Classical density functional theory in the canonical ensemble.
Classical density functional theory for finite temperatures is usually formulated in the grand-canonical ensemble where arbitrary variations of the local density are possible. However, in many cases the systems of interest are closed with respect to mass, e.g., canonical systems with fixed temperature and particle number. Although the tools of standard, grand-canonical density functional theory are often used in an ad hoc manner to study closed systems, their formulation directly in the canonical ensemble has so far not been known. In this work, the fundamental theorems underlying classical DFT are revisited and carefully compared in the two ensembles showing that there are only trivial formal differences. The practicality of DFT in the canonical ensemble is then illustrated by deriving the exact Helmholtz functional for several systems: the ideal gas, certain restricted geometries in arbitrary numbers of dimensions, and, finally, a system of two hard spheres in one dimension (hard rods) in a small cavity. Some remarkable similarities between the ensembles are apparent even for small systems with the latter showing strong echoes of the famous exact of result of Percus in the grand-canonical ensemble.


Is Small Scale Dairy Farming Dying Out? An In-depth Study.
Animal husbandry plays an important role in the Indian economy. Small scale milk producers contribute 62% of the total milk produced in the country. However, the lives and livelihoods of small dairy farmers are becoming vulnerable in India. This article tried tried to explore the reasons of decrease in small scale dairy farms. Apart from that this article is also find out what were the challenges faced by small dairy farming families and its influence on animal health. A qualitative exploratory study was carried out in the peri-urban area of Hodal, Haryana. Purposive and snowball sampling were employed. Twenty-six in-depth interviews were conducted with current small scale dairy farmers, ex small scale dairy farmers, households, and other stakeholders. Results are presented in the form of core and sub-themes evolved during this process. This study revealed that a small scale dairy farmer is present in peri-urban area, but there is a decrease in small scale dairy farming. The major reason is shrinking fringes, access to cattle provender, the tepid interest of future generation, increased cost of cattle, and cattle health. The study recommends that support (in the form of subsidy) should be provided to small scale dairy farmers for accessing land and provender. Awareness about the importance and scope of small scale dairy farming as a stable career opportunity should be spread among the young generation.


Medical student name tags: identification or obfuscation?
To explore how U.S. medical students doing clinical rotations are physically identified to patients via their name tags, and how patients interpret the educational status conveyed by those name tags. A letter was sent to the dean of students at all 141 medical school campuses in the United States, requesting a photocopy of the name tag distributed to third-year students on clinical rotations. We then surveyed a convenience sample of 100 general medicine outpatients at the Hospital of the University of Pennsylvania and the Philadelphia Veterans Affairs Medical Center and presented them with examples of four ways medical students were identified on name tags we received: "medical student," "student physician," "student doctor," and "MD student." Patients were then asked to rank these, and three other identifiers ("faculty physician," "resident physician," and "house staff"), from least experienced to most experienced. Patients were told that some of the identifiers might denote the same level of experience. Fifty-three percent of the medical school name tags we received identified the medical student as "medical student," 11% as "student," 6% as "student physician," 2% as "student doctor," and 1% as "MD student." Four percent of name tags had only the student's name, and 18% had only the student's name and university affiliation. Patients thought that the four student descriptors ("medical student," "student physician," "student doctor," and "MD student") on medical student name tags indicated less experience than the other three descriptors. However, of the four student descriptors, patients thought "medical student" indicated less experience than the other three (p < .0001). There is great variation in how medical schools identify medical students on the name tags used during their clinical rotations. These different ways of identifying medical students are not interpreted as being identical to many patients.


Ecological consequences of bacterioplankton lifestyles: changes in concepts are needed.
In recent years, microbial ecology has developed from a peripheral discipline into a central field of microbiology. This change in state and perception is mainly driven by a rapid development of methods applied in the manifold fields related to microbial ecology. In biogeochemistry, for example, the use of high-resolution techniques such as FT-ICR-MS (Fourier transform ion cyclotron mass spectroscopy) has uncovered an enormous diversity and complexity of natural organic matter produced or degraded microbially either in dissolved or particulate forms. On the other hand, the introduction of high-throughput sequencing methods, such as 454 pyrosequencing, in combination with advances in bioinformatics allows for studying the bacterial diversity in natural samples circumventing cultivation dependent approaches. These new molecular tools enable in depth studies on single-cell genomes, distinct populations or even metacommunities. In combination with metatranscriptome and proteome studies it is for the first time possible to simultaneously unravel the structure and function of complex communities in situ. These technique-derived findings have, on the one hand, dramatically increased our knowledge on the vast diversity and complexity of bacterial habitats and, on the other hand, on phylogentic diversity and physiological responses of natural bacterial communities to their environment. However, until now microbial ecology is lacking an ecologically relevant species definition and useful tools for the identification of ecologically coherent taxa. Studies on intra- and interspecies interactions even with higher organisms demonstrate that bacteria can rapidly adapt to temporal and spatial changes in their environment. Aquatic bacteria have optimized and dramatically expanded their living space by efficient exploitation of organic matter point sources such as particles/aggregates and higher organisms. Although it is evident that particles/aggregates and organisms such as phytoplankton are 'hotspots' for microbial growth and transformation processes, it has not affected sampling strategies of aquatic microbial ecologists, who often focus solely on the free-living bacterial fractions and a priori exclude higher organisms by non-representative water sampling. Therefore, aquatic microbial ecologists have largely overlooked the fact that many aquatic bacteria may possess a complex lifestyle and frequently alternate between a free-living and a surface-associated stage. Here, I propose that modern concepts in aquatic microbial ecology should take into account the high chemical diversity and spatio-temporal variability of the bacterial environment. Interactions of aquatic bacteria with surfaces including living organisms are the key to understanding their physiological adaptations and population dynamics, as well as their contribution to biogeochemical cycles. New sampling strategies and theoretical concepts are needed in aquatic microbial ecology to access the whole spectrum of bacterial lifestyles and their ecological and evolutionary consequences.


Cyclooxygenase-1 is a potential target for prevention and treatment of ovarian epithelial cancer.
The precise genetic and molecular defects underlying epithelial ovarian cancer (EOC) remain largely unknown, and treatment options for patients with advanced disease are limited. Cyclooxygenases (COX-1 and COX-2) catalyze the conversion of arachidonic acid to prostaglandins. Whereas overwhelming evidence suggests a role for COX-2 in a variety of cancers, the contribution of COX-1 remains much less explored. The expression status of COX isoforms in ovarian cancers also remains confusing. We have previously shown that human epithelial ovarian tumors have increased levels of COX-1 but not COX-2. To more carefully examine the role of COXs in ovarian cancer, we used a mouse model of EOC in which genetic and oncogenic modifications were experimentally engineered into ovarian surface epithelial cells (OSE) thought to be the cells of origin for human EOC. These OSE cells produce tumors when allografted into host mice. Using multiple approaches, we observed that OSE cells and the tumors comprised of these cells express high levels of COX-1 but not COX-2. Prostacyclin (PGI(2)) is the major prostaglandin generated downstream of COX-1 in these cells, and SC-560, a COX-1-selective inhibitor, dramatically inhibits PGI(2) production. More importantly, SC-560 reduced the growth of tumors when OSE cells were allografted in nude female mice. In contrast, the COX-2-selective inhibitor celecoxib had little effect on tumor growth. The growth inhibitory effects of SC-560 result from reduced cell proliferation and/or accelerated apoptosis. Our results imply COX-1 as a target for the prevention and/or treatment of EOC.


Comparison of interval timing behaviour in mice following dorsal or ventral hippocampal lesions with mice having δ-opioid receptor gene deletion.
Mice with cytotoxic lesions of the dorsal hippocampus (DH) underestimated 15 s and 45 s target durations in a bi-peak procedure as evidenced by proportional leftward shifts of the peak functions that emerged during training as a result of decreases in both 'start' and 'stop' times. In contrast, mice with lesions of the ventral hippocampus (VH) displayed rightward shifts that were immediately present and were largely limited to increases in the 'stop' time for the 45 s target duration. Moreover, the effects of the DH lesions were congruent with the scalar property of interval timing in that the 15 s and 45 s functions superimposed when plotted on a relative timescale, whereas the effects of the VH lesions violated the scalar property. Mice with DH lesions also showed enhanced reversal learning in comparison to control and VH lesioned mice. These results are compared with the timing distortions observed in mice lacking δ-opioid receptors (Oprd1(-/-)) which were similar to mice with DH lesions. Taken together, these results suggest a balance between hippocampal-striatal interactions for interval timing and demonstrate possible functional dissociations along the septotemporal axis of the hippocampus in terms of motivation, timed response thresholds and encoding in temporal memory.


[Prenatal diagnosis of tricuspid atresia].
Tricuspid atresia is the third most common cyanotic cardiac malformation, seen in 1 per cent of children with congenital heart disease. It occurs in 4-5 per cent of congenital heart defects diagnosed prenatally, this difference is a consequence of a high percentage of intrauterine death these severely ill fetuses. Initial surgical treatment is palliation, usually with aortopulmonary shunt. Definitive treatment is the Fontan operation, when the systemic venous return is connected directly to the pulmonary tree. Five-year survival for liveborn patients is 50, but for prenatally diagnosed fetuses only 20%. In Hungary there is only a few survivor. Authors have diagnosed 20 tricuspid atresias during a five-year period by fetal echocardiography. In two cases the postnatal findings were: normal tricuspid valves, univentricular atrio-ventricular connection and stenosis of the pulmonary artery, in one case dysplastic tricuspid valves, hypoplastic right ventricle and stenosis of the pulmonary artery. Authors summarise their experiences with prenatal echocardiography of tricuspid atresia and describe characteristic signs could be found by routine ultrasound screening of this severe cardiac malformation.


