Long-term follow-up of pyrolytic carbon metacarpophalangeal implants.
The metacarpophalangeal joint is the most commonly involved joint when rheumatoid arthritis affects the hand. Many prosthetic implants have been designed for the replacement of this joint. Although studies of these implants have shown relief of pain, they have generally demonstrated a poor range of motion, progression of ulnar drift, and bone loss, as well as failure, fracture, and dislocation of the implant. From December 1979 to February 1987, 151 pyrolytic carbon metacarpophalangeal implants were inserted in fifty-three patients. The implants had an articulating, unconstrained design with a hemispherical head and grooved, offset stems. Forty-four patients had rheumatoid arthritis; five, posttraumatic arthritis; three, osteoarthritis; and one, systemic lupus erythematosus. Three patients (eleven implants) were lost to long-term follow-up, and twenty patients (fifty-one functioning implants) died after the implant had been in situ for an average of 7.2 years. Eighteen implants (12 percent) in eleven patients were revised. Fourteen of the eighteen implants were replaced with a silicone-elastomer or another type of implant, and the remaining four were removed and a pyrolytic carbon implant was reinserted with the addition of bone cement or bone graft, or both. Twenty-six patients (seventy-one implants) were available for long-term review at an average of 11.7 years (range, 10.1 to 16.0 years) after implantation. The implants improved the arc of motion of the fingers by an average of 13 degrees and elevated the arc by an average of 16 degrees. As a result, fingers were in a more functional, extended position. A complete set of preoperative, postoperative, and follow-up radiographs was available for fifty-three of the seventy-one implants that were followed long term. There was a high prevalence of joint stability: fifty (94 percent) of the fifty-three implants were in a reduced position postoperatively, and forty-one (82 percent) of those fifty implants were still in the postoperative reduced position at the time of long-term follow-up. Ulnar deviation averaged 20 degrees preoperatively and 19 degrees at the time of follow-up, with only the long finger having an increase in deviation. No adverse remodeling or resorption of bone was seen. Fifty (94 percent) of the fifty-three implants had evidence of osseointegration, with sclerosis around the end and shaft of the prosthetic stems. Radiolucent changes were seen adjacent to twelve implants. There was minimum-to-moderate subsidence (four millimeters or less) of thirty-four implants; most of the subsidence occurred immediately postoperatively. Survivorship analysis demonstrated an average annual failure rate of 2.1 percent and a sixteen-year survival rate of 70.3 percent. The five and ten-year survival rates were 82.3 percent (95 percent confidence interval, 74.6 to 88.2 percent) and 81.4 percent (95 percent confidence interval, 73.0 to 87.8 percent), respectively. None of the revised implants had any visible changes of wear or deformity of the surfaces or stems. Four instances of chronic inflammatory tissue and three instances of proliferative synovitis were noted histologically. Focal pigment deposits were seen in three fingers, one of which had removal of the implant two months after a fracture. No evidence of intracellular particles or particulate synovitis was found. The results of this study demonstrate that pyrolytic carbon is a biologically and biomechanically compatible, wear-resistant, and durable material for arthroplasty of the metacarpophalangeal joint.


Effect of various degrees of systemic arterial hypertension on acute canine myocrdial ischemia.
There is continuing uncertainty about the effects of various degrees of systemic arterial hypertension on myocardial ischemia. In 46 open-chest anesthetized dogs, intramural carbon dioxide tension (PmCO2) was measured directly with a mass spectrometer during repetitive 10-min coronary artery occlusions separated by 45-min periods of reflow. During each occlusion, transmural regional myocardial blood flow (RMBF) in the ischemic area was quantitated with the injection of radioactive microspheres (7-10 micrometers diam). In all dogs the increase in PmCO2 from before to 10 min after the first occlusion (delta PmCO2) exceeded that during subsequent occlusions. In those dogs in which systemic arterial hypertension was not produced (controls), delta PmCO2 during the third occlusion was similar to that during the second occlusion. When phenylephrine was administered during the third occlusion to increase systemic arterial pressure mildly (diastolic pressure 95-115 mmHg), RMBF to the ischemic myocardium was unchanged, and the severity of myocardial ischemia was reduced, as reflected by a fall in delta PmCO2. When diastolic pressure was elevated moderately (116-140 mmHg), RMBF was augmented, but the extent of myocardial ischemia was neither diminished nor worsened. In contrast, when diastolic pressure was increased markedly (greater than 140 mmHg), myocardial ischemic injury was intensified (as reflected by an increase in delta PmCO2) even though RMBF rose significantly. Thus, in the dog with acute coronary artery occlusion, an increase of systemic arterial pressure exerts an influence on the severity of myocardial ischemic injury that is related directly to the magnitude of systemic arterial hypertension: a mild increase of pressure reduces ischemic injury, a moderate increase exerts no consistent effect on ischemia, and a marked increase worsens ischemic injury.


Synthesis of 4-C-alkyl inositol 1,4,5-trisphosphates and 1,3,4,5-tetrakisphosphates.
The preparation of 2,3,6-O-tribenzyl- and 2,6-O-dibenzyl-myo-inositols with beta-primary, secondary, and tertiary 4-C-alkyl or aryl groups is reported. Five of these novel polyols are elaborated to 4-C-alkyl Ins(1,4,5)P(3) and Ins(1,3,4,5)P(4) analogues. Regio- and stereoselective introduction of 4-C-alkyl or aryl substituents proceeded via a 4-exo-methylene oxide. Subsequent regioselective reduction of an orthobenzoate provided a divergent method to access both InsP(3) and InsP(4) precursors. Previously unreported phosphorylation of the tertiary hydroxyl and global deprotection afforded novel analogues that retain their full complement of polar and charged binding features.


Differentiating Plasmodium falciparum alleles by transforming Cartesian X,Y data to polar coordinates.
Diagnosis of infectious diseases now benefits from advancing technology to perform multiplex analysis of a growing number of variables. These advances enable simultaneous surveillance of markers characterizing species and strain complexity, mutations associated with drug susceptibility, and antigen-based polymorphisms in relation to evaluation of vaccine effectiveness. We have recently developed assays detecting single nucleotide polymorphisms (SNPs) in the P. falciparum genome that take advantage of post-PCR ligation detection reaction and fluorescent microsphere labeling strategies. Data from these assays produce a spectrum of outcomes showing that infections result from single to multiple strains. Traditional methods for distinguishing true positive signal from background can cause false positive diagnoses leading to incorrect interpretation of outcomes associated with disease treatment. Following analysis of Plasmodium falciparum dihydrofolate reductase SNPs associated with resistance to a commonly used antimalarial drug, Fansidar (Sulfadoxine/pyrimethamine), and presumably neutral SNPs for parasite strain differentiation, we first evaluated our data after setting a background signal based on the mean plus three standard deviations for known negative control samples. Our analysis of single allelic controls suggested that background for the absent allele increased as the concentration of the target allele increased. To address this problem, we introduced a simple change of variables from customary (X,Y) (Cartesian) coordinates to planar polar coordinates (X = rcos(theta), Y = rsin(theta)). Classification of multidimensional fluorescence signals based on histograms of angular and radial data distributions proved more effective than classification based on Cartesian thresholds. Comparison with known diallelic dilution controls suggests that histogram-based classification is effective for major:minor allele concentration ratios as high as 10:1. We have observed that the diallelic SNP data resulting from analysis of P. falciparum mutations is more accurately diagnosed when a simple polar transform of the (X,Y) data into (r,theta) is used. The development of high through-put methods for genotyping P. falciparum SNPs and the refinement of analytical approaches for evaluating these molecular diagnostic results significantly advance the evaluation of parasite population diversity and antimalarial drug resistance.


Correlates of delayed sexual intercourse and condom use among adolescents in Uganda: a cross-sectional study.
Comprehensive sex education, including the promotion of consistent condom use, is still an important intervention strategy in tackling unplanned pregnancies, HIV/AIDS and sexually transmitted infections (STIs) among Ugandan adolescents. This study examines predictors of the intention to use a condom and the intention to delay sexual intercourse among secondary school students (aged 12-20) in Uganda. A school-based sample was drawn from 48 secondary schools throughout Uganda. Participants (N = 1978) completed a survey in English measuring beliefs regarding pregnancy, STIs and HIV and AIDS, attitudes, social norms and self-efficacy towards condom use and abstinence/delay, intention to use a condom and intention to delay sexual intercourse. As secondary sexual abstinence is one of the recommended ways for preventing HIV, STIs and unplanned pregnancies among the sexually experienced, participants with and without previous sexual experience were compared. For adolescents without sexual experience (virgins), self-efficacy, perceived social norms and attitude towards condom use predicted the intention to use condoms. Among those with sexual experience (non-virgins), only perceived social norm was a significant predictor. The intention to delay sexual intercourse was, however, predicted similarly for both groups, with attitudes, perceived social norm and self-efficacy being significant predictors. This study has established relevant predictors of intentions of safe sex among young Ugandans and has shown that the intention to use condoms is motivated by different factors depending on previous sexual experience. A segmented approach to intervention development and implementation is thus recommended.


Preferential interaction coefficients of proteins in aqueous arginine solutions and their molecular origins.
Preferential interaction coefficients provide a thermodynamic measure to quantify the interactions between cosolutes and a protein. Preferential interactions of cosolutes can be measured experimentally using dialysis/densimetry and vapor pressure osmometry (VPO) techniques. The cosolute arginine is a widely used aggregation suppressor with a seemingly unique behavior. Its role in protein aggregation has been studied extensively, although a complete mechanistic understanding of its behavior is lacking. Moreover, due to experimental limitations, experimental preferential interaction data for arginine has only been reported at low concentrations. Schneider and Trout ( J. Phys. Chem. B 2009 , 113 , 7 ) have reported experimental preferential interaction data for argHCl (up to 0.7 m), and their study raised several interesting questions about the preferential interaction of arginine with proteins. Arginine is attracted to proteins at low concentrations but it was highly excluded at high concentrations. Furthermore, the preferential interaction coefficient values were found to vary as a square of the concentration, which is different from commonly observed linear relationship for other cosolutes like urea, glycerol, guanidinium hydrochloride, etc. In this study, preferential interaction coefficients of argHCl have been estimated computationally for two proteins (lysozyme and α-chymotripsinogen A) for a large concentration range (up to 2.8 m). On the basis of these results, the molecular level interactions responsible for the nonlinear exclusion of arginine from the protein surface are identified.


