free badgers, with post mortem confirmation of disease status, the DPP VetTB assay exhibited a sensitivity of 60 % (95 % CI: 41-77) when interpreted using quantitative values (specificity 95 %; 95 % CI: 76-100), and 67 % (95 % CI: 50-84) when read by eye (specificity 95 %; 95 % CI: 86-100). Further work is required to robustly characterize the DPP VetTB assay's performance in a wider selection of samples, and in the practical and epidemiological contexts in which it may be applied.


Broadly neutralizing antibodies against the rapidly evolving porcine reproductive and respiratory syndrome virus.
Neutralizing antibodies are a critical part of the immune armory for defense against viruses, and the mechanism by which many effective vaccines work to protect against viral infections. However, infections by rapidly evolving and genetically diverse viruses are often characterized by ineffective neutralizing antibody responses. Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly genetically diverse RNA virus that causes PRRS, the most significant disease of pigs worldwide. The prevailing view of immunity to PRRSV is characterized by delayed and ineffectual production of neutralizing antibodies lacking cross-reactivity that is necessary for vaccine efficacy. Using an ELISA-based neutralizing assay developed to analyze PRRSV growth in porcine alveolar macrophages, the naturally permissive cell of PRRSV, we showed that sera from previously infected commercial sows had high levels of neutralizing activity against diverse PRRSV strains, including across distinct genotypes of PRRSV. Fifty percent cross-neutralization titers in excess of 1/1024 were observed. Neutralizing activity was dose-dependent and was maintained in the immunoglobulin fraction. Presence of high-titer, anti-PRRSV antibody activity that cross-neutralizes diverse strains of virus has prompted reevaluation of the role of neutralizing antibodies for cross-protection against PRRSV under field conditions. Understanding conditions that favor development of cross-neutralizing activity will be crucial for improved strategies to enhance cross-protection against PRRSV. More detailed studies are expected to elucidate mechanisms of neutralizing antibody production and maturation and to investigate conserved epitope targets of cross-neutralization in this rapidly evolving virus.


Genetic diversity of Dahongjun, the commercially important "Big Red Mushroom" from southern China.
In southern China, a wild ectomycorrhizal mushroom commonly called "Dahongjun" or "Big Red Mushroom" by the local residents, has been harvested, consumed, and/or exported as an exotic food for many years. Although ecologically and economically important, very little is known about this mushroom, including its diversity and population structure. In this study, we analyzed 122 samples from five local populations representing the known distribution ranges of this mushroom in southern China. We investigated the genetic diversity and geographic structure of this mushroom using sequences from four DNA fragments. Our analyses identified that this mushroom contained at least three divergent lineages: one corresponds to a recently described species Russula griseocarnosa from southern China and the remaining two likely represent two novel species. While these lineages were prominently structured geographically based on ITS sequences, evidence for ancient and/or recent gene flow was also identified within individual lineages. In addition, a local population from Ailaoshan in central Yunnan Province where 85 of our 122 specimens came from showed clear evidence of recombination. The ectomycorrhizal mushroom "Dahongjun" from southern China is a species complex with at least three divergent lineages. These lineages are largely geographically structured and there is evidence for recombination in nature. Our results indicate mature Dahongjun mushrooms with abundant basidiospores are important for the reproduction of this mushroom in nature and that individual populations of this species should be managed separately.


An alternative approach to relapse analysis: Using Monte Carlo methods and proportional rates of response.
Relapse is the recovery of a previously suppressed response. Animal models have been useful in examining the mechanisms underlying relapse (e.g., reinstatement, renewal, reacquisition, resurgence). However, there are several challenges to analyzing relapse data using traditional approaches. For example, null hypothesis significance testing is commonly used to determine whether relapse has occurred. However, this method requires several a priori assumptions about the data, as well as a large sample size for between-subjects comparisons or repeated testing for within-subjects comparisons. Monte Carlo methods may represent an improved analytic technique, because these methods require no prior assumptions, permit smaller sample sizes, and can be tailored to account for all of the data from an experiment instead of some limited set. In the present study, we conducted reanalyses of three studies of relapse (Berry, Sweeney, & Odum, ; Galizio et al., ; Odum & Shahan, ) using Monte Carlo techniques to determine if relapse occurred and if there were differences in rate of response based on relevant independent variables (such as group membership or schedule of reinforcement). These reanalyses supported the previous findings. Finally, we provide general recommendations for using Monte Carlo methods in studies of relapse.