Whole exome sequencing identifies novel pathogenic variants in TGM1 and ALOX12B in patients with hereditary ichthyosis.
Hereditary ichthyosis is a clinically and genetically heterogeneous disorder associated with more than 50 genes with TGM1, ALOX12B, and ALOXE3 being the most prevalent. Establishing an accurate diagnosis is important for effective genetic counseling and optimal patient management. We studied the diagnostic value of whole exome sequencing (WES) in a small case series with hereditary ichthyosis. During a 1-year period, index cases of 5 unrelated families clinically diagnosed with hereditary ichthyosis went through WES, followed by extensive segregation analysis. Prenatal diagnosis (PND) was conducted where indicated. We identified 4 homozygous variants-2 in TGM1 (c.655A > G and c.797A > G) and 2 in ALOX12B (c.527 + 2 T > G and c.1654G > T)-alongside a heterozygous variant in TGM1 (c.428G > A) in 5 families. The variants were all pathogenic/likely pathogenic according to the ACMG classification and segregation analysis, except for c.797A > G in TGM1 which remained a variant of unknown clinical significance. Four variants were novel. All families were referred either during pregnancy or before reproductive planning; 4 benefited from WES as it identified the mutation in the probands and enabled carrier detection in at-risk relatives; PND was conducted in 2 families. Our findings further support WES is a powerful tool for the comprehensive, accurate, and rapid molecular diagnosis of hereditary ichthyosis and can offer opportunities for reproductive planning, carrier screening and prenatal diagnosis to at-risk families.


Induced gamma band activity from EEG as a possible index of training-related brain plasticity in motor tasks.
The aim of this study was proposing gamma band activity (GBA) as an index of training-related brain plasticity in the motor cortex. Sixteen controls underwent an experimental session where electroencephalography (EEG) activity was recorded at baseline (resting) and during a motor task (hand movements). GBA was obtained from the EEG data at baseline and during the task. Index of plasticity (IP) was defined as the relationship between GBA at the end of the motor task (GBAM_FIN), divided by GBA at the beginning of the task (GBAM_INI) for movements of both hands. There was a significant increase in GBA at the end of the task, compared to the initial GBA for the motor task (GBAM_FIN > GBAM_INI). No differences were found at baseline (GBAB_FIN ≈ GBAB_INI). Individual IP values had a positive (r = 0.624) and significant correlation with subject's handedness. Due to plastic changes, GBA could indirectly but objectively reveal changes in cerebral activity related to physical training. This method could be used as a future diagnostic test in the follow-up of patients undergoing rehabilitation. It could also have potential applications in the fields of sports medicine.


Endoscopic Ultrasound-Guided Management of Pancreatic Fluid Collections: Update and Review of the Literature.
Severe acute pancreatitis is often complicated by the development of pancreatic fluid collections (PFCs), which may be associated with significant morbidity and mortality. It is crucial to accurately classify these collections as a pseudocyst or walled-off necrosis (WON) given significant differences in outcomes and management. Interventions for PFCs have increasingly shifted to less invasive strategies, with endoscopic ultrasound (EUS)-guided methods being shown to be safer and equally effective as more invasive surgical techniques. In recent years, many new developments have improved the safety and efficacy of EUS-guided interventions, such as the introduction of lumen-apposing metal stents (LAMS), direct endoscopic necrosectomy (DEN) and multiple other adjunctive techniques. Despite these developments, treatment of PFCs, and infected WON in particular, continues to be associated with significant morbidity and mortality. In this article, we discuss the EUS-guided management of PFCs while reviewing the latest developments and controversies in the field. We end by summarizing our own approach to managing PFCs.


Benefits of Exercise on the Executive Functions in People with Parkinson Disease: A Controlled Clinical Trial.
We have made a 3-arm trial (group vs. individual exercise vs. no treatment) to test the effects of a 6-month exercise program upon the executive functions in participants with Parkinson disease. Twenty-four subjects were randomly allocated in 3 groups and undertook individualized exercises (G1, n = 8), group exercises (G2, n = 8), or monitoring (G3, n = 8). Executive functions were evaluated by means of the Wisconsin card sorting test and the Raven colored matrices, both assessed at the beginning of the program and after 6 months. The statistical analyses consisted of the application of repeated measurement tests, with a significant level of 5%. The findings showed similar behavior of groups in terms of the Wisconsin card sorting test (P = 0.792), reporting no benefit of the program on such instrument. Differently, Raven colored matrices evidenced a significant benefit provided by the intervention (P = 0.032). Compared with the control group, individuals from G1 had a substantial improvement on executive functions (P = 0.031) and from G2 had a trend of significance (P = 0.072). Findings of this study show that 6 months of exercise improved some aspects of executive functions when compared with control peers. Individual therapy seems to have a more prominent improvement than group therapy.


The changing face of hemostasis testing in modern laboratories: consolidation, automation, and beyond.
The reality of laboratory diagnostics as a whole, and hemostasis testing in particular, is evolving under new paradigms of efficiency. The driving forces of health care and laboratory diagnostics in the third millennium are mainly represented by macro- and microeconomics. In a world with limited resources, shattered by an unprecedented economic crisis, laboratory diagnostics is undergoing a substantial reorganization, with emergence of new models under the imperative of terms, such as bedside testing, consolidation, and networking. The paradigms under which these changes are being developed include a variety of environment, preanalytical, technological, professional, and health-care aspects. The maintenance of continued quality is indeed the major challenge to be faced in the foreseeable future. In fact, some challenges prepotently emerge during a consolidation process, which basically involve delayed testing, centrifugation, transportation, and stability of the specimens, as well as the potential mismatch of sample matrix. This article is aimed to provide an overview of the current economic scenario of laboratory diagnostics and discuss the changing face of hemostasis testing in modern laboratories, providing a synthetic overview about potential drawbacks of actualized solutions.


Influence of the molecular weight and size distribution of PSS on mixed ionic-electronic transport in PEDOT:PSS.
The commercially available polyelectrolyte complex poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) is ubiquitous in organic and hybrid electronics. As such, it has often been used as a benchmark material for fundamental studies and the development of new electronic devices. Yet, most studies on PEDOT:PSS have focused on its electronic conductivity in dry environments, with less consideration given to its ion transport, coupled ionic-electronic transport, and charge storage properties in aqueous environments. These properties are essential for applications in bioelectronics (sensors, actuators), charge storage devices, and electrochromic displays. Importantly, past studies on mixed ionic-electronic transport in PEDOT:PSS neglected to consider how the molecular structure of PSS affects mixed ionic-electronic transport. Herein, we therefore investigated the effect of the molecular weight and size distribution of PSS on the electronic properties and morphology of PEDOT:PSS both in dry and aqueous environments, and overall performance in organic electrochemical transistors (OECTs). Using reversible addition-fragmentation chain transfer (RAFT) polymerization with two different chain transfer agents, six PSS samples with monomodal, narrow (Đ = 1.1) and broad (Đ = 1.7) size distributions and varying molecular weights were synthesized and used as matrices for PEDOT. We found that using higher molecular weight of PSS (M n = 145 kg mol-1) and broad dispersity led to OECTs with the highest transconductance (up to 16 mS) and [μC * ] values (~140 F·cm-1V-1s-1) in PEDOT:PSS, despite having a lower volumetric capacitance (C * = 35 ± 4 F cm-3). The differences were best explained by studying the microstructure of the films by atomic force microscopy (AFM). We found that heterogeneities in the PEDOT:PSS films (interconnected and large PEDOT- and PSS-rich domains) obtained from high molecular weight and high dispersity PSS led to higher charge mobility (μ OECT ~ 4 cm2V-1s-1) and hence transconductance. These studies highlight the importance of considering molecular weight and size distribution in organic mixed ionic-electronic conductor, and could pave the way to designing high performance organic electronics for biological interfaces.


Prognostic Value of Geriatric Conditions Beyond Age After Acute Coronary Syndrome.
The aim of the present study was to investigate the prognostic value of geriatric conditions beyond age after acute coronary syndrome. This was a prospective cohort design including 342 patients (from October 1, 2010, to February 1, 2012) hospitalized for acute coronary syndrome, older than 65 years, in whom 5 geriatric conditions were evaluated at discharge: frailty (Fried and Green scales), comorbidity (Charlson and simple comorbidity indexes), cognitive impairment (Pfeiffer test), physical disability (Barthel index), and instrumental disability (Lawton-Brody scale). The primary end point was all-cause mortality. The median follow-up for the entire population was 4.7 years (range, 3-2178 days). A total of 156 patients (46%) died. Among the geriatric conditions, frailty (Green score, per point; hazard ratio, 1.11; 95% CI, 1.02-1.20; P=.01) and comorbidity (Charlson index, per point; hazard ratio, 1.18; 95% CI, 1.0-1.40; P=.05) were the independent predictors. The introduction of age in a basic model using well-established prognostic clinical variables resulted in an increase in discrimination accuracy (C-statistic=.716-.744; P=.05), though the addition of frailty and comorbidity provided a nonsignificant further increase (C-statistic=.759; P=.36). Likewise, the addition of age to the clinical model led to a significant risk reclassification (continuous net reclassification improvement, 0.46; 95% CI, 0.21-0.67; and integrated discrimination improvement, 0.04; 95% CI, 0.01-0.09). However, the addition of frailty and comorbidity provided a further significant risk reclassification in comparison to the clinical model with age (continuous net reclassification improvement, 0.40; 95% CI, 0.16-0.65; and integrated discrimination improvement, 0.04; 95% CI, 0.01-0.10). In conclusion, frailty and comorbidity are mortality predictors that significantly reclassify risk beyond age after acute coronary syndrome.