Quantifying environmental limiting factors on tree cover using geospatial data.
Environmental limiting factors (ELFs) are the thresholds that determine the maximum or minimum biological response for a given suite of environmental conditions. We asked the following questions: 1) Can we detect ELFs on percent tree cover across the eastern slopes of the Lake Tahoe Basin, NV? 2) How are the ELFs distributed spatially? 3) To what extent are unmeasured environmental factors limiting tree cover? ELFs are difficult to quantify as they require significant sample sizes. We addressed this by using geospatial data over a relatively large spatial extent, where the wall-to-wall sampling ensures the inclusion of rare data points which define the minimum or maximum response to environmental factors. We tested mean temperature, minimum temperature, potential evapotranspiration (PET) and PET minus precipitation (PET-P) as potential limiting factors on percent tree cover. We found that the study area showed system-wide limitations on tree cover, and each of the factors showed evidence of being limiting on tree cover. However, only 1.2% of the total area appeared to be limited by the four (4) environmental factors, suggesting other unmeasured factors are limiting much of the tree cover in the study area. Where sites were near their theoretical maximum, non-forest sites (tree cover < 25%) were primarily limited by cold mean temperatures, open-canopy forest sites (tree cover between 25% and 60%) were primarily limited by evaporative demand, and closed-canopy forests were not limited by any particular environmental factor. The detection of ELFs is necessary in order to fully understand the width of limitations that species experience within their geographic range.


TIGAR induces p53-mediated cell-cycle arrest by regulation of RB-E2F1 complex.
p53 induces cell-cycle arrest and apoptosis in cancer cells and negatively regulates glycolysis via TIGAR. Glycolysis is crucial for cancer progression although TIGAR provides protection from reactive oxygen species and apoptosis. The relation between TIGAR-mediated inhibition of glycolysis and p53 tumour-suppressor activity is unknown. RT-PCR, western blot, luciferase and chromatin immunoprecipitation assays were used to study TIGAR gene regulation. Co-IPP was used to determine the role of TIGAR protein in regulating the protein-protein interaction between retinoblastoma (RB) and E2F1. MCF-7 tumour xenografts were utilised to study the role of TIGAR in tumour regression. Our study shows that TIGAR promotes p21-independent, p53-mediated G1-phase arrest in cancer cells. p53 activates the TIGAR promoter only in cells exposed to repairable doses of stress. TIGAR regulates the expression of genes involved in cell-cycle progression; suppresses synthesis of CDK-2, CDK-4, CDK-6, Cyclin D, Cyclin E and promotes de-phosphorylation of RB protein. RB de-phosphorylation stabilises the complex between RB and E2F1 thus inhibiting the entry of cell cycle from G1 phase to S phase. TIGAR mediates de-phosphorylation of RB and stabilisation of RB-E2F1 complex thus delaying the entry of cells in S phase of the cell cycle. Thus, TIGAR inhibits proliferation of cancer cells and increases drug-mediated tumour regression by promoting p53-mediated cell-cycle arrest.


Cardiorespiratory fitness, cardiovascular workload and risk factors among cleaners; a cluster randomized worksite intervention.
Prevalence of cardiovascular risk factors is unevenly distributed among occupational groups. The working environment, as well as lifestyle and socioeconomic status contribute to the disparity and variation in prevalence of these risk factors. High physical work demands have been shown to increase the risk for cardiovascular disease and mortality, contrary to leisure time physical activity. High physical work demands in combination with a low cardiorespiratory fitness infer a high relative workload and an excessive risk for cardiovascular mortality. Therefore, the aim of this study is to examine whether a worksite aerobic exercise intervention will reduce the relative workload and cardiovascular risk factors by an increased cardiorespiratory fitness. A cluster-randomized controlled trial is performed to evaluate the effect of the worksite aerobic exercise intervention on cardiorespiratory fitness and cardiovascular risk factors among cleaners. Cleaners are eligible if they are employed ≥ 20 hours/week, at one of the enrolled companies. In the randomization, strata are formed according to the manager the participant reports to. The clusters will be balanced on the following criteria: Geographical work location, gender, age and seniority. Cleaners are randomized to either I) a reference group, receiving lectures concerning healthy living, or II) an intervention group, performing worksite aerobic exercise "60 min per week". Data collection will be conducted at baseline, four months and 12 months after baseline, at the worksite during working hours. The data collection will consist of a questionnaire-based interview, physiological testing of health and capacity-related measures, and objective diurnal measures of heart rate, physical activity and blood pressure. Primary outcome is cardiorespiratory fitness. Information is lacking about whether an improved cardiorespiratory fitness will affect the cardiovascular health, and additionally decrease the objectively measured relative workload, in a population with high physical work demands. Previous intervention studies have lacked robust objective measurements of the relative workload and physical work demands. This study will monitor the relative workload and general physical activity before, during after the intervention, and contribute to the understanding of the previously observed opposing effects on cardiovascular health and mortality from occupational and leisure time physical activity. The study is registered as ISRCTN86682076.


High-throughput sequencing of microRNA transcriptome and expression assay in the sturgeon, Acipenser schrenckii.
Sturgeons are considered as living fossils and have very high evolutionary, economical and conservation values. The multiploidy of sturgeon that has been caused by chromosome duplication may lead to the emergence of new microRNAs (miRNAs) involved in the ploidy and physiological processes. In the present study, we performed the first sturgeon miRNAs analysis by RNA-seq high-throughput sequencing combined with expression assay of microarray and real-time PCR, and aimed to discover the sturgeon-specific miRNAs, confirm the expressed pattern of miRNAs and illustrate the potential role of miRNAs-targets on sturgeon biological processes. A total of 103 miRNAs were identified, including 58 miRNAs with strongly detected signals (signal >500 and P≤0.01), which were detected by microarray. Real-time PCR assay supported the expression pattern obtained by microarray. Moreover, co-expression of 21 miRNAs in all five tissues and tissue-specific expression of 16 miRNAs implied the crucial and particular function of them in sturgeon physiological processes. Target gene prediction, especially the enriched functional gene groups (369 GO terms) and pathways (37 KEGG) regulated by 58 miRNAs (P<0.05), illustrated the interaction of miRNAs and putative mRNAs, and also the potential mechanism involved in these biological processes. Our new findings of sturgeon miRNAs expand the public database of transcriptome information for this species, contribute to our understanding of sturgeon biology, and also provide invaluable data that may be applied in sturgeon breeding.


Neurophysiological and computational principles of cortical rhythms in cognition.
Synchronous rhythms represent a core mechanism for sculpting temporal coordination of neural activity in the brain-wide network. This review focuses on oscillations in the cerebral cortex that occur during cognition, in alert behaving conditions. Over the last two decades, experimental and modeling work has made great strides in elucidating the detailed cellular and circuit basis of these rhythms, particularly gamma and theta rhythms. The underlying physiological mechanisms are diverse (ranging from resonance and pacemaker properties of single cells to multiple scenarios for population synchronization and wave propagation), but also exhibit unifying principles. A major conceptual advance was the realization that synaptic inhibition plays a fundamental role in rhythmogenesis, either in an interneuronal network or in a reciprocal excitatory-inhibitory loop. Computational functions of synchronous oscillations in cognition are still a matter of debate among systems neuroscientists, in part because the notion of regular oscillation seems to contradict the common observation that spiking discharges of individual neurons in the cortex are highly stochastic and far from being clocklike. However, recent findings have led to a framework that goes beyond the conventional theory of coupled oscillators and reconciles the apparent dichotomy between irregular single neuron activity and field potential oscillations. From this perspective, a plethora of studies will be reviewed on the involvement of long-distance neuronal coherence in cognitive functions such as multisensory integration, working memory, and selective attention. Finally, implications of abnormal neural synchronization are discussed as they relate to mental disorders like schizophrenia and autism.


Role of receptor reserve in the inhibition of alpha-1 adrenoceptor-mediated pressor responses by calcium antagonists in the pithed rat.
The effect of the calcium channel antagonists nifedipine and FR 34235 on the vasopressor response to alpha-1 adrenoceptor stimulation in the pithed normotensive rat was investigated. The maximal pressor response elicited by the full alpha-1 adrenoceptor agonist SK&F l-89748 was slightly but significantly reduced by 1-mg/kg doses of nifedipine (21 +/- 2%) and FR 34235 (34 +/- 4%). In comparison, the maximal pressor response to alpha-1 adrenoceptor stimulation by the partial alpha-1 agonist SK&F 88444 was markedly inhibited by nifedipine (51 +/- 1%) and FR 34235 (65 +/- 3%). Partial inactivation of the postsynaptic alpha-1 adrenoceptors with phenoxybenzamine (0.1 mg/kg) resulted in a maximal increase in diastolic pressure to alpha-1 adrenoceptor activation by SK&F l-89748 less than that induced by SK&F 88444. After phenoxybenzamine treatment, nifedipine and FR 34235 produced even greater reductions in the maximal vasopressor response to alpha-1 adrenoceptor stimulation by SK&F l-89748 (77 +/- 8 and 85 +/- 1%, respectively). Moreover, an inverse linear correlation (r = 1.00) was observed between the sensitivity of the maximal vasopressor response to nifedipine and FR 34235 and the magnitude of the maximal pressor response. The data suggest that the sensitivity of the alpha-1 adrenoceptor-mediated pressor response to inhibition by calcium antagonists in the pithed rat is inversely related to the magnitude of the pressor response, and they are consistent with the notion that the presence of "spare" alpha-1 adrenoceptors may determine the sensitivity of the pressor response to calcium antagonists.