One-year efficacy and safety of naloxegol on symptoms and quality of life related to opioid-induced constipation in patients with cancer: KYONAL study.
Naloxegol is a peripherally acting µ-opioid receptor antagonist (PAMORA) for treatment of opioid-induced constipation (OIC). The main objective was to analyse the long-term efficacy, quality of life (QOL) and safety of naloxegol in patients with cancer in a real-world study. This one-year prospective study included patients older than 18 years, with active oncological disease who were under treatment with opioids for pain control and Karnofsky≥50 and OIC with inadequate response to treatment with laxative (s). All the patients received treatment with naloxegol according to clinical criteria. The main efficacy objectives were measured by the patient assessment of constipation QOL questionnaire (PAC-QOL), the PAC symptoms (PAC-SYM), the response rate at day 15, and months 1-3-6-12, and global QOL (EuroQoL-5D-5L). A total of 126 patients (58.7% males) with a mean age of 61.5 years (95% CI 59.4 to 63.7) were included. PAC-SYM and PAC-QOL total score and all their dimensions improved from baseline (p<0.0001). At 12 months, 77.8% of the patients were responders to naloxegol treatment. Global QOL was conserved from baseline. A total of 28 adverse reactions, mainly gastrointestinal were observed in 15.1% of the patients (19/126), being 75% (21) mild, 17.9% (5) moderate and 7.1% (2) severe. Most adverse reactions (67.9%) appeared the first 15 days of treatment. The results of this first long-term and real-world-data study in patients with cancer, showed the sustained efficacy and safety of naloxegol for the treatment of OIC in this group of patients.


Optimality and identification of dynamic models in systems biology: an inverse optimal control framework.
Optimality principles have been used to explain many biological processes and systems. However, the functions being optimized are in general unknown a priori. Here we present an inverse optimal control framework for modeling dynamics in systems biology. The objective is to identify the underlying optimality principle from observed time-series data and simultaneously estimate unmeasured time-dependent inputs and time-invariant model parameters. As a special case, we also consider the problem of optimal simultaneous estimation of inputs and parameters from noisy data. After presenting a general statement of the inverse optimal control problem, and discussing special cases of interest, we outline numerical strategies which are scalable and robust. We discuss the existence, relevance and implications of identifiability issues in the above problems. We present a robust computational approach based on regularized cost functions and the use of suitable direct numerical methods based on the control-vector parameterization approach. To avoid convergence to local solutions, we make use of hybrid global-local methods. We illustrate the performance and capabilities of this approach with several challenging case studies, including simulated and real data. We pay particular attention to the computational scalability of our approach (with the objective of considering large numbers of inputs and states). We provide a software implementation of both the methods and the case studies. The code used to obtain the results reported here is available at https://zenodo.org/record/1009541. Supplementary data are available at Bioinformatics online.


BioPepDB: an integrated data platform for food-derived bioactive peptides.
Food-derived bioactive peptides play critical roles in regulating most biological processes and have considerable biological, medical and industrial importance. However, a large number of active peptides data, including sequence, function, source, commercial product information, references and other information are poorly integrated. BioPepDB is a searchable database of food-derived bioactive peptides and their related articles, including more than four thousand bioactive peptide entries. Moreover, BioPepDB provides modules of prediction and hydrolysis-simulation for discovering novel peptides. It can serve as a reference database to investigate the function of different bioactive peptides. BioPepDB is available at http://bis.zju.edu.cn/biopepdbr/ . The web page utilises Apache, PHP5 and MySQL to provide the user interface for accessing the database and predict novel peptides. The database itself is operated on a specialised server.


The effect of orally administered clodronate on bone mineral density and bone geometry in ovariectomized rats.
The effects of clodronate administered p.o. on bone mineral density (BMD), bone geometry and strength of bone were investigated in 6-month-old ovariectomized rats. Sixty Sprague-Dawley rats were randomized into four groups. Three groups were ovariectomized (OVX) and one group was sham-operated (SHAM). The OVX groups were given p.o. either clodronate (100 mg/kg/d or 500 mg/kg/d) or a vehicle. The SHAM group received the vehicle. Treatments started on the day of OVX and continued for 3 months. BMD of proximal tibial metaphysis was measured by computed tomography in vivo 1 day before OVX and 6 and 12 weeks after OVX. At the end of the study, left tibiae and femora were removed for ex vivo BMD and bone geometry measurement. A three-point bending test of the tibial shaft was carried out, and ash weights of femur and tibia were determined. OVX induced a marked decrease in total and trabecular BMD over time at the proximal tibial metaphysis. This bone loss was prevented by clodronate. Clodronate also prevented the decrease in BMD and change in bone geometry at distal and proximal femur, as well as the decrease in total ash weight of femur and tibia. OVX did not cause any marked changes in cortical BMD or bone geometry at the level of mid-diaphysis of tibia or femur over a 3-month period. Neither were there any changes between groups in bending strength in the tibial diaphysis. However, a positive correlation (n = 58, r = 0.51, P < .001) was found between bending strength and calculated density-weighted polar moment of resistance of tibial diaphysis. We conclude that clodronate administered p.o. in adult rats prevents changes due to estrogen deficiency in BMD and bone geometry.