Elemental Mapping of Human Malignant Mesothelioma Tissue Samples Using High-Speed LA-ICP-TOFMS Imaging.
This is the first report of the use of laser ablation-inductively coupled plasma time-of-flight mass spectrometry (LA-ICP-TOFMS) to analyze human malignant pleural mesothelioma (MPM) samples at the cellular level. MPM is an aggressive, incurable cancer associated with asbestos exposure, with a long latency and poor overall survival. Following careful optimization of the laser fluence, the simultaneous ablation of soft biological tissue and hard mineral fibers was possible, allowing the spatial detection of elements such as Si, Mg, Ca, and Fe, which are also present in the glass substrate. A low-dispersion LA setup was employed, which provided the high spatial resolution necessary to identify the asbestos fibers and fiber fragments in the tissue and to characterize the metallome at the cellular level (a pixel size of 2 μm), with a high speed (at 250 Hz). The multielement LA-ICP-TOFMS imaging approach enabled (i) the detection of asbestos fibers/mineral impurities within the MPM tissue samples of patients, (ii) the visualization of the tissue structure with the endogenous elemental pattern at high spatial resolution, and (iii) obtaining insights into the metallome of MPM patients with different pathologies in a single analysis run. Asbestos and other mineral fibers were detected in the lung and pleura tissue of MPM patients, respectively, based on their multielement pattern (Si, Mg, Ca, Fe, and Sr). Interestingly, strontium was detected in asbestos fibers, suggesting a link between this potential toxic element and MPM pathogenesis. Furthermore, monitoring the metallome around the talc deposit regions (characterized by elevated levels of Al, Mg, and Si) revealed significant tissue damage and inflammation caused by talc pleurodesis. LA-ICP-TOFMS results correlated to Perls' Prussian blue and histological staining of the corresponding serial sections. Ultimately, the ultra-high-speed and high-spatial-resolution capabilities of this novel LA-ICP-TOFMS setup may become an important clinical tool for simultaneous asbestos detection, metallome monitoring, and biomarker identification.


Spectral, Compositional, and Physical Properties of the Upper Murray Formation and Vera Rubin Ridge, Gale Crater, Mars.
During 2018 and 2019, the Mars Science Laboratory Curiosity rover investigated the chemistry, morphology, and stratigraphy of Vera Rubin ridge (VRR). Using orbital data from the Compact Reconnaissance Imaging Spectrometer for Mars, scientists attributed the strong 860 nm signal associated with VRR to the presence of red crystalline hematite. However, Mastcam multispectral data and CheMin X-ray diffraction (XRD) measurements show that the depth of the 860 nm absorption is negatively correlated with the abundance of red crystalline hematite, suggesting that other mineralogical or physical parameters are also controlling the 860 nm absorption. Here, we examine Mastcam and ChemCam passive reflectance spectra from VRR and other locations to link the depth, position, and presence or absence of iron-related mineralogic absorption features to the XRD-derived rock mineralogy. Correlating CheMin mineralogy to spectral parameters showed that the ~860 nm absorption has a strong positive correlation with the abundance of ferric phyllosilicates. New laboratory reflectance measurements of powdered mineral mixtures can reproduce trends found in Gale crater. We hypothesize that variations in the 860 nm absorption feature in Mastcam and ChemCam observations of VRR materials are a result of three factors: (1) variations in ferric phyllosilicate abundance due to its ~800-1,000 nm absorption; (2) variations in clinopyroxene abundance because of its band maximum at ~860 nm; and (3) the presence of red crystalline hematite because of its absorption centered at 860 nm. We also show that relatively small changes in Ca-sulfate abundance is one potential cause of the erosional resistance and geomorphic expression of VRR.


[Tyrosine nitration as regulatory post-translational modification of proteins].
Review highlights new pathways of signal transduction from nitric oxide (NO) that is a recognized secondary messenger in regulatory cascades of phylogenetically distant species. Indirect (via Ca2+ and cGMP) and direct (protein S-nitrosylation and tyrosine nitration) pathways of NO signal transduction are presented. S-nitrosyation as new paradigm in signal transduction and protein functions regulations is discussed. The importance of animal and plant protein tyrosine nitration in vivo and the potential regulatory significance of this posttranslational modification are emphasized. Also review describes tree mechanisms of protein tyrosine nitration: via peroxynitrite, peroxydase and haem-peroxidase. Particular attention is paid to cytoskeleton proteins tyrosine nitration, particularly tubulines, because microtubules are involved into modulation of signal transduction from various messengers.


Eating less or more - Mindset induced changes in neural correlates of pre-meal planning.
Obesity develops due to an imbalance between energy intake and expenditure. Besides the decision about what to eat, daily energy intake might be even more dependent on the decision about the portion size to be consumed. For decisions between different foods, attentional focus is considered to play a key role in the choice selection. In the current study, we investigated the attentional modulation of portion size selection during pre-meal planning. We designed a functional magnetic resonance task in which healthy participants were directed to adopt different mindsets while selecting their portion size for lunch. Compared with a free choice condition, participants reduced their portion sizes when considering eating for health or pleasure, which was accompanied by increased activity in left prefrontal cortex and left orbitofrontal cortex, respectively. When planning to be full until dinner, participants selected larger portion sizes and showed a trend for increased activity in left insula. These results provide first evidence that also the cognitive process of pre-meal planning is influenced by the attentional focus at the time of choice, which could provide an opportunity for influencing the control of meal size selection by mindset manipulation.


Longitudinal outcomes of radiofrequency ablation versus surveillance endoscopy for Barrett's esophagus with low-grade dysplasia.
Radiofrequency ablation of Barrett's esophagus with low-grade dysplasia is recommended in recent American College of Gastroenterology guidelines, with endoscopic surveillance considered a reasonable alternative. Few studies have directly compared outcomes of radiofrequency ablation to surveillance and those that have are limited by short duration of follow-up. This study aims to compare the long-term effectiveness of radiofrequency ablation versus endoscopic surveillance in a large, longitudinal cohort of patients with Barrett's esophagus, and low-grade dysplasia.We conducted a retrospective analysis of patients with confirmed low-grade dysplasia at a single academic medical center from 1991 to 2014. Patients progressing to high-grade dysplasia or esophageal adenocarcinoma within one year of index LGD endoscopy were defined as missed dysplasia and excluded. Risk factors for progression were assessed via Cox proportional hazards model. Comparison of progression risk was conducted using a Kaplan-Meier analysis. Subset analyses were conducted to examine the effect of reintroducing early progressors and excluding patients diagnosed prior to the advent of ablative therapy. Of 173 total patients, 79 (45.7%) underwent radiofrequency ablation while 94 (54.3%) were untreated, with median follow up of 90 months. Seven (8.9%) patients progressed to high-grade dysplasia or adenocarcinoma despite ablation, compared with 14 (14.9%) undergoing surveillance (P = 0.44). This effect was preserved when patients diagnosed prior to the introduction of radiofrequency ablation were excluded (8.9% vs 13%, P = 0.68). Reintroduction of patients progressing within the first year of follow-up resulted in a trend toward significance for ablation versus surveillance (11.1% vs 23.8%, P = 0.053).In conclusion, progression to high-grade dysplasia or adenocarcinoma was not significantly reduced in the radiofrequency ablation cohort when compared to surveillance. Despite recent studies suggesting the superiority of radiofrequency ablation in reducing progression, diligent endoscopic surveillance may provide similar long-term outcomes.


Fetal cartilage xylosyltransferase activity and skeletal growth in sheep.
The activity of UDP-D-xylose:proteoglycan core protein beta-D-xylosyltransferase (EC 220.127.116.11), the enzyme that catalyzes the initiation of the polysaccharide chain linkage to the core protein of proteoglycans, was measured in costal cartilage from 20 fetal sheep of 65-138 days gestation. Activity of the enzyme was estimated from the transfer of [14C]xylose from UDP-[14C]xylose to silk as the acceptor protein. The specific activity decreased approximately 10-fold and was found to be highly correlated with the decremental rate of growth in length of the fetal vertebral column. These observations, together with the known gestational decrease in the in vitro rate of uptake of radiolabeled sulfate by ovine fetal cartilage, a subsequent step in proteoglycan synthesis, support the hypothesis that normal fetal skeletal growth is dependent during the last one-half of gestation on the activity of xylosyltransferase in cartilage.


HIV-1, HCV and alcohol in the CNS: potential interactions and effects on neuroinflammation.
Approximately 25% of the HIV-1 positive population is also infected with HCV. The effects of alcohol on HIV-1 or HCV infection have been a research topic of interest due to the high prevalence of alcohol use in these infected patient populations. Although it has long been known that HIV-1 infects the brain, it has only been a little more than a decade since HCV infection of the CNS has been characterized. Both viruses are capable of infecting and replicating in microglia and increasing the expression of proinflammatory cytokines and chemokines, including IL-6 and IL-8. Investigations focusing on the effects of HIV-1, HCV or alcohol on neuroinflammation have demonstrated that these agents are capable of acting through overlapping signaling pathways, including MAPK signaling molecules. In addition, HIV-1, HCV and alcohol have been demonstrated to increase permeability of the blood-brain barrier. Patients infected with either HIV-1 or HCV, or those who use alcohol, exhibit metabolic abnormalities in the CNS that result in altered levels of n-acetyl aspartate, choline and creatine in various regions of the brain. Treatment of HIV/HCV co-infection in alcohol users is complicated by drug-drug interactions, as well as the effects of alcohol on drug metabolism. The drug-drug interactions between the antiretrovirals and the antivirals, as well as the effects of alcohol on drug metabolism, complicate existing models of CNS penetration, making it difficult to assess the efficacy of treatment on CNS infection.


Exact (spiral + circles) scan region-of-interest cone beam reconstruction via backprojection.
We present a (spiral + circles) scan cone beam reconstruction algorithm in which image reconstruction proceeds via backprojection in the object space. In principle, the algorithm can reconstruct sectional region-of-interest (ROI) in a long object. The approach is a generalization of the cone beam backprojection technique developed by Kudo and Saito in two aspects: the resource-demanding normalization step in the Kudo and Saito's algorithm is eliminated through the technique of data combination that we published earlier, and the elimination of the restriction that the detector be big enough to capture the entire cone beam projection of the ROI. Restricting the projection data to the appropriate angular range required by data combination can be accomplished by a masking process. Because of the simplification resulting from the elimination of the normalization step, the most time-consuming operations of the algorithm can be approximated by the efficient step of line-by-line ramp filtering the cone beam image in the direction of the scan path, plus a correction image. The correction image, which can be computed exactly, is needed because data combination is not properly matched at the mask boundary when ramp filtering is involved. Empirical two-dimensional (2-D) point spread function (PSF) is developed to improve matching with the correction image which is computed with finite samplings. The use of transition region to further improve matching is introduced. The results of testing the algorithm on simulated phantoms are presented.