Studies on infection and immunity in experimental typhoid fever. I. Typhoid fever in chimpanzees orally infected with Salmonella typhosa.
A disease resembling human typhoid fever has been induced by feeding live cultures of Salmonella typhosa to young chimpanzees, thus confirming the classical reports of Grünbaum and of Metchnikoff and Besredka. Detailed clinical observations, results of stool and blood cultures, and serological studies have confirmed the impression that the disease produced in chimpanzees closely resembles the mild form of human typhoid fever frequently seen in childhood. Gross and histologic examination of intestines, mesenteric lymph nodes, liver, spleen, and other organs of orally infected chimpanzees has demonstrated that the pathological findings are essentially indistinguishable from those seen in mild typhoid fever in man. The clinical spectrum of disease seen in chimpanzees ranged from moderately severe illness, through transitory illness, to afebrile infection with or without bacteriemia (but invariably with an antibody response), occasionally leading to the development of persisting biliary infection and the carrier state. Thus the range of illness observed in chimpanzees resembled that seen in man, except that the severe and complicated forms of typhoid fever were not observed in the chimpanzee. A reason for this difference is proposed and discussed. In contrast to the limitations imposed upon the interpretation of human epidemiologic observations, it has been possible to demonstrate in the chimpanzee that clinical variation in disease pattern from animal to animal may occur despite the administration of the same dose of the same bacterial strain simultaneously to an entire group of animals under study; in other words, variation in clinical pattern is dependent on inherent, non-specific host factors as well as on dose, strain or preceding state of immunity. Variation in dose and in challenge strain of S. typhosa employed also appeared to have an effect upon the likelihood of producing febrile as against afebrile infection in chimpanzees. The dose required to produce clinical disease, even with the more virulent strain, was excessively large compared to what is believed to be the dose required to produce illness in man; the limitations of this assumption, and suggested explanations for the findings, are discussed. The production of the spectrum of typhoid fever in the chimpanzee has made possible the study of basic problems in this disease which are not amenable to definitive study through the use of prevailing laboratory techniques.


Lyme disease during pregnancy.
Lyme disease is an increasingly recognized tick-borne illness caused by a spirochete, Borrelia burgdorferi. Because the etiologic agent of Lyme disease is a spirochete, there has been concern about the effect of maternal Lyme disease on pregnancy outcome. We reviewed cases of Lyme disease in pregnant women who were identified before knowledge of the pregnancy outcomes. Nineteen cases were identified with onset between 1976 and 1984. Eight of the women were affected during the first trimester, seven during the second trimester, and two during the third trimester; in two, the trimester of onset was unknown. Thirteen received appropriate antibiotic therapy for Lyme disease. Of the 19 pregnancies, five had adverse outcomes, including syndactyly, cortical blindness, intrauterine fetal death, prematurity, and rash in the newborn. Adverse outcomes occurred in cases with infection during each of the trimesters. Although B burgdorferi could not be implicated directly in any of the adverse outcomes, the frequency of such outcomes warrants further surveillance and studies of pregnant women with Lyme disease.


Electronic and Mechanical Properties of Graphene-Germanium Interfaces Grown by Chemical Vapor Deposition.
Epitaxially oriented wafer-scale graphene grown directly on semiconducting Ge substrates is of high interest for both fundamental science and electronic device applications. To date, however, this material system remains relatively unexplored structurally and electronically, particularly at the atomic scale. To further understand the nature of the interface between graphene and Ge, we utilize ultrahigh vacuum scanning tunneling microscopy (STM) and scanning tunneling spectroscopy (STS) along with Raman and X-ray photoelectron spectroscopy to probe interfacial atomic structure and chemistry. STS reveals significant differences in electronic interactions between graphene and Ge(110)/Ge(111), which is consistent with a model of stronger interaction on Ge(110) leading to epitaxial growth. Raman spectra indicate that the graphene is considerably strained after growth, with more point-to-point variation on Ge(111). Furthermore, this native strain influences the atomic structure of the interface by inducing metastable and previously unobserved Ge surface reconstructions following annealing. These nonequilibrium reconstructions cover >90% of the surface and, in turn, modify both the electronic and mechanical properties of the graphene overlayer. Finally, graphene on Ge(001) represents the extreme strain case, where graphene drives the reorganization of the Ge surface into [107] facets. From this work, it is clear that the interaction between graphene and the underlying Ge is not only dependent on the substrate crystallographic orientation, but is also tunable and strongly related to the atomic reconfiguration of the graphene-Ge interface.


Auditory hallucinations associated with migraine: Case series and literature review.
The objective of this review is to describe auditory hallucinations (paracusias) associated with migraine attacks to yield insights into their clinical significance and pathogenesis. Isolated observations have documented rare associations of migraine with auditory hallucinations. Unlike visual, somatosensory, language, motor, and brainstem symptoms, paracusias with acute headache attacks are not a recognized aura symptom by the International Headache Society, and no systematic review has addressed this association. We retrospectively studied patients experiencing paracusias associated with migraine at our center and in the literature. We encountered 12 patients (our center = 5, literature = 7), 58% were female, and 75% had typical migraine aura. Hallucinations most commonly featured voices (58%), 75% experienced them during headache, and the duration was most often <1 hour (67%). No patients described visual aura evolving to paracusias. Most patients (50%) had either a current or previous psychiatric disorder, most commonly depression (67%). The course of headache and paracusias were universally congruent, including improvement with headache prophylaxis (58%). Paracusias uncommonly co-occur with migraine and usually feature human voices. Their timing and high prevalence in patients with depression may suggest that paracusias are not necessarily a form of migraine aura, though could be a migraine trait symptom. Alternative mechanisms include perfusion changes in primary auditory cortex, serotonin-related ictal perceptual changes, or a release phenomenon in the setting of phonophobia with avoidance of a noisy environment.


A simple cage-autonomous method for the maintenance of the barrier status of germ-free mice during experimentation.
The use of germ-free (GF) isolators for microbiome-related research is exponentially increasing, yet limited by its cost, isolator size and potential for trans-contamination. As such, current isolator technology is highly limiting to researchers engaged in short period experiments involving multiple mouse strains and employing a variety of mono-inoculated microorganisms. In this study, we evaluate the use of positive pressure Isocages as a solution for short period studies (days to 2-3 weeks) of experimentation with GF mice at multiple simultaneous conditions. We demonstrate that this new Isocage technology is cost-effective and room-sparing, and enables maintenance of multiple simultaneous groups of GF mice. Using this technology, transferring GF mice from isolators to Isocage racks for experimentation, where they are kept under fully germ-free conditions, enables parallel inoculation with different bacterial strains and simultaneous experimentation with multiple research conditions. Altogether, the new GF Isocage technology enables the expansion of GF capabilities in a safe and cost-effective manner that can facilitate the growth, elaboration and flexibility of microbiome research.


A proline-rich motif on VGLUT1 reduces synaptic vesicle super-pool and spontaneous release frequency.
Glutamate secretion at excitatory synapses is tightly regulated to allow for the precise tuning of synaptic strength. Vesicular Glutamate Transporters (VGLUT) accumulate glutamate into synaptic vesicles (SV) and thereby regulate quantal size. Further, the number of release sites and the release probability of SVs maybe regulated by the organization of active-zone proteins and SV clusters. In the present work, we uncover a mechanism mediating an increased SV clustering through the interaction of VGLUT1 second proline-rich domain, endophilinA1 and intersectin1. This strengthening of SV clusters results in a combined reduction of axonal SV super-pool size and miniature excitatory events frequency. Our findings support a model in which clustered vesicles are held together through multiple weak interactions between Src homology three and proline-rich domains of synaptic proteins. In mammals, VGLUT1 gained a proline-rich sequence that recruits endophilinA1 and turns the transporter into a regulator of SV organization and spontaneous release.


Identifying Aspiration Among Infants in Neonatal Intensive Care Units Through Occupational Therapy Feeding Evaluations.
When a neonate's sucking, swallowing, and breathing are disorganized, oropharyngeal aspiration often occurs and results in illness, developmental problems, and even death. Occupational therapists who work in the neonatal intensive care unit (NICU) need to identify neonates who are at risk for aspirating so they can provide appropriate treatment. To ascertain whether client factors and performance skills of infants ages 0-6 mo during occupational therapy feeding evaluations are related to results of videofluoroscopic swallowing studies (VFSSs). Retrospective chart reviews. 187-bed NICU in a nonprofit teaching hospital. A purposive sample of 334 infants ages 0-6 mo, ≥33 wk gestational age at birth, admitted to a Level II, III, or IV NICU as defined by the American Academy of Pediatrics. Neonates were administered a feeding evaluation by an occupational therapist and a VFSS by a speech-language pathologist, which yielded information about client factors and performance skills. Signs and symptoms of aspiration on the evaluations were significantly associated with VFSS results. Of 310 patients, 79 had silent aspiration. Of 55 infants who demonstrated no aspiration symptoms during the feeding evaluation, 45% demonstrated aspiration symptoms on the VFSS, and 55% aspirated on the VFSS but demonstrated no symptoms of aspiration. Aspiration among infants occurs inconsistently and depends on client factors, contexts, and environments. Occupational therapists are encouraged to assess an infant's feeding over several sessions to obtain a more accurate picture of the infant's feeding status. This study provides information that helps occupational therapists identify infants at risk for aspiration and make optimal recommendations regarding safe feeding practices and appropriate referrals for a VFSS. Making appropriate referrals for VFSS is also important in preventing unnecessary exposure to radiation for preterm infants.


Insights into the activation mechanism of class I HDAC complexes by inositol phosphates.
Histone deacetylases (HDACs) 1, 2 and 3 form the catalytic subunit of several large transcriptional repression complexes. Unexpectedly, the enzymatic activity of HDACs in these complexes has been shown to be regulated by inositol phosphates, which bind in a pocket sandwiched between the HDAC and co-repressor proteins. However, the actual mechanism of activation remains poorly understood. Here we have elucidated the stereochemical requirements for binding and activation by inositol phosphates, demonstrating that activation requires three adjacent phosphate groups and that other positions on the inositol ring can tolerate bulky substituents. We also demonstrate that there is allosteric communication between the inositol-binding site and the active site. The crystal structure of the HDAC1:MTA1 complex bound to a novel peptide-based inhibitor and to inositol hexaphosphate suggests a molecular basis of substrate recognition, and an entropically driven allosteric mechanism of activation.