Disparities in knowledge and use of tobacco treatment among smokers in California following healthcare reform.
The Affordable Care Act (ACA) promised to narrow smoking disparities by expanding access to healthcare and mandating comprehensive coverage for tobacco treatment starting in 2014. We examined whether two years after ACA implementation disparities in receiving clinician advice to quit and smokers' knowledge and use of treatment resources remained. We conducted telephone interviews in 2016 with a stratified random sample of self-reported smokers newly enrolled in the Kaiser Permanente Northern California's (KPNC) integrated healthcare delivery system in 2014 (N = 491; 50% female; 53% non-white; 6% Spanish language). We used Poisson regression with robust standard errors to test whether sociodemographics, insurance type, comorbidities, smoking status in 2016 (former, light/nondaily [<5 cigarettes per day], daily), and preferred language (English or Spanish) were associated with receiving clinician advice to quit and knowledge and use of tobacco treatment. We included an interaction between smoking status and language to test whether the relation between smoking status and key outcomes varied with preferred language. Overall, 80% of respondents received clinician advice to quit, 84% knew that KPNC offers cessation counseling, 54% knew that cessation pharmacotherapy is free, 54% used pharmacotherapy, and 6% used counseling. In multivariate models, Spanish-speaking light/nondaily smokers had significantly lower rates of all outcomes, while there was no association with other demographic and clinical characteristics. Following ACA implementation, most smokers newly enrolled in KPNC received clinician advice to quit and over half used pharmacotherapy, yet counseling utilization was low. Spanish-language outreach efforts and treatment services are recommended, particularly for adults who are light/nondaily smokers.


Lipid metabolism in peroxisomes: enzymology, functions and dysfunctions of the fatty acid alpha- and beta-oxidation systems in humans.
Peroxisomes are subcellular organelles present in virtually all eukaryotic cells catalysing a number of indispensable functions in cellular metabolism. The importance of peroxisomes in man is stressed by the existence of an expanding group of genetic diseases in which there is an impairment in one or more peroxisomal functions. One of the major functions of peroxisomes concerns their role in lipid metabolism, which includes: (i) fatty acid betaoxidation; (ii) ether phospholipid synthesis; (iii) fatty acid alpha-oxidation; and (iv) isoprenoid biosynthesis. In this paper, we review the current state of knowledge concerning the peroxisomal fatty acid alpha- and beta-oxidation systems with particular emphasis on the enzymes involved and the various disorders of fatty acid oxidation in peroxisomes. We also pay attention to the fact that some of the metabolites that accumulate as the result of a defect in peroxisomal alpha- and/or beta-oxidation are activators of members of the family of nuclear receptors, including peroxisome-proliferator-activated receptor alpha.


Managing gender diversity in healthcare: getting it right.
Purpose Diversity, notably gender diversity, is growing in health care, both at the level of teams and the level of organizations. This paper aims to describe the challenges for team leaders and leaders of organizations to manage this diversity. The authors believe that more could be done to help leaders master these challenges in a way that makes diverse teams and organizations more productive. Design/methodology/approach Drawing on previously published research, using gender diversity as an example, the paper first describes how diversity can both have a positive and a negative influence on team productivity. Next, it describes the challenge of gender diversity at an organizational level, using Switzerland as an example. Findings The first part of the paper espouses the causes of gender diversity, undoes some of the myths surrounding diversity and presents a model for effective management of diversity in teams. The second part looks at gender diversity at an organizational level. Drawing from sources inside and outside healthcare, the effects of the "leaking pipeline", "glass wall" and "glass ceiling" that prevent health-care organizations from leveraging the potential of female talent are discussed. Practical implications The authors propose a model developed for intercultural teamwork as a framework for leveraging gender diversity for better team productivity. Proposals are offered to health-care organizations on how they can tip the gender balance at senior levels into their favor, so as to get the maximum benefit from the available talent. Originality/value Applying the "how to" ideas and recommendations from this general review will help leaders of health-care organizations gain a better return on investment from their talent development as well as to increase the productivity of their workforce by a better use of diverse talent.