Mitochondrial cytochrome deficiency presenting as a myopathy with hypotonia, external ophthalmoplegia, and lactic acidosis in an infant and as fatal hepatopathy in a second cousin.
Fatal infantile mitochondrial myopathy with lactic acidosis, morphologically abnormal mitochondria, deficient cytochromes aa3 and b, and a Fanconi-like aminoaciduria has been described. We report two infants, second cousins, with a similar fatal mitochondrial disorder, the cytochrome deficiency limited to skeletal muscle in one child and to liver in the other. The first child at 3 months of age had weight loss, hypotonia, external ophthalmoplegia, and a severe lactic acidosis with a high lactate/pyruvate ratio. Electron microscopy of muscle showed marked proliferation of enlarged mitochondria, many containing concentric rings of cristae. In skeletal muscle mitochondria, cytochromes aa3 and b were not detectable but cytochrome cc was found to be normal by spectroscopy. Cytochrome c oxidase activity was less than 1% of normal. Mitochondria from kidney, liver, heart, lung, and brain examined postmortem had normal cytochromes and preserved cytochrome c oxidase activity. The second cousin at 5 months of age had weight loss and hepatomegaly but no systemic lactic acidosis. Liver biopsy showed hepatocytes packed with enlarged mitochondria. The liver mitochondria showed deficient cytochromes aa3 and b postmortem, and cytochrome c oxidase activity was less than 10% of normal. Kidney mitochondria had normal cytochromes. Muscles was not studied. The mitochondrial abnormality in the two cousins presumably is related. Unexplained are the mode of genetic transmission or environmental exposure and the apparent involvement of a single different organ in each child.


Oral carbohydrate loading with 18% carbohydrate beverage alleviates insulin resistance.
Preoperative 12.6% oral carbohydrate loading is an element of the Enhanced Recovery After Surgery (ERAS) protocol aimed at alleviating postoperative insulin resistance; however, in Japan, beverages with 18% carbohydrate content are generally used for preoperative carbohydrate loading. We investigated the effect of 18% carbohydrate loading on alleviating insulin resistance. Six healthy volunteers participated in this crossover-randomized study and were segregated into 2 groups: volunteers in the carbohydrate-loading group (group A) who fasted from after 9 pm and ingested 375 mL of a beverage containing 18% carbohydrate (ArginaidWaterTM; Nestle, Tokyo, Japan) between 9 pm and 12 pm, and 250 mL of the same liquid at 6:30 am. Volunteers in control group (group B) drank only water. At 8:30 am, a hyperinsulinemic normoglycemic clamp was initiated. Glucose infusion rate (GIR) and levels of ketone bodies and cytokines (IL-1β, IL-6, and TNF-α) before clamping were evaluated. p<0.05 was considered statistically significant. Levels of blood glucose, insulin, and cytokines at the start of the clamp were similar in both the groups. The GIR in group A was significantly higher than that in group B (11.5±2.4 vs 6.2±2.2 mg/kg/min, p=0.005), while blood ketone body levels were significantly lower in group A (22±4 vs 124±119 μmol/L, p=0.04). Preoperative 18% carbohydrate loading could prevent the decrease in insulin sensitivity and suppress catabolism in healthy volunteers. Thus, carbohydrate loading with a beverage with 18% carbohydrate content might contribute to improvements in perioperative management.


'Dicty dynamics': Dictyostelium motility as persistent random motion.
We model the motility of Dictyostelium cells in a systematic data-driven manner. We deduce a minimal dynamical model that reproduces the statistical features of experimental trajectories. These are trajectories of the centroid of the cell perimeter, which is more sensitive to pseudopod activity than the usual tracking by centroid or nucleus. Our data account for cell individuality and dictate a model that extends the cell-type specific models recently derived for mammalian cells. Two generalized Langevin equations model stochastic periodic pseudopod motion parallel and orthogonal to the amoeba's direction of motion. This motion propels the amoeba with a random periodic left-right waddle in a direction that has a long persistence time. The model fully accounts for the statistics of the experimental trajectories, including velocity power spectra and auto-correlations, non-Gaussian velocity distributions, and multiplicative noise. Thus, we find neither need nor place in our data for an interpretation in terms of anomalous diffusion. The model faithfully captures cell individuality as different parameter values in the model, and serves as a basis for integrating the local mechanics of cell motion with our observed long-term behavior.


[Obesity and diseases of digestive organs].
Obesity is non-infectious pandemic. Its association with cardiovascular pathology is especially widely discussed, but an overweight patient is actually polymorbid. An increase of body mass provides a pathogenetic basis for many diseases including those of digestive system This review deals with pathogenesis, clinical features, and treatment of gastroesophageal reflux disease, cholelithiasis and non-alcoholic fatty liver disease in obese patients. This pathology and its aggravation result from such pathophysiological processes as a rise in intra-abdominal pressure, excess adipokine, cholesterol and free fatty acid synthesis, activation of lipid peroxidation. Gastroesophageal reflux disease in obese patients has an atypical clinical course characterized by discrepancy between clinical, endoscopic and morphological features in oesophagus and frequent formation of Barrett's oesophagus. Cholelethiasis in obesity is fraught with further progress of the disease after prescription of low-fat diet. The risk of calculi formation can be reduced by prescription of ursodeoxycholic acid that produces both litholytic and hypolipidemic effects. Treatment of non-alcoholic fatty liver disease requires combined therapy with statins, insulin sensitizers, hepatoprotectors and adequate physical activity. Sustained remission of diseases of digestive organs is impossible without correction of body mass and their pharmacotherapy requires increasing doses of medicines and duration of their administration.


Active role of the predecidual-like zone in endometrial shedding in a mouse menstrual-like model.
Cyclic shedding of the endometrium is unique to menstruating species. The status of the decidua in mouse menstrual-like models seems to differ from that of the predecidua in humans before endometrial breakdown. The aim of this study was to determine how this difference in decidual status is related to endometrial breakdown. A mouse menstrual-like model was generated by pharmacological progesterone withdrawal. Histomorphological analysis and reticular fiber staining were used to evaluate endometrial status. In situ zymography was used to determine the localization of active collagenase and gelatinase. The functional endometrial layer containing the mature decidual-like zone (MDZ) and predecidual-like zone (PZ) underwent breakdown. The reticular fibers underwent disruption and fragmentation and became loose or disappeared at 12 h in the PZ, where active collagenase and gelatinase were limited. The reticular fibers were visibly reduced at 24 h in the MDZ, where active collagenase was detected. A few reticular fibers remained; however, the functional layer had sloughed into the lumen of the uterus. The results showed that reticular fibers of the PZ are actively degraded during endometrial shedding.


Variables associated with obesity among African-American women in Omaha.
Obesity is a health disparity related to environmental, social, and physical health issues, including ethnicity, education, and gender. The purpose of this study was to examine the relationship among obesity, age, education, and socioeconomic status and the relationship between obesity and depression among African-American women living in Omaha, Nebraska. A convenience sample of 378 African-American women completed the African-American Female Health Survey, which included the Center for Epidemiologic Studies Depression scale. Body mass index (BMI) was used to measure obesity. Results indicated that 87% of the women were overweight; mean BMI was 32.78 with high cardiovascular disease risks. There was a statistically significant and positive relationship between depression and BMI (r = .201, p < .01). Occupational therapists may provide primary, secondary, and tertiary intervention through culturally relevant and meaningful health education programs.


Double-blind, proof-of-concept (POC) trial of Low-Field Magnetic Stimulation (LFMS) augmentation of antidepressant therapy in treatment-resistant depression (TRD).
Low-Field Magnetic Stimulation (LFMS) is a novel, non-invasive, sub-threshold neuromodulation technique, shown in preliminary studies to have immediate mood elevating effects in both unipolar and bipolar depressed patients. We aimed to assess the antidepressant augmentation effects at 48 h of LFMS administered on two consecutive days compared to sham treatment in treatment resistant depression (TRD) subjects, using the Sequential Parallel Comparison Design (SPCD). Eighty-four eligible subjects with TRD were randomly assigned to double-blind treatment with LFMS 20 min/day for four days, sham treatment 20 min/day for four days, or sham treatment 20 min/day for 2 days followed by LFMS treatment 20 min/day for two days, using the pre-randomization version of the SPCD (randomization 1:1:1). The SPCD analyses used a repeated measures linear modeling approach with maximum likelihood estimation to use all available data, and using a 60-40 weighting of Stage 1 vs. 2 responses, with the primary outcome being measured after 2 and 4 days. Both primary and secondary outcome measures consistently showed no differences between LFMS-treated patients and those treated with sham, with the exception of a slight, non-significantly greater improvement than sham in the visual analogue scale (VAS) sad mood on LFMS-treated patients. LFMS treatment was relatively well tolerated. We did not observe a significantly greater, rapid efficacy of LFMS compared to sham therapy. Future studies need to examine the possible therapeutic effects of more intensive forms of LFMS, as other forms of neurostimulation typically require longer duration of exposure.


Characterization and distribution of repetitive elements in association with genes in the human genome.
Repetitive elements constitute more than 50% of the human genome. Recent studies implied that the complexity of living organisms is not just a direct outcome of a number of coding sequences; the repetitive elements, which do not encode proteins, may also play a significant role. Though scattered studies showed that repetitive elements in the regulatory regions of a gene control gene expression, no systematic survey has been done to report the characterization and distribution of various types of these repetitive elements in the human genome. Sequences from 5' and 3' untranslated regions and upstream and downstream of a gene were downloaded from the Ensembl database. The repetitive elements in the neighboring of each gene were identified and classified using cross-matching implemented in the RepeatMasker. The annotation and distribution of distinct classes of repetitive elements associated with individual gene were collected to characterize genes in association with different types of repetitive elements using systems biology program. We identified a total of 1,068,400 repetitive elements which belong to 37-class families and 1235 subclasses that are associated with 33,761 genes and 57,365 transcripts. In addition, we found that the tandem repeats preferentially locate proximal to the transcription start site (TSS) of genes and the major function of these genes are involved in developmental processes. On the other hand, interspersed repetitive elements showed a tendency to be accumulated at distal region from the TSS and the function of interspersed repeat-containing genes took part in the catabolic/metabolic processes. Results from the distribution analysis were collected and used to construct a gene-based repetitive element database (GBRED; http://www.binfo.ncku.edu.tw/GBRED/index.html). A user-friendly web interface was designed to provide the information of repetitive elements associated with any particular gene(s). This is the first study focusing on the gene-associated repetitive elements in the human genome. Our data showed distinct genes associated with different kinds of repetitive element and implied such combination may shape the function of these genes. Aside from the conventional view of these elements in genome evolution, results from this study offer a systemic review to facilitate exploitation of these elements in genome function.