Hubris, humility and humanity: expanding evidence approaches for improving and sustaining community health programmes.
Community-based approaches are a critical foundation for many health outcomes, including reproductive, maternal, newborn and child health (RMNCH). Evidence is a vital part of strengthening that foundation, but largely focuses on the technical content of what must be done, rather than on how disparate community actors continuously interpret, implement and adapt interventions in dynamic and varied community health systems. We argue that efforts to strengthen evidence for community programmes must guard against the hubris of relying on a single approach or hierarchy of evidence for the range of research questions that arise when sustaining community programmes at scale. Moving forward we need a broader evidence agenda that better addresses the implementation realities influencing the scale and sustainability of community programmes and the partnerships underpinning them if future gains in community RMNCH are to be realised. This will require humility in understanding communities as social systems, the complexity of the interventions they engage with and the heterogeneity of evidence needs that address the implementation challenges faced. It also entails building common ground across epistemological word views to strengthen the robustness of implementation research by improving the use of conceptual frameworks, addressing uncertainty and fostering collaboration. Given the complexity of scaling up and sustaining community RMNCH, ensuring that evidence translates into action will require the ongoing brokering of relationships to support the human creativity, scepticism and scaffolding that together build layers of evidence, critical thinking and collaborative learning to effect change.


Temporal dynamics of attention during encoding versus maintenance of working memory: complementary views from event-related potentials and alpha-band oscillations.
Working memory (WM) is strongly influenced by attention. In visual WM tasks, recall performance can be improved by an attention-guiding cue presented before encoding (precue) or during maintenance (retrocue). Although precues and retrocues recruit a similar frontoparietal control network, the two are likely to exhibit some processing differences, because precues invite anticipation of upcoming information whereas retrocues may guide prioritization, protection, and selection of information already in mind. Here we explored the behavioral and electrophysiological differences between precueing and retrocueing in a new visual WM task designed to permit a direct comparison between cueing conditions. We found marked differences in ERP profiles between the precue and retrocue conditions. In line with precues primarily generating an anticipatory shift of attention toward the location of an upcoming item, we found a robust lateralization in late cue-evoked potentials associated with target anticipation. Retrocues elicited a different pattern of ERPs that was compatible with an early selection mechanism, but not with stimulus anticipation. In contrast to the distinct ERP patterns, alpha-band (8-14 Hz) lateralization was indistinguishable between cue types (reflecting, in both conditions, the location of the cued item). We speculate that, whereas alpha-band lateralization after a precue is likely to enable anticipatory attention, lateralization after a retrocue may instead enable the controlled spatiotopic access to recently encoded visual information.


Drinking Water Supply in the Region of Antofagasta (Chile): A Challenge between Past, Present and Future.
Since the mid-nineteen century, when the first mining companies were established in the region of Antofagasta to extract saltpeter, mining managers and civil authorities have always had to face a number of problems to secure a water supply sufficient for the development of industrial activities and society. The unique features of the region, namely the scarcity of rainfall, the high concentration of arsenic in freshwaters and the increasing pressure of the mining sector, have made the supply of drinking water for local communities a challenge. In the 1950s, the town of Antofagasta experienced a serious drinking water crisis. The 300 km long aqueduct starting from the Toconce catchment, opened in 1958, temporarily ended this shortage of drinking water but created an even more dramatic problem. The concentration of arsenic in the water consumed by the population had grown by approx. ten times, reaching the value of 0.860 mg/L and seriously affecting people's health. The water treatment plants (WTPs) which were installed starting from the 1970s in the region (namely the Old and New Salar del Carmen in Antofagasta and Cerro Topater in Calama, plus the two recent desalination plants in Antofagasta and Tocopilla), have ensured, since 2014, that the drinking water coverage in the urban areas was practically universal (>99.9%). However, the rural areas have continued to experience significant shortcomings regarding their capacity to ensure the quality and continuity of the water supply service in the long run. Presently, approx. 42% of the rural population of the region of Antofagasta does not have a formal supply of drinking water. The recent amendments to the Chilean Water Code (March 2022) and the interventions carried out in the framework of the Agua Potable Rural (APR) program were intended to reduce the socio-ecological inequalities due to the lack of drinking water in the semi-concentrated and isolated rural population.


Are human mating preferences with respect to height reflected in actual pairings?
Pair formation, acquiring a mate to form a reproductive unit, is a complex process. Mating preferences are a step in this process. However, due to constraining factors such as availability of mates, rival competition, and mutual mate choice, preferred characteristics may not be realised in the actual partner. People value height in their partner and we investigated to what extent preferences for height are realised in actual couples. We used data from the Millennium Cohort Study (UK) and compared the distribution of height difference in actual couples to simulations of random mating to test how established mate preferences map on to actual mating patterns. In line with mate preferences, we found evidence for: (i) assortative mating (r = .18), (ii) the male-taller norm, and, for the first time, (iii) for the male-not-too-tall norm. Couples where the male partner was shorter, or over 25 cm taller than the female partner, occurred at lower frequency in actual couples than expected by chance, but the magnitude of these effects was modest. We also investigated another preference rule, namely that short women (and tall men) prefer large height differences with their partner, whereas tall women (and short men) prefer small height differences. These patterns were also observed in our population, although the strengths of these associations were weaker than previously reported strength of preferences. We conclude that while preferences for partner height generally translate into actual pairing, they do so only modestly.


Improved bone biomechanical properties in rats after oral xylitol administration.
The effects of 5, 10, and 20% dietary xylitol supplementations on the biomechanical properties, histological architecture, and the contents of collagen, pyridinoline, and deoxypyridinoline in long bones of rats were studied. Tibiae were used for the three-point bending test, and femurs were used for the torsion and loading test of the femoral neck. The 10 and 20% oral xylitol administrations caused a significant increase of tibial stress, femoral shear stress, and stress of the femoral neck as compared with the controls. Parallel, but not significant, effects were also seen in the 5% xylitol supplementation group. No significant differences in strain or Young's modulus of the tibiae were detected between the groups. An increased shear modulus of elasticity in femurs was detected in the 20% supplementation group as compared with the controls. The histomorphometrical data for the secondary spongiosa of the proximal tibia revealed that trabecular bone volume was significantly greater in all dietary xylitol supplementation groups as compared with the controls. The bone volume increased along with increasing xylitol content. No significant differences between the groups were detected concerning the amount of collagen per dry weight of organic matrix, the concentrations of pyridinoline or deoxypyridinoline in collagen, or the ratio of these crosslinks. This suggests no xylitol-dependent selective changes in these structures of bone collagen. In conclusion, dietary xylitol supplementation in rats improves the biomechanical properties of bone and increases the trabecular bone volume dose dependently.


Validation of an acoustic gastrointestinal surveillance biosensor for postoperative ileus.
Postoperative ileus (POI) can worsen outcomes, increase cost, and prolong hospitalization. An objective marker could help identify POI patients who should not be prematurely fed. We developed a disposable, non-invasive acoustic gastro-intestinal surveillance (AGIS) biosensor. We tested whether AGIS can distinguish healthy controls from patients recovering from abdominal surgery. AGIS is a disposable plastic device embedded with a microphone that adheres to the abdominal wall and connects to a computer that measures acoustic event rates. We compared intestinal rates of healthy subjects using AGIS for 60 min after a standardized meal to recordings of two postoperative groups: (1) patients tolerating standardized feeding and (2) POI patients. We compared intestinal rates among groups using ANOVA and t tests. There were 8 healthy controls, 7 patients tolerating feeding, and 25 with POI; mean intestinal rates were 0.14, 0.03, and 0.016 events per second, respectively (ANOVA p < 0.001). AGIS separated patients from controls with 100 % sensitivity and 97 % specificity. Among patients, rates were higher in fed versus POI subjects (p = 0.017). Non-invasive, abdominal acoustic monitoring distinguishes POI from non-POI subjects. Future research will test whether AGIS can identify patients at risk for development of POI and assist with postoperative feeding decisions.


From Markovian to pairwise epidemic models and the performance of moment closure approximations.
Many if not all models of disease transmission on networks can be linked to the exact state-based Markovian formulation. However the large number of equations for any system of realistic size limits their applicability to small populations. As a result, most modelling work relies on simulation and pairwise models. In this paper, for a simple SIS dynamics on an arbitrary network, we formalise the link between a well known pairwise model and the exact Markovian formulation. This involves the rigorous derivation of the exact ODE model at the level of pairs in terms of the expected number of pairs and triples. The exact system is then closed using two different closures, one well established and one that has been recently proposed. A new interpretation of both closures is presented, which explains several of their previously observed properties. The closed dynamical systems are solved numerically and the results are compared to output from individual-based stochastic simulations. This is done for a range of networks with the same average degree and clustering coefficient but generated using different algorithms. It is shown that the ability of the pairwise system to accurately model an epidemic is fundamentally dependent on the underlying large-scale network structure. We show that the existing pairwise models are a good fit for certain types of network but have to be used with caution as higher-order network structures may compromise their effectiveness.


Genome-wide chromatin immunoprecipitation-sequencing in Plasmodium.
Chromatin immunoprecipitation (ChIP) studies have been used extensively in recent years to study the functional role of histone marks, variant histones, and other chromatin factors in gene expression in the human malaria parasite, Plasmodium falciparum. In this chapter, we present a ChIP-sequencing protocol optimized for blood-stage forms of this parasite. The processing of the immunoprecipitated DNA prior to high-throughput sequencing is performed in a way to minimize amplification biases due to the high genomic AT-content of the parasite.