Classification of cytotoxic T-cell and natural killer cell lymphomas.
Mature or peripheral T-cell lymphomas are uncommon, accounting for only 10% to 15% of all non-Hodgkin's lymphomas. The classification of these neoplasms has been controversial. In contrast to B-cell lymphomas, cytologic features have not been useful in defining disease entities, and cytologic grade has not helped predict the clinical course. Similarly, many entities of T-cell or natural killer (NK) cell derivation do not have a specific immunophenotype. Clinical features are of major importance in defining T-cell and NK cell neoplasms, and in some cases the clinical syndrome, may be more important than the precise cell of origin. The majority of cytotoxic T-cell and NK cell lymphomas arise in extranodal sites. The expression of cytotoxic molecules in these lymphomas may predispose to apoptosis by tumor cells and normal bystander cells. Three major categories of extranodal T/NK cell tumors are recognized in the World Health Organization (WHO) classification: extranodal NK/T, nasal-type; enteropathy-type; and subcutaneous panniculitis-like. Epstein Barr virus (EBV) is closely linked to nasal NK/T-cell lymphoma, but shows geographic and racial variations in other subtypes. Tumors resembling the prototype of nasal NK/T-cell lymphoma occur in a variety of extranodal sites, and are referred to as nasal-type. Hepatosplenic T-cell lymphoma is a more systemic disease derived from functionally immature cytotoxic cells, usually gammadelta T-cell origin. Cytotoxic T-cell lymphomas of mature gammadelta T-cell origin most often arise in mucocutaneous sites, and may resemble the prototypes of extranodal T/NK cell lymphoma: nasal, enteropathy-associated, and panniculitis-like. Cytotoxic T/NK cell lymphomas occur with increased frequency in the setting of immune suppression, especially following organ transplantation. The nodal T-cell lymphoma most often exhibiting a cytotoxic immunophenotype is anaplastic large cell lymphoma (ALCL). Primary cutaneous ALCL frequently but not invariably expresses cytotoxic molecules. While the majority of extranodal neoplasms are derived from innate immune effector cells of NK cell and T-cell origin (gammadelta greater than alphabeta), most nodal cytotoxic T-cell lymphomas probably belong to the adaptive immune system. Studies of these neoplasms may assist in unraveling the diversity of their normal counterparts.


Expression of brain specific chondroitin sulfate proteoglycans, neurocan and phosphacan, in the developing and adult hippocampus of Ihara's epileptic rats.
Ihara's epileptic rats (IER) is an animal model of temporal lobe epilepsy with mycrodysgenesis, that exhibit abnormal migration of hippocampal neurons and recurrent spontaneous seizures. As an attempt to elucidate the roles of extracellular matrix molecules in the epileptogenecity and mossy fiber sprouting, immunohistochemical localization of brain specific chondroitin sulfate proteoglycans (CSPGs), neurocan and phosphacan, was examined in the hippocampus of postnatal IER and Sprague-Dawley (SD) rats using monoclonal antibodies 1G2 against neurocan and 6B4 against phosphacan. There was no difference in the expression of these two CSPGs between IER and SD rats in the 1st postnatal week. However, the expression of neurocan was poor in the hippocampus of IER in the 2nd and 3rd weeks whereas intense labeling of neurocan was present throughout the hippocampus of SD rats. Labeling of neurocan was almost absent in the hippocampus, while phosphacan was diffusely expressed in the stratum oriens and radiatum of Ammon's horn, and in the hilus and inner one-third molecular layer of the dentate gyrus at the 2nd month after birth. There was no difference in the expression of neurocan and phosphacan between IER and SD rats at the 2nd month after birth. By contrast, phosphacan was reduced in the inner molecular layer of the dentate gyrus in 8-month-old IER, while neurocan was reexpressed in the outer molecular layer and hilus in 3- and 8-month-old IER. It was suggested that the insufficient expression of neurocan may affect the development of neuronal organization in the hippocampus, and that the remodeling of extracellular matrix in the dentate gyrus may contribute to the mossy fiber sprouting into the inner molecular layer.