National High Blood Pressure Education Program Working Group report on hypertension and chronic renal failure.
End-stage renal disease attributed to hypertension has increased annually for the last decade and will probably worsen through the year 2000. Patients with diabetic nephropathy and patients with hypertensive renal disease account for most new cases annually. Evidence reveals that all levels of untreated hypertension are associated with potentially declining renal function. Data from the Hypertension Detection and Follow-up Program and other studies show that antihypertensive treatment can prevent progressive renal failure. An ablation model demonstrates glomerular hyperfiltration as a possible mechanism for progressive renal failure. Human data on the renal effects of antihypertensive agents are limited and inconsistent. Despite the limitations, the Working Group on Hypertension and Chronic Renal Failure concludes that controlled hypertension to less than 140/90 mm Hg reduces the incidence of end-stage renal disease. Patients with established renal impairment may benefit from individualized treatment to 130/85 mm Hg or less.


Blood Cultures and Molecular Diagnostics in Intensive Care Units to Diagnose Sepsis: A Bayesian Latent Class Model Analysis.
Confirmation of sepsis by standard blood cultures (STD) is often inconclusive due to slow growth and low positivity. Molecular diagnostics (MOL) are faster and may have higher positivity, but test performance can be inaccurately estimated if STD methods are used as comparators. Bayesian latent class models (LCMs) can evaluate diagnostic methods when there is no "gold standard." Intensive care unit studies that have used LCMs to combine and compare STD and MOL method performance and estimate the prevalence of sepsis have not been described. Results from an ICU sepsis study that used both tests simultaneously were analyzed. Bayesian LCMs combined prior prevalence of sepsis, prior diagnostic characteristics of the two methods, and the study results to estimate the posterior prevalence and diagnostic characteristics. Sensitivity analyses were performed using objective (published studies) and subjective (expert opinion) prior parameters. Positive predictive values (PPVs) of the prevalence of sepsis were estimated for all combinations of test results. The range of posterior estimates was: sepsis prevalence (0.38-0.88), sensitivities (STD: 0.2-0.35, MOL: 0.56-0.86), and specificities (STD: 0.87-0.99, MOL: 0.72-0.95). The PPV (sepsis) of both tests being positive was (0.72-0.99). LCMs combined two imperfect methods to estimate prevalence, PPV, and diagnostic characteristics. The posterior estimates (STD sensitivity < MOL and STD specificity > MOL) seem to reflect the clinical experience appropriately. The high PPV when both methods show positive results can be useful for ruling in disease. Sampath S, Baby J, Krishna B, Dendukuri N, Thomas T. Blood Cultures and Molecular Diagnostics in Intensive Care Units to Diagnose Sepsis: A Bayesian Latent Class Model Analysis. Indian J Crit Care Med 2021;25(12):1402-1407.


Quantification of gold nanoparticle accumulation in tissue by two-photon luminescence microscopy.
Nanomedicine has emerged as a promising strategy to address some of the limitations of traditional biomedical sensing, imaging and therapy modalities. Its applicability and efficacy are, in part, hindered by the difficulty in both controllably delivering nanoparticles to specific regions and accurately monitoring them in tissue. Gold nanoparticles are among the most extensively used inorganic nanoparticles which benefit from high biocompatibility, flexible functionalization, strong and tunable resonant absorption, and production scalability. Moreover, their capability to enhance optical fields at their plasmon resonance enables local boosting of non-linear optical processes, which are otherwise very inefficient. In particular, two-photon induced luminescence (TPL) in gold offers high signal specificity for monitoring gold nanoparticles in a biological environment. In this article, we demonstrate that TPL microscopy provides a robust sub-micron-resolution technique able to quantify accumulated gold nanorods (GNRs) both in cells and in tissues. First, the temporal accumulation of GNRs with two different surface chemistries was measured in 786-O cells during the first 24 hours of incubation, and at different nanoparticle concentrations. Subsequently, GNR accumulation in mice, 6 h and 24 hours after tail vein injection, was quantified by TPL microscopy in biopsied tissue from kidney, spleen, liver and clear cell renal cell carcinoma (ccRCC) tumors, in good agreement with inductively coupled mass spectroscopy. Our data suggest that TPL microscopy stands as a powerful tool to understand and quantify the delivery mechanisms of gold nanoparticles, highly relevant to the development of future theranostic medicines.


Short-term strength training does not change cortical voluntary activation.
The neural mechanisms responsible for strength improvement in the early phase of strength training are unknown. One hypothesis is that strength increases because of increased neural drive to the trained muscles. Here, we used twitch interpolation to assess voluntary activation before and after a 4-wk strength training program. Twelve volunteers performed unilateral strength training for the right wrist abductors (three times per week). Control subjects (n = 11) practiced the same movement without resistance. We assessed voluntary activation of the trained muscles during wrist abduction and extension contractions using twitch interpolation with motor nerve and motor cortical stimulation. Strength training increased wrist abduction maximal voluntary contraction (MVC) force for the trained hand by 11.0% (+/-8.7, P < 0.01). MVC of the untrained wrist was unchanged. There were no significant changes in wrist extension MVC force in either group. During submaximal wrist abduction, but not extension contractions, the average size of the superimposed twitches produced by cortical stimulation was significantly larger after strength training (P < 0.01). Furthermore, the direction of the twitches produced by cortical stimulation during wrist abductions and maximal wrist extension shifted toward abduction (P = 0.04). There were neither significant changes in voluntary activation measured during MVC with motor nerve or motor cortical stimulation nor changes in the amplitude of evoked EMG responses to motor cortical or motor nerve stimulation. Four weeks of strength training produced a small increase in MVC that was specific to the training direction. Although maximal voluntary activation did not change with short-term strength training, the changes in direction and amplitude of cortically evoked twitches suggest that motor cortical stimulation (and presumably volition) can generate motor output more effectively to the trained muscles.


[Action of unithiol on the toxic effect of antitumor preparations].
The effect of unitiol treatment on the toxicity of dactinomycin, 5-fluorouracil, bleomycetin and vincristine was studied in CBA mice. Unitiol treatment was shown to decrease the acute toxicity of dactinomycin and involves a lower loss of body weight. Also, it reduced dactinomycin hemotoxicity which was assessed on the basis of leukocyte count in peripheral blood. Conversely, unitiol potentiated the acute toxic effect of 5-fluorouracil, bleomycetin and vincristine which was matched by body weight loss following treatment with cytostatic drugs. The results point to a wide range of the biological effects of unitiol.


Establishment of liver specific glucokinase gene knockout mice: a new animal model for screening anti-diabetic drugs.
To characterize the liver-specific role of glucokinase in maintaining glucose homeostasis and to create an animal model for diabetes. We performed hepatocyte-specific gene knockout of glucokinase in mice using Cre-loxP gene targeting strategy. First, two directly repeated loxP sequences were inserted to flank the exon 9 and exon 10 of glucokinase in genomic DNA. To achieve this, linearized targeting vector was electroporated into ES cells. Then G418- and Gancyclovir-double-resistant clones were picked and screened by PCR analysis and the positives identified by PCR were confirmed by Southern blot. A targeted clone was selected for microinjection into C57BL/6J blastocysts and implanted into pseudopregnant FVB recipient. Chimeric mice and their offspring were analyzed by Southern blot. Then by intercrossing the Alb-Cre transgenic mice with mice containing a conditional gk allele, we obtained mice with liver-specific glucokinase gene knockout. Among 161 double resistant clones 4 were positive to PCR and Southern blot and only one was used for further experiments. Eventually we generated the liver specific glucokinase knockout mice. These mice showed increased glucose level with age and at the age of 6 weeks fasting blood glucose level was significantly higher than control and they also displayed impaired glucose tolerance. Our studies indicate that hepatic glucokinase plays an important role in glucose homeostasis and its deficiencies contribute to the development of diabetes. The liver glucokinase knockout mouse is an ideal animal model for MODY2, and it also can be applied for screening anti-diabetic drugs.


[Function of early and late components of the blink reflex--study of discharge behavior of single motor units].
The discharge pattern of single motor units in the early (R1) and late (R2) component of the electrically evoked trigemino-facial blink reflex was investigated by means of selective EMG-recording techniques. At low rate stimulation (0,1 Hz) the stimulus threshold of motor unit discharges in R1 was clearly above that in R2. Higher stimulation rates (1 Hz) were associated with an attenuation of motor unit discharges in R2 according to the well known habituation. The same motor units, however, revealed stable discharges in R1 or even signs of facilitation. These differences of motor unit recruitment in the two components indicate that R1 cannot be simply interpreted as a protective reflex like R2. At higher stimulus intensities, the characteristical firing pattern consisted of single discharges in R1 followed by high frequency multi-discharges of the same motor units in R2. This means that the motor unit discharges in R1 do not only evoke a single twitch of the eyelids but initiate a vigorous tetanic contraction with short latency. Thus, R1 yet reveals a protective function shortening the latency of the reflex blink upon stronger stimuli on the side of the affected eye.