Does physiological response to disease incur cost to reproductive ecology in a sexually dichromatic amphibian species?
It is well known that the disease chytridiomycosis, caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd) has contributed to amphibian declines worldwide. The impact of Bd varies, with some species being more susceptible to infection than others. Recent evidence has shown that Bd can have sub-lethal effects, whereby increases in stress hormones have been associated with infection. Could this increased stress response, which is a physiological adaptation that provides an increased resilience against Bd infection, potentially be a trade-off with important life-history traits such as reproduction? We studied this question in adult male frogs of a non-declining species (Litoria wilcoxii). Frogs were sampled for (1) seasonal hormone (testosterone and corticosterone), color and disease profiles, (2) the relationship between disease infection status and hormone levels or dorsal color, (3) subclinical effects of Bd by investigating disease load and hormone level, and (4) reproductive and stress hormone relationships independent of disease. Testosterone levels and color score varied seasonally (throughout the spring/summer months) while corticosterone levels remained stable. Frogs with high Bd prevalence had significantly higher corticosterone levels and lower testosterone levels compared to uninfected frogs, and no differences in color were observed. There was a significant positive correlation between disease load and corticosterone levels, and a significant negative relationship between disease load and testosterone. Our field data provides novel evidence that increased physiological stress response associated with Bd infection in wild frogs, could suppress reproduction by down-regulating gonadal hormones in amphibians, however the impacts on reproductive output is yet to be established.


Medicare's Bundled Payment initiative: most hospitals are focused on a few high-volume conditions.
The Bundled Payments for Care Improvement initiative is a federally funded innovation model mandated by the Affordable Care Act. It is designed to help transition Medicare away from fee-for-service payments and toward bundling a single payment for an episode of acute care in a hospital and related postacute care in an appropriate setting. While results from the initiative will not be available for several years, current data can help provide critical early insights. However, little is known about the participating organizations and how they are focusing their efforts. We identified participating hospitals and used national Medicare claims data to assess their characteristics and previous spending patterns. These hospitals are mostly large, nonprofit, teaching hospitals in the Northeast, and they have selectively enrolled in the bundled payment initiative covering patient conditions with high clinical volumes. We found no significant differences in episode-based spending between participating and nonparticipating hospitals. Postacute care explains the largest variation in overall episode-based spending, signaling an opportunity to align incentives across providers. However, the focus on a few selected clinical conditions and the high degree of integration that already exists between enrolled hospitals and postacute care providers may limit the generalizability of bundled payment across the Medicare system.


Linking hydrogen (δ2H) isotopes in feathers and precipitation: sources of variance and consequences for assignment to isoscapes.
Tracking small migrant organisms worldwide has been hampered by technological and recovery limitations and sampling bias inherent in exogenous markers. Naturally occurring stable isotopes of H (δ(2)H) in feathers provide an alternative intrinsic marker of animal origin due to the predictable spatial linkage to underlying hydrologically driven flow of H isotopes into foodwebs. This approach can assess the likelihood that a migrant animal originated from a given location(s) within a continent but requires a robust algorithm linking H isotopes in tissues of interest to an appropriate hydrological isotopic spatio-temporal pattern, such as weighted-annual rainfall. However, a number of factors contribute to or alter expected isotopic patterns in animals. We present results of an extensive investigation into taxonomic and environmental factors influencing feather δ(2)H patterns across North America. Stable isotope data were measured from 544 feathers from 40 species and 140 known locations. For δ(2)H, the most parsimonious model explaining 83% of the isotopic variance was found with amount-weighted growing-season precipitation δ(2)H, foraging substrate and migratory strategy. This extensive H isotopic analysis of known-origin feathers of songbirds in North America and elsewhere reconfirmed the strong coupling between tissue δ(2)H and global hydrologic δ(2)H patterns, and accounting for variance associated with foraging substrate and migratory strategy, can be used in conservation and research for the purpose of assigning birds and other species to their approximate origin.


Displacement of the predominant dengue virus from type 2 to type 1 with a subsequent genotype shift from IV to I in Surabaya, Indonesia 2008-2010.
Indonesia has annually experienced approximately 100,000 reported cases of dengue fever (DF) and dengue hemorrhagic fever (DHF) in recent years. However, epidemiological surveys of dengue viruses (DENVs) have been limited in this country. In Surabaya, the second largest city, a single report indicated that dengue virus type 2 (DENV2) was the predominant circulating virus in 2003-2005. We conducted three surveys in Surabaya during: (i) April 2007, (ii) June 2008 to April 2009, and (iii) September 2009 to December 2010. A total of 231 isolates were obtained from dengue patients and examined by PCR typing. We found that the predominant DENV shifted from type 2 to type 1 between October and November 2008. Another survey using wild-caught mosquitoes in April 2009 confirmed that dengue type 1 virus (DENV1) was the predominant type in Surabaya. Phylogenetic analyses of the nucleotide sequences of the complete envelope gene of DENV1 indicated that all 22 selected isolates in the second survey belonged to genotype IV and all 17 selected isolates in the third survey belonged to genotype I, indicating a genotype shift between April and September 2009. Furthermore, in December 2010, isolates were grouped into a new clade of DENV1 genotype I, suggesting clade shift between September and December 2010. According to statistics reported by the Surabaya Health Office, the proportion of DHF cases among the total number of dengue cases increased about three times after the type shift in 2008. In addition, the subsequent genotype shift in 2009 was associated with the increased number of total dengue cases. This indicates the need for continuous surveillance of circulating viruses to predict the risk of DHF and DF.


Tests of General Relativity with GW150914.
The LIGO detection of GW150914 provides an unprecedented opportunity to study the two-body motion of a compact-object binary in the large-velocity, highly nonlinear regime, and to witness the final merger of the binary and the excitation of uniquely relativistic modes of the gravitational field. We carry out several investigations to determine whether GW150914 is consistent with a binary black-hole merger in general relativity. We find that the final remnant's mass and spin, as determined from the low-frequency (inspiral) and high-frequency (postinspiral) phases of the signal, are mutually consistent with the binary black-hole solution in general relativity. Furthermore, the data following the peak of GW150914 are consistent with the least-damped quasinormal mode inferred from the mass and spin of the remnant black hole. By using waveform models that allow for parametrized general-relativity violations during the inspiral and merger phases, we perform quantitative tests on the gravitational-wave phase in the dynamical regime and we determine the first empirical bounds on several high-order post-Newtonian coefficients. We constrain the graviton Compton wavelength, assuming that gravitons are dispersed in vacuum in the same way as particles with mass, obtaining a 90%-confidence lower bound of 10^{13} km. In conclusion, within our statistical uncertainties, we find no evidence for violations of general relativity in the genuinely strong-field regime of gravity.


Comparison of antibiotic resistance and virulence factors in pigmented and non-pigmented Pseudomonas aeruginosa.
Pseudomonas aeruginosa produces multiple virulence factors that have been implicated in pathogenesis and quorum sensing. The aim of this study was to determine differences in the virulence factors of pigmented and non-pigmented P aeruginosa isolates. Associations were assessed between pigment production (pyocyanin and pyoverdin) and production of DNase, elastase, lipase, protease, siderophore, twitching motility, antibiotic resistance patterns and virulence-associated genes in 57 non-duplicate P aeruginosa isolates from wounds, sputum, urine, high vaginal swab (HVS), ear, eye and respiratory tract swabs and aspirates of peritoneum and ulcers. Most (82.5%) of the isolates produced either pigment. Pigmented isolates produced more frequently and significant more (p < 0.05) DNase, elastase, lipase protease, and siderophore. Imipenem was the only antibiotic to which all isolates were susceptible (p < 0.05), while 93% and 32% were resistant to tetracycline and norfloxacin, respectively. There was however no significant difference between pigmented and non-pigmented isolates when antibiotic resistance was compared. While isolates had multiple virulence-associated genes, exoS (51%), rhlA (37%) and rhlB (46%) were the predominant genes detected. Except for exoY, genes were present in pigmented isolates more frequently than in non-pigmented isolates. The results of this study suggest that antibiotic resistance per se might not be associated with the pigment production in P aeruginosa. However pigment production appeared to be more significantly associated with multi-drug resistance, presence of virulence-associated genes, and expression of certain virulence factors, most notably elastase, protease, siderophore and DNase activity. Since pigment production is easy to determine, this might to be a good starting point to identify the virulence status of an isolate.


Patient complexity and diabetes quality of care in rural settings.
Even though pay-for-performance programs are being rapidly implemented, little is known about how patient complexity affects practice-level performance assessment in rural settings. We sought to determine the association between patient complexity and practice-level performance in the rural United States. Using baseline data from a trial aimed at improving diabetes care, we determined factors associated with a practice's proportion of patients having controlled diabetes (hemoglobin A1c<or=7%): patient socioeconomic factors, clinical factors, difficulty with self-testing of blood glucose, and difficulty with keeping appointments. We used linear regression to adjust the practice-level proportion with A1c controlled for these factors. We compared practice rankings using observed and expected performance and classified practices into hypothetical pay-for-performance categories. Rural primary care practices (n=135) in 11 southeastern states provided information for 1641 patients with diabetes. For practices in the best quartile of observed control, 76.1% of patients had controlled diabetes vs 19.3% of patients in the worst quartile. After controlling for other variables, proportions of diabetes control were 10% lower in those practices whose patients had the greatest difficulty with either self testing or appointment keeping (p<.05 for both). Practice rankings based on observed and expected proportion of A1c control showed only moderate agreement in pay-for-performance categories (kappa=0.47; 95% confidence interval, 0.32-0.56; p<001). Basing public reporting and resource allocation on quality assessment that does not account for patient characteristics may further harm this vulnerable group of patients and physicians.


Improved free R factors for cross-validation of macromolecular structure - importance for real-space refinement.
Improvements in free R cross-validation are based on changed scaling procedures and the use, in map calculation, of estimates of the validation amplitudes which are independent of the actual observed values. The deleterious effects of the omitted test data are mitigated by reduction of the test-set size, which is made possible by constraining test and working sets to share the same scaling coefficients, thereby reducing the degrees of freedom and the dependence of free R on data selection. Further improvements come with use of a modified free R factor, R freeTA. Instead of omitting the validation reflections from map calculation, their amplitudes are replaced by the average of resolution peers that is (nearly) independent of the actual cross-validation amplitudes. The improvements are relevant to model building, phase refinement by density modification and especially to real-space refinement. Although for real data at about 3 A resolution, free R factors of about 0.25 are affected little, the precision of the structure is improved by about 0.1 A. Tests with simulated data show that with good agreement between observed and calculated amplitudes (as in very high resolution studies or simulated refinement tests), free R factors can be improved by factors greater than two.


[Feeding patterns of Triatoma pseudomaculata in the state of Ceara, Brazil].
T. pseudomaculata, a peridomicilar species, has low rates of T. cruzi infection. The occurrence of this triatomine in the domicile and its feeding patterns was investigated to identify potential T. cruzi reservoirs. Nine-hundred and twenty-one specimens of T. pseudomaculata were captured from January 2001 to July 2002 in 13 southern municipalities of the state of Ceara, Brazil. The intestinal contents of the triatomines was removed, spread in a filter paper and tested for the following antisera: bird, cat, cockroach, dog, human, lizard, opossum, ox/goat, pig, and rodent. The presence of T. cruzi was investigated by wet mount microscopic exam and culture (NNN+LIT) of intestinal contents. Of the total studied, 184 (90.6%) were positive for the tested antisera: bird (62.5%)> rodent (33.7%)> dog (20.1%)> opossum (9.8%)> lizard and ox/goat (5%)> cat (2.7%)> pig and cockroach (2.2%)> human (1.6%). Blood meals ranged from none (non-reactive) to four as follows: non-reactive (9.4%), one (57.1%), two (26%), three (7%), and four (0.5%). Only three specimens (1.6%) had T. cruzi infection. The low incidence of human blood meal shows that T. pseudomaculata is well-adjusted to the peridomicile. However, the epidemiological vigilance in this region is key due to this species' proximity to domiciles.


Whiplash: assessing the validity of diagnostic tests in a cervical sensory disturbance.
To determine the ability of two diagnostic tests that examine sensory disturbance in whiplash patients to discriminate between 'extreme' groups. The neuromuscular theories have been accepted as explanations of the symptoms after a whiplash injury. Dutch manual therapists often use the diagnostic tests under study to diagnose and treat sensory disturbances after such an injury. The validity of a test needs to be assessed before its efficacy as a treatment in whiplash patients can be tested. The aim of this study was to validate two diagnostic tests and to initiate further research on the efficacy of a treatment of a sensory disturbance in whiplash patients. Twelve subjects with chronic symptoms (> 3 months) after a whiplash injury (patient group) and 18 subjects without any head or neck problems (control group) were studied. The tests under study were the extension test and the coordination test. All researchers were blind to the characteristics of the subjects. The extension test and the coordination test were able to discriminate adequately between subjects with symptoms after a whiplash injury (patients) and subjects without any head or neck complaints (control subjects). Patients clearly show a smaller degree of extension compared with the control subjects and an increase of extension movement with external fixation. The sensitivity as well as the specificity of the coordination test were good (both > .80). These diagnostic tests seemed to be valid instruments for discriminating between whiplash patients with symptoms and healthy people.


Assessment of the relationship between circadian variations of salivary melatonin levels and type I collagen metabolism in postmenopausal obese women.
Few experimental and clinical studies show that melatonin (MEL) can play a significant part to modulate circadian bone metabolism. On this basis it was suggested that MEL secretion which altered during 24-h in obese women could be of importance to regulate bony mass defect after menopause. The aim of the study was to prove if there were any connection between changes in 24-h profile of serum MEL levels and circadian metabolism of type I collagen in postmenopausal women with visceral obesity. The relationship of 24-h profile of salivary MEL and circadian metabolism of type I collagen (as assessed by measuring saliva concentrations of carboxyterminal propeptide of type I procollagen--PICP and cross-linked carboxyterminal telopeptide of type I collagen--ICTP) was investigated in 26 women with visceral obesity (33.5 < BMI < 42.1 kg/m(2)) and 18 healthy volunteers with correct body mass (21 < BMI < 24.5 kg/m(2); 0.73 < WHR < 0.76). The specimens were collected at subjects' home at 3 h intervals during a 24 h span. The age range of all subjects was 52-60 years. In all the obese women studied a tendency to suppress circadian levels of tested biochemical markers of bone metabolism was observed (especially regarding ICTP); those alterations were accompanied by substantial increment in MEL concentrations during the day. Significant and negative correlation was found between values of acrophase MEL and PICP rhythms and both amplitude and acrophase of MEL and ICTP rhythms. Our results confirm hypothesis that alterations in MEL concentrations might have a protective effect against postmenopausal loss of bone mass.


Metastatic tumor evolution and organoid modeling implicate TGFBR2 as a cancer driver in diffuse gastric cancer.
Gastric cancer is the second-leading cause of global cancer deaths, with metastatic disease representing the primary cause of mortality. To identify candidate drivers involved in oncogenesis and tumor evolution, we conduct an extensive genome sequencing analysis of metastatic progression in a diffuse gastric cancer. This involves a comparison between a primary tumor from a hereditary diffuse gastric cancer syndrome proband and its recurrence as an ovarian metastasis. Both the primary tumor and ovarian metastasis have common biallelic loss-of-function of both the CDH1 and TP53 tumor suppressors, indicating a common genetic origin. While the primary tumor exhibits amplification of the Fibroblast growth factor receptor 2 (FGFR2) gene, the metastasis notably lacks FGFR2 amplification but rather possesses unique biallelic alterations of Transforming growth factor-beta receptor 2 (TGFBR2), indicating the divergent in vivo evolution of a TGFBR2-mutant metastatic clonal population in this patient. As TGFBR2 mutations have not previously been functionally validated in gastric cancer, we modeled the metastatic potential of TGFBR2 loss in a murine three-dimensional primary gastric organoid culture. The Tgfbr2 shRNA knockdown within Cdh1-/-; Tp53-/- organoids generates invasion in vitro and robust metastatic tumorigenicity in vivo, confirming Tgfbr2 metastasis suppressor activity. We document the metastatic differentiation and genetic heterogeneity of diffuse gastric cancer and reveal the potential metastatic role of TGFBR2 loss-of-function. In support of this study, we apply a murine primary organoid culture method capable of recapitulating in vivo metastatic gastric cancer. Overall, we describe an integrated approach to identify and functionally validate putative cancer drivers involved in metastasis.


Effect of plant age, larval age, and fertilizer treatment on resistance of a cry1Ab-transformed aromatic rice to lepidopterous stem borers and foliage feeders.
The resistance of vegetative, booting, and flowering stage plants of a variety of an aromatic rice, Oryza sativa L., transformed with a Bacillus thuringiensis Berliner cry1Ab gene under control of the maize phosphoenolpyruvate carboxylase (PEPC) promoter was evaluated against four lepidopterous rice pests--the stem borers Chilo suppressalis (Walker) (Lepidoptera: Crambidae) and Scirpophaga incertulas (Walker) (Lepidoptera: Pyralidae), and the foliage feeders Cnaphalocrocis medinalis Guenée (Lepidoptera: Pyralidae) and Naranga aenescens Moore (Lepidoptera: Noctuidae). Plants of the cry1Ab-transformed line (no. 827) were more resistant to young larvae of S. incertulas, C. suppressalis, and C. medinalis than control plants at the vegetative stage but not at the flowering stage. Survival of 10-d-old stem borer larvae did not differ on cry1Ab plants and control plants at either the vegetative or flowering stage, but the development of 10-d-old C. suppressalis larvae was retarded on the vegetative stage cry1Ab plants. Immunological analysis also showed an apparent decline in Cry1Ab titer in leaf blades and leaf sheaths at the reproductive stage. In experiments comparing three fertilizer treatments (NPK, PK, and none), there was a significant interaction between fertilizer treatment and variety on larval survival only in whole-plant assays at booting stage with C. suppressalis. On cry1Ab plants, larval survival did not differ significantly among the three fertilizer levels, whereas on control plants survival was highest with the NPK treatment. cry1Ab plants tested at the sixth and seventh generations after transformation were more resistant than control plants to N. aenescens and C. suppressalis, respectively, suggesting that gene silencing will not occur in line 827. The results of the experiments are discussed in terms of resistance management for B. thuringiensis toxins in rice.


Dynamics of vesicular-arbuscular mycorrhizae during old field succession.
The species composition of vesicular-arbuscular mycorrhizal (VAM) fungal communities changed during secondary succession of abandoned fields based on a field to forest chronosequence. Twenty-five VAM fungal species were identified. Seven species were clearly early successional and five species were clearly late successional. The total number of VAM fungal species did not increase with successional time, but diversity as measured by the Shannon-Wiener index tended to increase, primarily because the community became more even as a single species, Glomus aggregatum, became less dominant in the older sites. Diversity of the VAM fungal community was positively correlated with soil C and N. The density of VAM fungi, as measured by infectivity and total spore count, first increased with time since abandonment and then decreased in the late successional forest sites. Within 12 abandoned fields, VAM fungal density increased with increasing soil pH, H2O soluble soil C, and root biomass, but was inversely related to extractable soil P and percent cover of non-host plant species. The lower abundance of VAM fungi in the forest sites compared with the field sites agrees with the findings of other workers and corresponds with a shift in the dominant vegetation from herbaceous VAM hosts to woody ectomycorrhizal hosts.


Tumor fistulization associated with targeted therapy: computed tomographic findings and clinical consequences.
To describe the computed tomographic (CT) appearances and clinical consequences of tumor fistulization as a complication of targeted therapy for cancer. The committee on human research approved this Health Insurance Portability and Accountability Act-compliant study and waived written informed consent. Based on the records of the senior author and our multidisciplinary Tumor Boards, we retrospectively identified 4 patients (1 man and 3 women with a mean age of 55.25 years; range, 47 to 64 years) who developed tumor fistulization while being treated with targeted therapy consisting of sunitinib (n = 2); bevacizumab (n = 1); and XL184, an investigational c-Met inhibitor (n = 1). All available clinical, imaging, and histopathological records were reviewed, with particular emphasis on treatment administered, CT findings, and clinical course. All 4 patients developed fistulae from large metastatic deposits in the abdomen (mean size before treatment, 10.55 cm; range, 7.4-13.4 cm) to the gastrointestinal tract, and one patient also developed fistulae from a lung metastasis of undetermined size to the bronchial tree. All fistulae manifested as the appearance of air within a pre-existing tumor mass. At the time of fistula detection, disease at other sites in the 4 patients showed signs of regression (n = 1), progression (n = 2), or stability (n = 1). Currently, one patient is alive without evidence of disease, and the 3 other patients are deceased. Targeted therapy can be associated with tumor fistulization to the gastrointestinal tract or tracheobronchial tree; familiarity with the CT findings should facilitate the diagnosis of this complication, which seems to be of variable and patient-specific prognostic significance.