Genome wide identification of cotton (Gossypium hirsutum)-encoded microRNA targets against Cotton leaf curl Burewala virus.
Cotton leaf curl Burewala virus (CLCuBV, genus Begomovirus) causes devastating cotton leaf curl disease. Among various known virus controlling strategies, RNAi-mediated one has shown potential to protect host crop plants. Micro(mi) RNAs, are the endogenous small RNAs and play a key role in plant development and stress resistance. In the present study we have identified cotton (Gossypium hirsutum)-encoded miRNAs targeting the CLCuBV. Based on threshold free energy and maximum complementarity scores of host miRNA-viral mRNA target pairs, a number of potential miRNAs were annotated. Among them, ghr-miR168 was selected as the most potent candidate, capable of targeting several vital genes namely C1, C3, C4, V1 and V2 of CLCuBV genome. In addition, ghr-miR395a and ghr-miR395d were observed to target the overlapping transcripts of C1 and C4 genes. We have verified the efficacy of these miRNA targets against CLCuBV following suppression of RNAi-mediated virus control through translational inhibition or cleavage of viral mRNA.


Epidemiology and treatment of post-stroke depression.
Mood depression is a common and serious complication after stroke. According to epidemiological studies, nearly 30% of stroke patients develop depression, either in the early or in the late stages after stroke. Although depression may affect functional recovery and quality of life after stroke, such condition is often ignored. In fact, only a minority of patients is diagnosed and even fewer are treated in the common clinical practice. Moreover, the real benefits of antidepressant (AD) therapy in post-stroke depression have not been fully clarified. In fact, controlled studies on the effectiveness of ADs in post stroke depression (PSD) are relatively few. Today, data available suggest that ADs may be generally effective in improving mood, but guidelines for the optimal treatment and its length are still lacking.


The effect of nurse prescribers on glycaemic control in type 2 diabetes: A systematic review and meta-analysis.
The creation of advanced nursing roles in diabetes management, with specific skills such as nurse prescribing, has resulted in nurses taking on roles that have traditionally been associated with doctors. We aimed to examine the effectiveness of nurse-led clinics, in which nurses were involved in prescribing, on haemoglobin A1c (HbA1c) among people with type 2 diabetes. We systematically searched the literature, Medline, the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE and Allied Health Literature database guide (CINAHL) databases, to identify randomised controlled trials (RCTs) assessing the effect of nurse prescribers on HbA1c. We focused on randomised controlled trials which compared nurse prescriber interventions with usual care in adults aged 18 years or over with a diagnosis of type 2 diabetes. The main outcome measure was change in HbA1c levels. We performed a random effects model meta-analysis to assess the pooled effect size of the intervention. Studies were divided into two groups according to the role of nurses in the intervention. In one group, the nurses supplemented a team, as an add-on to usual care; in the other group, they worked independently, and were compared directly to a doctor. Nine RCTs were identified and included in this study. All studies were from developed countries, with a medium risk of bias and a moderate heterogeneity between studies. In the five RCTs in which nurse prescribers supplemented a team, there was no significant difference in change of HbA1c compared to usual care (-0.34 percentage points; 95% CI: -0.71, 0.02). In the four RCTs in which nurses replaced doctors, the outcomes of nurse prescribers were comparable to those of doctors. No data on adverse events were available. There was no clear evidence of benefit on glycaemic control, when nurses who undertake prescribing work alongside a doctor and other practitioners. However, in those studies in which nurses replaced physicians, the glycaemic control was comparable between nurses and doctors. Therefore, there may be value in providing nurse-led prescribing services where there is limited access to doctor-led services.


Key Program Findings and Insights From the Baby-Friendly Hawaii Project.
Breastfeeding is the optimal method for infant feeding. In the United States, 81.1% of mothers initiate breastfeeding; however, only 44.4% and 22.3% of mothers are exclusively breastfeeding at 3 and 6 months, respectively. Research aim: The Centers for Disease Control and Prevention provides guidance and funding to state health departments to support strategies to improve breastfeeding policies and practices in the hospital, community, and worksite settings. In 2010, the Hawaii State Department of Health received support from the Centers for Disease Control and Prevention to launch the Baby-Friendly Hawaii Project (BFHP) to increase the number of Hawaii hospitals that provide maternity care consistent with the Ten Steps to Successful Breastfeeding and increase the rate of women who remain exclusively breastfeeding throughout their hospital stay. For this article, we examined the BFHP's final evaluation report and Hawaii breastfeeding and maternity care data to identify the role of the BFHP in facilitating improvements in maternity care practices and breastfeeding rates. Since 2010, 52 hospital site visits, 58 trainings, and ongoing technical assistance were administered, and more than 750 staff and health professionals from BFHP hospitals were trained. Hawaii's overall quality composite Maternity Practices in Infant Nutrition and Care score increased from 65 (out of 100) in 2009 to 76 in 2011 and 80 in 2013, and Newborn Screening Data showed an increase in statewide exclusive breastfeeding from 59.7% in 2009 to 77.0% in 2014. Implementation and findings from the BFHP can inform future planning at the state and federal levels on maternity care practices that can improve breastfeeding.


Modulation of contextual fear conditioning by chronic stress in rats is related to individual differences in behavioral reactivity to novelty.
We investigated whether contextual fear conditioning could be related to the behavioral trait of locomotor reactivity to novelty in undisturbed and chronically stressed rats. Fear conditioning was found to be specifically enhanced in low reactive-stressed animals, as compared to low reactive-undisturbed rats. The results suggest that individuals that display low reactivity to novelty are more susceptible to be influenced by stress exposure to subsequently exhibit potentiated contextual fear conditioning.


Occupational Therapy's Commitment to Diversity, Equity, and Inclusion.
The American Occupational Therapy Association's (AOTA's) Vision 2025 conveys a strong commitment to diversity, equity, and inclusion (AOTA, 2019). AOTA affirms the inalienable right of every individual to feel welcomed, valued, a sense of belonging, and respected while accessing and participating in society, regardless of the internal or external factors that make every individual unique. This statement supports efforts to increase diversity, equity, and inclusion within all aspects of occupational therapy, including practice, education, and research, as well as policy development and advocacy.


Phenytoin-induced lymphadenopathy appearing as a nasopharyngeal malignant neoplasm.
A case of phenytoin sodium-induced lymphadenopathy appeared as a nasopharyngeal malignant neoplasm with regional metastases. Cervical lymphadenopathy is a lesser-known drug reaction that is produced by anticonvulsant therapy; under some circumstances, this condition may be confused with head and neck malignant neoplasms. To date, phenytoin-induced nasopharyngeal lymphadenopathy has not previously been reported in the literature. A review of the medical literature provides some interesting facts about the syndrome. A familiarity with this potential complication of anticonvulsant therapy may expedite early diagnosis and appropriate patient treatment.


Low-level laser therapy to the mouse femur enhances the fungicidal response of neutrophils against Paracoccidioides brasiliensis.
Neutrophils (PMN) play a central role in host defense against the neglected fungal infection paracoccidioidomycosis (PCM), which is caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb). PCM is of major importance, especially in Latin America, and its treatment relies on the use of antifungal drugs. However, the course of treatment is lengthy, leading to side effects and even development of fungal resistance. The goal of the study was to use low-level laser therapy (LLLT) to stimulate PMN to fight Pb in vivo. Swiss mice with subcutaneous air pouches were inoculated with a virulent strain of Pb or fungal cell wall components (Zymosan), and then received LLLT (780 nm; 50 mW; 12.5 J/cm2; 30 seconds per point, giving a total energy of 0.5 J per point) on alternate days at two points on each hind leg. The aim was to reach the bone marrow in the femur with light. Non-irradiated animals were used as controls. The number and viability of the PMN that migrated to the inoculation site was assessed, as well as their ability to synthesize proteins, produce reactive oxygen species (ROS) and their fungicidal activity. The highly pure PMN populations obtained after 10 days of infection were also subsequently cultured in the presence of Pb for trials of protein production, evaluation of mitochondrial activity, ROS production and quantification of viable fungi growth. PMN from mice that received LLLT were more active metabolically, had higher fungicidal activity against Pb in vivo and also in vitro. The kinetics of neutrophil protein production also correlated with a more activated state. LLLT may be a safe and non-invasive approach to deal with PCM infection.


Establishment of a reproducible model of chronic-phase chronic myeloid leukemia in NOD/SCID mice using blood-derived mononuclear or CD34+ cells.
An animal model of chronic myeloid leukemia (CML) will help characterize leukemic and normal stem cells and also help evaluate experimental therapies in this disease. We have established a model of CML in the NOD/SCID mouse. Infusion of > or = 4 x 10(7) chronic-phase CML peripheral blood cells results in engraftment levels of > or = 1% in the bone marrow (BM) of 84% of mice. Engraftment of the spleen was seen in 60% of mice with BM engraftment. Intraperitoneal injection of recombinant stem cell factor produced a higher level of leukemic engraftment without increasing Philadelphia-negative engraftment. Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor did not increase the level of leukemic or residual normal engraftment. Assessment of differential engraftment of normal and leukemic cells by fluorescence in situ hybridization analysis with bcr and abl probes showed that a median of 35% (range, 5% to 91%) of engrafted cells present in the murine BM were leukemic. BM engraftment was multilineage with myeloid, B-cell, and T-cell engraftment, whereas T cells were the predominant cell type in the spleen. BM morphology showed evidence of eosinophilia and increased megakaryocytes. We also assessed the ability of selected CD34+ CML blood cells to engraft NOD/SCID mice and showed engraftment with cell doses of 7 to 10 x 10(6) cells. CD34- cells failed to engraft at cell doses of 1.2 to 5 x 10(7). CD34+ cells produced myeloid and B-cell engraftment with high levels of CD34+ cells detected. Thus, normal and leukemic stem cells are present in CD34+ blood cells from CML patients at diagnosis and lead to development of the typical features of CML in murine BM. This model is suitable to evaluate therapy in CML.


Distinction of the object recognition and object identification in the brain-computer interfaces applications.
Object recognition is a complex cognitive process in which information is integrated and processed by various brain regions. Previous studies have shown that both the visual and temporal cortices are active during object recognition and identification. However, although object recognition and object identification are similar, these processes are considered distinct functions in the brain. Despite this, the differentiation between object recognition and identification has yet to be clearly defined for use in brain-computer interface (BCI) applications. This research aims to utilize neural features related to object recognition and identification and classify these features to differentiate between the two processes. The results demonstrate that several classifiers achieved high levels of accuracy, with the XGBoost classifier using a Linear Booster achieving the highest accuracy at 96% and a F1 score of 0.97. This ability to distinguish between object recognition and identification can be a beneficial aspect of a BCI object recognition system as it could help determine the intended target object for a user.