Quorum sensing and the social evolution of bacterial virulence.
The ability of pathogenic bacteria to exploit their hosts depends upon various virulence factors, released in response to the concentration of small autoinducer molecules that are also released by the bacteria [1-5]. In vitro experiments suggest that autoinducer molecules are signals used to coordinate cooperative behaviors and that this process of quorum sensing (QS) can be exploited by individual cells that avoid the cost of either producing or responding to signal [6, 7]. However, whether QS is an exploitable social trait in vivo, and the implications for the evolution of virulence [5, 8-10], remains untested. We show that in mixed infections of the bacterium Pseudomonas aeruginosa, containing quorum-sensing bacteria and mutants that do not respond to signal, virulence in an animal (mouse) model is reduced relative to that of an infection containing no mutants. We show that this is because mutants act as cheats, exploiting the cooperative production of signal and virulence factors by others, and hence increase in frequency. This supports the idea that the invasion of QS mutants in infections of humans [11-13] is due to their social fitness consequences [6, 7, 14] and predicts that increased strain diversity will select for lower virulence.


Daytime ambulatory systolic blood pressure is more effective at predicting mortality than clinic blood pressure.
To assess the prognostic value of daytime ambulatory blood pressure compared with routine clinic blood pressure in determining mortality. Prospective multicentre study in 48 general practices in Oxfordshire, a hypertension clinic in Oxford and a hypertension clinic in London. A cohort of 10 129 patients from Oxford and London was followed up for a median of 8.2 years. Nine hundred and one deaths were recorded (8.9%) corresponding to a mortality rate per 1000 years of follow-up of 10.8 (99% confidence interval 9.9-11.8). Comparing the highest quartile for systolic ambulatory blood pressure with the lowest (>or=160 vs. <135 mmHg) gives an estimated age sex-adjusted hazard ratio for mortality of 1.51 (95% confidence interval 1.25-1.83, P<0.001). The corresponding comparison for clinic systolic blood pressure (>or=174 vs. <148 mmHg) results in a hazard ratio of 1.02 (95% confidence interval 0.84-1.24, P=0.9). Comparing ambulatory versus clinic systolic blood pressure (10 mmHg groupings) using nested statistical modelling, removal of the ambulatory blood pressure term from the baseline Cox model (nine 10 mmHg categories) resulted in a highly significant likelihood ratio test statistic of 52.5 (df=8, P<0.0001). The corresponding result for removal of the clinic blood pressure term was 18.1 (df=8, P=0.02), thus reinforcing the finding that ambulatory blood pressure monitoring has greater prognostic significance. Ambulatory blood pressure was also a better predictor of all-cause mortality both in patients taking medication and those not taking medication at the time of monitoring. Daytime ambulatory blood pressure monitoring is a much better prognostic indicator of all-cause mortality than clinic blood pressure.


Pharmacokinetic and pharmacodynamic analysis of the actions of D-amphetamine and D-methamphetamine on the dopamine terminal.
To establish whether the actions of D-amphetamine (Amp) and D-methamphetamine (MeAmp) on the striatal dopamine system were equipotent, pharmacokinetic profiles of each drug were applied to an analysis of their respective induced dopamine efflux profiles. Amp or MeAmp (1 and 5 mg/kg i.v.) was administered to chloral hydrate-anesthetized rats; plasma and brain kinetics were then assessed from 5 to 60 min. Dose-dependent increases in Amp and MeAmp plasma levels resulted in proportional increases in striatum levels that were equivalent for both drugs; elimination rates also were similar and were characterized by a first-order decay process. After MeAmp administration, low levels of brain MeAmp metabolites were detected throughout the 1-hr time period; relative to MeAmp, Amp and p-hydroxy-MeAmp levels were less than 10 and 1%, respectively. The drug-induced dopamine efflux profiles in the striatum were characterized by microdialysis; Amp and MeAmp (1, 2.5 and 5 mg/kg i.v.) effected equivalent, dose-dependent increases in extracellular dopamine levels. For both drugs at 5- and 10-min postinjection, increases in drug striatum levels preceded increases in dopamine efflux. In contrast, from the time of the peak dopamine responses observed at 10 to 20 min until the end of the study at 90 min, changes in striatal drug levels were correlated with extracellular dopamine levels; this correlation was similar for both drugs. These results indicate that Amp and MeAmp pharmacokinetics and their subsequent dopamine responses in the striatum are equivalent. The pharmacokinetic analysis can be extended to the interpretation of other comparative studies that assess effects of Amp and MeAmp.(ABSTRACT TRUNCATED AT 250 WORDS)


Expression of T helper cell-associated inflammatory mediator mRNAs in cells of bronchoalveolar lavage fluid samples and oxygen concentration in arterial blood samples from healthy horses exposed to hyperbaric oxygen.
OBJECTIVE To evaluate the mRNA expression of T helper (Th)1, Th2, and Th17 cell-associated inflammatory mediators in cells of bronchoalveolar lavage fluid samples collected from healthy horses exposed to hyperbaric oxygen (HBO) and to monitor blood oxygen concentration during and following HBO therapy. ANIMALS 8 healthy horses. PROCEDURES In a randomized controlled crossover design study, each horse was exposed (beginning day 1) to 100% oxygen at a maximum of 3 atmospheres absolute (304 kPa) daily for 10 days or ambient air at atmospheric pressure in the HBO chamber for an equivalent amount of time (control). Bronchoalveolar lavage fluid samples were collected on days 0 and 10. After validation of candidate reference genes, relative mRNA expressions of various innate inflammatory, Th1 cell-derived, Th2 cell-derived (including eotaxin-2), Th17 cell-derived, and regulatory cytokines were measured by quantitative PCR assays. For 3 horses, arterial blood samples were collected for blood gas analysis during a separate HBO session. RESULTS The optimal combination of reference genes was glyceraldehyde-3-phosphate dehydrogenase, hypoxanthine ribosyltransferase, and ribosomal protein L32. Compared with day 0 findings, expression of eotaxin-2 mRNA was significantly lower (0.12-fold reduction) and the percentage of neutrophils in bronchoalveolar lavage fluid samples was significantly lower on day 10 when horses received HBO therapy. Values of Pao2 rapidly increased (> 800 mm Hg) but immediately decreased to pretreatment values when HBO sessions ended. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that HBO therapy does not increase mRNA expression of inflammatory cytokines, but reduces eotaxin-2 mRNA transcription. The Pao2 increase was transient with no cumulative effects of HBO.


Gastrointestinal signs and a need for nutritional management may persist long term in dogs and cats undergoing resection of the ileocolic junction: 35 cases (2008-2020).
To evaluate the effects of ileocecocolic junction (ICJ) resection on gastrointestinal signs, biochemical parameters, and nutritional variables in dogs and cats. 20 dogs and 15 cats that underwent ICJ resection between January 2008 and June 2020. Medical records of dogs and cats that underwent ICJ resection were reviewed, and clinical signs, laboratory abnormalities, and nutritional information were obtained. Additional follow-up information was obtained by contacting primary care veterinarians or owners. A subset of dogs (n = 6) and cats (2) were evaluated in the hospital via clinical examination, clinicopathologic testing, nutritional testing, and abdominal ultrasound. Twenty dogs and 15 cats underwent resection of the ICJ for treatment of a variety of conditions. Ten of 20 dogs (50%) and 11/15 cats (73%) were reported by their owners to have a good long-term outcome based on the lack of long-term gastrointestinal signs or the ability to control gastrointestinal signs with diet and supplements alone. Despite owner-reported good outcomes, long-term diarrhea, weight loss, and muscle loss were common. Of the 6 dogs evaluated in the hospital, 3/6 (50%) had muscle loss, 2/6 (33%) had low taurine concentrations, and 1 dog each had low cobalamin, folate, 25-hydroxyvitamin D, and ionized calcium. Neither of the 2 cats evaluated in the hospital had nutritional abnormalities identified. Owners should be informed of the possibility of long-term gastrointestinal clinical signs and the potential need for long-term nutritional management after ICJ resection.


Molecular mechanism and energetics of clamp assembly in Escherichia coli. The role of ATP hydrolysis when gamma complex loads beta on DNA.
Escherichia coli DNA polymerase III holoenzyme is a multisubunit composite containing the beta sliding clamp and clamp loading gamma complex. The gamma complex requires ATP to load beta onto DNA. A two-color fluorescence spectroscopic approach was utilized to study this system, wherein both assembly (red fluorescence; X-rhodamine labeled DNA anisotropy assay) and ATP hydrolysis (green fluorescence; phosphate binding protein assay) were simultaneously measured with millisecond timing resolution. The two temporally correlated stopped-flow signals revealed that a preassembled beta. gamma complex composite rapidly binds primer/template DNA in an ATP hydrolysis independent step. Once bound, two molecules of ATP are rapidly hydrolyzed (approximately 34 s(-1)). Following hydrolysis, gamma complex dissociates from the DNA ( approximately 22 s(-1)). Once dissociated, the next cycle of loading is severely compromised, resulting in steady-state ATP hydrolysis rates with a maximum of only approximately 3 s(-1). Two single-site beta dimer interface mutants were examined which had impaired steady-state rates of ATP hydrolysis. The pre-steady-state correlated kinetics of these mutants revealed a pattern essentially identical to wild type. The anisotropy data showed that these mutants decrease the steady-state rates of ATP hydrolysis by causing a buildup of "stuck" binary-ternary complexes on the primer/template DNA.


Plant-Mediated RNAi for Controlling Apolygus lucorum.
The polyphagous mirid bug Apolygus lucorum (Heteroptera: Miridae) is a serious pest of agricultural crops in China, with more than 200 species of host plants including two very important crops, maize and soybean. Currently, prevention and control of A. lucorum rely mainly on chemical pesticides that cause environmental as well as health related problems. Plant-mediated RNAi has proven to offer great potential for pest control in the past decade. In this study, we screened and obtained seven candidate genes (Alucβ-actin, AlucV-ATPase-A/D/E, AlucEif5A, AlucEcR-A, AlucIAP) by injection-based RNAi which produced A. lucorum mortality rates of 46.01-82.32% at day 7 after injection. Among them, the plant-mediated RNAi of AlucV-ATPase-E was successfully introduced into transgenic maize and soybean, and the populations of A. lucorum were significantly decreased following feeding on the transgenic maize and soybean. These results are intended to provide helpful insight into the generation of bug-resistant plants through a plant-mediated RNAi strategy.


[Molecular pharmacology and physiology of nociceptin].
The family of the G protein-coupled opioid receptors was recently extended by a novel member that did not bind any of the typical opioid receptor ligands. Identification of the orphan receptor in this way led to the advent of "reverse pharmacology" to identify the corresponding physiological ligands. Nociceptin, a heptadecapeptide, which was discovered as an endogenous ligand, first, attracted us by its reported nociceptive or anti-opioid actions. However, following studies revealed that this peptide has both nociceptive and antinociceptive actions under different conditions; e.g., administration routes or doses affect its actions. In our recent studies using a unique peripheral peripheral nociception test, nociceptin given locally at lower doses was found to produce nociception through substance P release from nociceptor endings, while at higher doses, it produced antinociceptive actions through an inhibition of phospholipase C activity stimulated by nociceptive substances. Such hypothetical mechanisms can be applied to the mechanisms of nociceptin-induced paradoxical actions in the central nervous system. The physiological role of nociceptin has recently been reported using nociceptin receptor knock-out mice. Following the report of a hearing problem in such mice, the nociceptin receptor was found to be involved in the development of morphine analgesic tolerance. In this review, more findings on the physiological roles of nociceptin or its receptor, such as pain control and memory-learning, are discussed on the basis of reports using nociceptin receptor knock-out mice.


Structures of cage, prism, and book isomers of water hexamer from broadband rotational spectroscopy.
Theory predicts the water hexamer to be the smallest water cluster with a three-dimensional hydrogen-bonding network as its minimum energy structure. There are several possible low-energy isomers, and calculations with different methods and basis sets assign them different relative stabilities. Previous experimental work has provided evidence for the cage, book, and cyclic isomers, but no experiment has identified multiple coexisting structures. Here, we report that broadband rotational spectroscopy in a pulsed supersonic expansion unambiguously identifies all three isomers; we determined their oxygen framework structures by means of oxygen-18-substituted water (H(2)(18)O). Relative isomer populations at different expansion conditions establish that the cage isomer is the minimum energy structure. Rotational spectra consistent with predicted heptamer and nonamer structures have also been identified.


Single-particle tracking as a quantitative microscopy-based approach to unravel cell entry mechanisms of viruses and pharmaceutical nanoparticles.
Highly sensitive fluorescence microscopy techniques allow single nanoparticles to be tracked during their uptake into living cells with high temporal and spatial resolution. From analysis of the trajectories, random motion can be discriminated from active transport and the average transport velocity and/or diffusion coefficient determined. Such an analysis provides important information regarding the uptake pathway and location of viruses and nanoparticles. In this review, we give an introduction into single-particle tracking (SPT) and determination of the mean-squared displacement. We also give an overview of recent advances in SPT. These include millisecond alternating-laser excitation for removal of spectral crosstalk, alternating wide-field (WF), and total internal reflection fluorescence (TIRF) microscopy for sensitive experiments at the plasma membrane and three-dimensional tracking strategies. Throughout the review, we highlight recent advances regarding the entry (and egress) of natural and artificial viruses obtained via SPT.


Hospital-acquired catheter-associated urinary tract infection: documentation and coding issues may reduce financial impact of Medicare's new payment policy.
To evaluate whether hospital-acquired catheter-associated urinary tract infections (CA-UTIs) are accurately documented in discharge records with the use of International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes so that nonpayment is triggered, as mandated by the Centers for Medicare and Medicaid Services (CMS) Hospital-Acquired Conditions Initiative. We conducted a retrospective medical record review of 80 randomly selected adult discharges from May 2006 through September 2007 from the University of Michigan Health System (UMHS) with secondary-diagnosis urinary tract infections (UTIs). One physician-abstractor reviewed each record to categorize UTIs as catheter associated and/or hospital acquired; these results (considered "gold standard") were compared with diagnosis codes assigned by hospital coders. Annual use of the catheter association code (996.64) by UMHS coders was compared with state and US rates by using Healthcare Cost and Utilization Project data. Patient mean age was 58 years; 56 (70%) were women; median length of hospital stay was 6 days; 50 patients (62%) used urinary catheters during hospitalization. Hospital coders had listed 20 secondary-diagnosis UTIs (25%) as hospital acquired, whereas physician-abstractors indicated that 37 (46%) were hospital acquired. Hospital coders had identified no CA-UTIs (code 996.64 was never used), whereas physician-abstractors identified 36 CA-UTIs (45%; 28 hospital acquired and 8 present on admission). Catheter use often was evident only from nursing notes, which, unlike physician notes, cannot be used by coders to assign discharge codes. State and US annual rates of 996.64 coding (approximately 1% of secondary-diagnosis UTIs) were similar to those at UMHS. Hospital coders rarely use the catheter association code needed to identify CA-UTI among secondary-diagnosis UTIs. Coders often listed a UTI as present on admission, although the medical record indicated that it was hospital acquired. Because coding of hospital-acquired CA-UTI seems to be fraught with error, nonpayment according to CMS policy may not reliably occur.


Bioinformatics analysis of the early inflammatory response in a rat thermal injury model.
Thermal injury is among the most severe forms of trauma and its effects are both local and systemic. Response to thermal injury includes cellular protection mechanisms, inflammation, hypermetabolism, prolonged catabolism, organ dysfunction and immuno-suppression. It has been hypothesized that gene expression patterns in the liver will change with severe burns, thus reflecting the role the liver plays in the response to burn injury. Characterizing the molecular fingerprint (i.e., expression profile) of the inflammatory response resulting from burns may help elucidate the activated mechanisms and suggest new therapeutic intervention. In this paper we propose a novel integrated framework for analyzing time-series transcriptional data, with emphasis on the burn-induced response within the context of the rat animal model. Our analysis robustly identifies critical expression motifs, indicative of the dynamic evolution of the inflammatory response and we further propose a putative reconstruction of the associated transcription factor activities. Implementation of our algorithm on data obtained from an animal (rat) burn injury study identified 281 genes corresponding to 4 unique profiles. Enrichment evaluation upon both gene ontologies and transcription factors, verifies the inflammation-specific character of the selections and the rationalization of the burn-induced inflammatory response. Conducting the transcription network reconstruction and analysis, we have identified transcription factors, including AHR, Octamer Binding Proteins, Kruppel-like Factors, and cell cycle regulators as being highly important to an organism's response to burn response. These transcription factors are notable due to their roles in pathways that play a part in the gross physiological response to burn such as changes in the immune response and inflammation. Our results indicate that our novel selection/classification algorithm has been successful in selecting out genes with play an important role in thermal injury. Additionally, we have demonstrated the value of an integrative approach in identifying possible points of intervention, namely the activation of certain transcription factors that govern the organism's response.


Hippocampal sclerosis dementia differs from hippocampal sclerosis in frontal lobe degeneration.
Hippocampal sclerosis (HS) is characterized by selective neuronal loss and gliosis in CA1 and the subiculum and has been associated with several disorders, including Alzheimer's disease, frontotemporal lobar degeneration with ubiquitin immunoreactive inclusions (FTLD-U), vascular dementia and some tauopathies. In some cases, HS is not associated with other degenerative pathologies. Such cases are sometimes referred to as HS dementia (HSD). Differences between HSD and HS in the setting of FTLD-U have not been systematically investigated. To this end, eight cases of HSD and ten cases of HS associated with FTLD-U were studied with Nissl and periodic acid-Schiff stains to assess neuronal loss and corpora amylacea, respectively. Sections were immunostained with antibodies to glial fibrillary acidic protein, HLA-DR and synaptophysin and immunoreactivity was measured with image analysis in CA1 and the subiculum of each case. Additionally, sections were immunostained with antibodies to 4-R tau to determine the presence of argyrophilic grains. HSD was different from HS associated with FTLD-U. Specifically, it was more common in the elderly, and it was associated with more marked neuronal and synaptic loss and with greater reactive gliosis. Corpora amylacea tended to be more frequent in HSD than in FTLD-U, but there was no difference in frequency of argyrophilic grains.


A multichannel integrated circuit for electrical recording of neural activity, with independent channel programmability.
Since a few decades, micro-fabricated neural probes are being used, together with microelectronic interfaces, to get more insight in the activity of neuronal networks. The need for higher temporal and spatial recording resolutions imposes new challenges on the design of integrated neural interfaces with respect to power consumption, data handling and versatility. In this paper, we present an integrated acquisition system for in vitro and in vivo recording of neural activity. The ASIC consists of 16 low-noise, fully-differential input channels with independent programmability of its amplification (from 100 to 6000 V/V) and filtering (1-6000 Hz range) capabilities. Each channel is AC-coupled and implements a fourth-order band-pass filter in order to steeply attenuate out-of-band noise and DC input offsets. The system achieves an input-referred noise density of 37 nV/√Hz, a NEF of 5.1, a CMRR > 60 dB, a THD < 1% and a sampling rate of 30 kS/s per channel, while consuming a maximum of 70 μA per channel from a single 3.3 V. The ASIC was implemented in a 0.35 μm CMOS technology and has a total area of 5.6 × 4.5 mm². The recording system was successfully validated in in vitro and in vivo experiments, achieving simultaneous multichannel recordings of cell activity with satisfactory signal-to-noise ratios.