Introducing teamwork in physician groups: a case study.
Authors Thomas N. Tavantzis, Ed.D., Carla J. Krasnik, M.B.A., M.S.N., and A. Douglas Bender, Ph.D., try team building as a basis for increasing quality and performance in a medical practices. Through the use of the Myers-Briggs Type Inventory, physicians were better able to understand their interrelationships and build more of a team feeling in the practice.


Acute heat treatment improves insulin-stimulated glucose uptake in aged skeletal muscle.
Aging is associated with insulin resistance and decreased insulin-stimulated glucose uptake into skeletal muscle. Although the mechanisms underlying age-related insulin resistance are not clearly defined, impaired defense against inflammation and tissue oxidative stress are likely causes. Heat shock proteins (HSPs) have been shown to protect tissue from oxidative stress and inhibit the activation of stress kinases such as JNK, known to interfere with the insulin signaling pathway. While the induction of HSPs via chronic heat treatment has been shown to protect skeletal muscle from obesity-related insulin resistance, the ability of heat treatment to improve insulin action in aged skeletal muscle is not known. In the present study, one bout of in vivo heat treatment applied to 24-mo-old Fischer 344 rats improved insulin-stimulated glucose uptake after 24 h in slow-twitch soleus muscles. In vitro heat treatment applied to young (3-mo-old) and aged (24-mo-old) soleus muscles increased expression of HSP72 and inhibited anisomycin-induced activation of JNK. In contrast, heat treatment had no effect on p38 MAPK, a MAPK strongly activated with anisomycin. Prior inhibition of HSP72 transcription with the pharmacological inhibitor KNK437 eliminated the ability of heat treatment to blunt JNK activation. This suggests that the ability of heat treatment to inhibit JNK activation in skeletal muscle is dependent on increased HSP72 expression. In conclusion, an acute bout of heat treatment can increase insulin-stimulated glucose uptake in aged skeletal muscle, with the underlying mechanism likely to be HSP72-mediated JNK inhibition.


Human immunodeficiency virus type 1 neutralization by plasma from B or F genotype infected individuals.
Anti-human immunodeficiency virus type 1 (HIV-1) "binding antibodies" (antibodies capable of binding to synthetic peptides or proteins) occur throughout HIV-1 infection, are high-titered and highly cross-reactive, as confirmed in this study by analyzing plasma from B and F genotype HIV-1 infected individuals. Plasma from individuals infected with clade F HIV-1 displayed the most frequent cross-reactivity, in high titers, while Bbr plasma showed much higher specificity. Similarly, neutralization of a reference HIV-1 isolate (HIV-1 MN) was more frequently observed by plasma from F than B genotype infected individuals. No significant difference was seen in neutralization susceptibility of primary B, Bbr or F clade HIV-1 by plasma from individuals infected with the classical B (GPGR) or F HIV-1, but Bbr (GWGR) plasma were less likely to neutralize the F genotype primary HIV-1 isolates. The data indicate that both B and F genotype derived vaccines would be equally effective against B and F HIV-1 infection, with a slightly more probable effectiveness for F than B genotype. Although the Bbr variant appears to induce a much more specific humoral immune response, the susceptibility in neutralizing the Brazilian HIV-1 B genotype Bbr variant is similar to that observed with the classical B genotype HIV-1.


Investigation of the oviductal glycoprotein 1 (OVGP1) gene associated with embryo survival and development in the rabbit.
An association study was performed in rabbits between early embryo survival and development, and the nonconservative SNP 12944C>G located in exon 11 and the triallellic microsatellite [(GT)(15)T(G)(5), (GT)(14)T(G)(5), and (GT)(11)T(G)(7))] located in the promoter region of the oviductal glycoprotein 1 (OVGP1) gene. We analyzed an F(2) cross of 2 lines of rabbits divergently selected for uterine capacity. A total of 172 and 159 females were slaughtered at 48 and 72 h of gestation, respectively, to determine whether OVGP1 influences ovulation rate, fertilization rate, early embryo survival, and embryonic stage of development. The results of the SNP indicated that all genotypes showed similar early embryo survival and a similar embryonic stage of development at 48 h of gestation. However, at 72 h of gestation, the GG genotype showed greater early embryo survival than the CC genotype (0.56 embryos) and their embryos presented less embryonic development. Analysis of the microsatellite was performed to ascertain the presence or absence of the allele (GT)(14)T(G)(5). At both stages of gestation, the (GT)(14)T(G)(5)/(GT)(14)T(G)(5) genotype showed greater early embryo survival (0.94 and 1.54 embryos at 48 and 72 h of gestation, respectively) and less embryonic development than the homozygous genotypes without the allele (GT)(14)T(G)(5).


An Investigation of the Impact of Expanding High-Deductible Health Plans on Patient Decision for Cochlear Implant Surgery and Postoperative Outcomes.
After the expansion of high deductibles, patients will delay cochlear implant (CI) surgery to the end of the year, and the risk of postoperative known risks will increase. The Affordable Care Act was associated with increased enrollment in high-deductible health plans (HDHPs), which resulted in rising health insurance deductibles. Health insurance plans can cover a patient's cost of healthcare once the deductible is met. Patients have been shown to be economic rational decision makers and make decisions based on cost rather than health. They wait for their deductible to be met, typically at the end of the year, then proceed to have costly care. The goal of this study was to evaluate the impact of rising health insurance deductibles on the rate and postoperative outcomes of cochlear implantation and to assess changes by the Tax Cuts and Jobs Act. TriNetX was used to accumulate summary data on patients who obtained a CI between 2005 and 2022 at the beginning (quarter 1) and the end of the year (quarter 4) from the electronic medical records of 75 healthcare organizations. The trends in average rate of cochlear implantation and resultant postoperative known risks or complications were statistically evaluated. After expansion of HDHPs, the rate of cochlear implantation between quarter 4 (19 cases per year) and quarter 1 (17 cases/year) was similar (p = 0.18). For all patient groups, the case volume significantly increased. Between quarter 4 and quarter 1, postoperative tinnitus was more common in the beginning of the year (risk ratio, 0.68; 95% confidence interval, 0.46-0.99). The number of patients receiving CIs significantly increased despite the expansion of HDHPs. Tinnitus was a rare postoperative known risk in the beginning of the year. Patients are less likely concerned about cost of CI surgery because of the impact of hearing loss on quality of life.


Ectomycorrhizal fungi enhance pine growth by stimulating iron-dependent mechanisms with trade-offs in symbiotic performance.
Iron (Fe) is crucial for metabolic functions of living organisms. Plants access occluded Fe through interactions with rhizosphere microorganisms and symbionts. Yet, the interplay between Fe addition and plant-mycorrhizal interactions, especially the molecular mechanisms underlying mycorrhiza-assisted Fe processing in plants, remains largely unexplored. We conducted mesocosms in Pinus plants inoculated with different ectomycorrhizal fungi (EMF) Suillus species under conditions with and without Fe coatings. Meta-transcriptomic, biogeochemical, and X-ray fluorescence imaging analyses were applied to investigate early-stage mycorrhizal roots. While Fe addition promoted Pinus growth, it concurrently reduced mycorrhiza formation rate, symbiosis-related metabolites in plant roots, and aboveground plant carbon and macronutrient content. This suggested potential trade-offs between Fe-enhanced plant growth and symbiotic performance. However, the extent of this trade-off may depend on interactions between host plants and EMF species. Interestingly, dual EMF species were more effective at facilitating plant Fe uptake by inducing diverse Fe-related functions than single-EMF species. This subsequently triggered various Fe-dependent physiological and biochemical processes in Pinus roots, significantly contributing to Pinus growth. However, this resulted in a greater carbon allocation to roots, relatively reducing the aboveground plant carbon content. Our study offers critical insights into how EMF communities rebalance benefits of Fe-induced effects on symbiotic partners.


Conditioned medium obtained from human amniotic membrane-derived mesenchymal stem cell attenuates heart failure injury in rats.
Heart failure (HF) is one of the leading causes of death worldwide. Due to beneficial effects of stem cells, paracrine secretion of them has recently been used by researchers. The purpose of this study was to investigate the effects of intravenous injection (IV) of conditioned medium (CM) of human amniotic membrane-derived mesenchymal stem cell (MSC-CM) on HF. Male Wistar rats (n=35, 180 g) were randomly divided into five groups: sham, HF, HF+MSC-CM, HF+culture medium and HF+phosphate-buffered saline (PBS). To induce HF, isoproterenol (170 mg/kg/d) was injected subcutaneously for 4 consecutive days. After 28 days, induction of HF was evaluated by echocardiography. A day after echocardiography, 50 μg culture medium/5 ml PBS in HF+culture medium group, 50 μg MSC-CM/5 ml PBS in HF+MSC-CM group and 5 ml PBS in HF+PBS group were injected two times for 4 successive days. The echocardiography was performed 4 weeks after the last injection of isoproterenol. To evaluate the fibrosis, morphology, and cardiac function, Trichrome Masson's staining, Hematoxylin and Eosin staining and echocardiography were performed, respectively. CM significantly increased fractional shortening and ejection fraction, and also significantly decreased apoptotic nuclear condensation. Moreover, significant decreased level of fibrosis and increased level of angiogenesis was observed in the treatment group (P<0.05). Our results indicated that IV injection of CM has therapeutic effects on HF by reducing fibrosis and preventing the progression of failure due to its paracrine effects.


[The Effects of Therapy for Iron Deficiency in Patients With Different Etiologies of Heart Failure and Concomitant Diseases].
Iron deficiency (ID) in patients with heart failure (HF) is a factor for unfavorable course and prognosis of the disease. The significance of ID in the diagnosis and treatment of HF has previously been demonstrated by multiple studies and meta-analyses. Therapy for ID in patients with HF is one of the most relevant and discussed issues. The use of intravenous iron medicinal products for the treatment of ID is currently being actively studied in patients of various categories; attempts are being made to specify the indications for use to produce the greatest effect on the prognosis and quality of life of HF patients.


[Cost-benefit analysis of practical occupational medicine service].
Cost problems in business, industry and government service force everyone to probe into the economy of traditional patterns of work and procedures. Occupational medicine is no exception. However, there has been a lack of criteria for assessing the economic aspects of occupational medicine. We are therefore suggesting an approach. Caring for the "human capital" factor is a cornerstone of free socioeconomy. Workers should not only be suitably qualified for their job but there must be the smallest possible minimum of absenteeism. Occupational medicine can do something to positively influence the following factors: by preventing incapacity to work by preventing job accidents and professional diseases by reducing the time required to cover distances between or within workflow phases or stages by reducing waste of time by waiting. Model calculations, based on highly plausible basic postulates, show that fully integrated occupational medical services are throughout economic and cost-saving. Using a concrete example, we arrived at a cost/benefit ratio of 1:2 while confining ourselves to benefits attainable within a relatively short time. We ignored other, future benefits requiring certain preventive measures, as well as other parameters that are difficult to assess, such as corporate identity. At present occupational medicine faces a certain amount of identity crisis which should not be counteracted by pointing to legislation that justifies its existence, but rather by proving that it is indeed highly economical because it saves time and money.


Nanoparticle-based diagnostic and therapeutic systems for brain tumors.
Brain tumors, especially the most prevalent and aggressive glioblastoma, remain among the deadliest of all types of cancer due to inefficient theranostic options. They have a limited therapeutic window because of physiological barriers such as the blood-brain barrier (BBB), blood cerebrospinal fluid (CSF) barrier and interstitial fluid (ISF) that restrict the penetration of imaging probes and therapeutic drugs. In order to achieve more accurate brain tumor diagnosis and better therapeutic effects, many strategies have been explored; among them multifunctional nanoparticles offer a novel and potential opportunity depending on their size effects, and their optical, magnetic, photodynamic and other properties. After modification, nanoparticles can cross the BBB and specifically accumulate in the tumor site, thereby achieving accurate tumor imaging and drug release. This review is focused on various types of nanoparticles that are being used for improving nano-carriers of diagnostic and therapeutic agents into brain tumors and also provides a concise summary of various multifunctional theranostic strategies, particularly in clinical applications. In this manner, we provide evidence for the key role of nanoparticle based diagnosis and therapy systems in brain tumors.


Characterization of the promiscuous N-acyl CoA transferase, LgoC, in legonoxamine biosynthesis.
More than 500 siderophores are known to date, but only three were identified to be aryl-containing hydroxamate siderophores, legonoxamines A and B from Streptomyces sp. MA37, and aryl ferrioxamine 2 from Micrococcus luteus KLE1011. Siderophores are produced by microorganisms to scavenge iron from the environment, thereby making this essential metal nutrient available to the microbe. We demonstrate here that LgoC from MA37 is responsible for the key aryl-hydroxamate forming step in legonoxamine biosynthesis. Biochemical characterization established that LgoC displays considerable promiscuity for the acylation between N-hydroxy-cadaverine and SNAC (N-acetylcysteamines) thioester derivatives.


In vivo interaction of von Willebrand factor with platelets following cryoprecipitate transfusion in platelet-type von Willebrand's disease.
Previous studies performed in vitro have indicated that platelets from patients with platelet-type von Willebrand's disease (vWD) have receptors for von Willebrand factor (vWF) already exposed on their surfaces and that the addition of purified vWF or cryoprecipitate to patient platelet-rich plasma under stirring conditions is capable of inducing platelet aggregation and secretion. The present work reports the results of the transfusion of cryoprecipitate in a patient with platelet-type vWD. It is shown that, while factor VIII-related antigen and ristocetin cofactor activities maintain elevated levels for up to 12 hr following transfusion, the highest molecular weight vWF multimers decline rapidly. The platelet count also declines, followed in turn by a rise in the plasma level of platelet factor 4. Shortening of the bleeding time occurs only very transiently. The results of this study provide direct evidence that, in patients with platelet-type vWD, an abnormal interaction of their platelets with plasma vWF occurs in vivo, resulting in the absence of high molecular weight vWF multimers, low platelet counts, and impaired hemostasis that are characteristic of this disease.


Cultivable bacterial microbiota of northern bobwhite (Colinus virginianus): a new reservoir of antimicrobial resistance?
The northern bobwhite (Colinus virginianus) is an ecologically and economically important avian species. At the present time, little is known about the microbial communities associated with these birds. As the first step to create a quail microbiology knowledge base, the current study conducted an inventory of cultivable quail tracheal, crop, cecal, and cloacal microbiota and associated antimicrobial resistance using a combined bacteriology and DNA sequencing approach. A total of 414 morphologically unique bacterial colonies were selected from nonselective aerobic and anaerobic cultures, as well as selective and enrichment cultures. Analysis of the first 500-bp 16S rRNA gene sequences in conjunction with biochemical identifications revealed 190 non-redundant species-level taxonomic units, representing 160 known bacterial species and 30 novel species. The bacterial species were classified into 4 phyla, 14 orders, 37 families, and 59 or more genera. Firmicutes was the most commonly encountered phylum (57%) followed by Actinobacteria (24%), Proteobacteria (17%) and Bacteroidetes (0.02%). Extensive diversity in the species composition of quail microbiota was observed among individual birds and anatomical locations. Quail microbiota harbored several opportunistic pathogens, such as E. coli and Ps. aeruginosa, as well as human commensal organisms, including Neisseria species. Phenotypic characterization of selected bacterial species demonstrated a high prevalence of resistance to the following classes of antimicrobials: phenicol, macrolide, lincosamide, quinolone, and sulphate. Data from the current investigation warrant further investigation on the source, transmission, pathology, and control of antimicrobial resistance in wild quail populations.


Impact of CYP2C9-Interacting Drugs on Warfarin Pharmacogenomics.
Precise dosing of warfarin is important to achieve therapeutic benefit without adverse effects. Pharmacogenomics explains some interindividual variability in warfarin response, but less attention has been paid to drug-drug interactions in the context of genetic factors. We investigated retrospectively the combined effects of cytochrome P450 (CYP)2C9 and vitamin K epoxide reductase complex (VKORC)1 genotypes and concurrent exposure to CYP2C9-interacting drugs on long-term measures of warfarin anticoagulation. Study participants predicted to be sensitive responders to warfarin based on CYP2C9 and VKORC1 genotypes, had significantly greater international normalized ratio (INR) variability over time. Participants who were concurrently taking CYP2C9-interacting drugs were found to have greater INR variability and lesser time in therapeutic range. The associations of INR variability with genotype were driven by the subgroup not exposed to interacting drugs, whereas the effect of interacting drug exposure was driven by the subgroup categorized as normal responders. Our findings emphasize the importance of considering drug interactions in pharmacogenomic studies.


Lower plasma vitamin E levels are associated with the frailty syndrome: the InCHIANTI study.
The primary biologic mechanism that causes frailty in older persons has never been adequately explained. According to recent views, oxidative stress may be the driving force of this condition. We tested the hypothesis that, independent of confounders, low plasma levels of vitamin E (alpha-tocopherol), the main fat-soluble human antioxidant, are associated with the frailty syndrome in older persons free from dementia and disability. The study sample included 827 older (> or =65 years) persons (women, 54%) who participated in a population-based epidemiological study. Frail participants were identified based on the presence of at least three of five of the following features: self-reported weight loss, low energy, slow gait speed, low grip strength, and low physical activity. Participants with none of these features were considered nonfrail, while participants with one or two were considered intermediate frail. Plasma vitamin E levels were determined using reverse-phase high-performance liquid chromatography. Measured confounders included lower extremity muscle strength, cognitive function, diseases, and factors related to vitamin E metabolism. Age- and gender-adjusted levels of vitamin E decreased gradually from the nonfrail to the frail group (p for trend =.015). In the logistic model adjusted for multiple potential confounders, participants in the highest vitamin E tertile were less likely to be frail than were participants in the lowest vitamin E tertile (odds ratio, 0.30; 95% confidence interval, 0.10-0.91). Our findings show an association between low circulating levels of one of the most important components of the human antioxidant system and the presence of frailty.


Reductive metabolism of aromatic nitro compounds including carcinogens by rabbit liver preparations.
Reductive metabolism of aromatic nitro compounds was examined with rabbit liver preparations. Under anaerobic conditions, carcinogenic 2-nitrofluorene, 4-nitrobiphenyl, and 1-nitro-naphthalene were reduced to the corresponding hydroxylamines and amines, whereas the carcinogenic 1-nitropyrene was reduced only to the corresponding amine by liver cytosol in the presence of 2-hydroxypyrimidine, an electron donor of aldehyde oxidase. These metabolites were identified unequivocally by comparing their mass spectra and thin-layer chromatographic behaviors with those of the authentic samples. Both liver microsomes and cytosol catalyzed the reduction of these aromatic nitro compounds in varying degrees. The microsomes required reduced pyridine nucleotides for occurrence of the nitroreductase activities. In this case, reduced nicotinamide adenine dinucleotide phosphate was more effective than reduced nicotinamide adenine dinucleotide as an electron donor. The cytosol by itself exhibited some nitroreductase activities, which were markedly enhanced by addition of an electron donor of aldehyde oxidase, i.e., N1-methylnicotinamide or 2-hydroxypyrimidine. The full activities of the cytosol with the electron donor were much higher than those of the microsomes with the reduced pyridine nucleotide. Purified liver aldehyde oxidase, like the cytosol, exhibited significant nitroreductase activities in the presence of its electron donor. These results indicated that cytosolic aldehyde oxidase functions as a major enzyme responsible for the reduction of aromatic nitro compounds including carcinogens in rabbit liver.


Five-year experience of critical incidents associated with patient-controlled analgesia in an Irish University Hospital.
Patient-controlled analgesia (PCA) is a common and effective means of managing post-operative pain. We sought to identify factors that may lead to critical incidents (CIs) in patient safety when using PCA in our institution. An observational study of prospectively collected data of patients who received PCA from 2002 to 2006 was performed. All CIs were documented and analysed by staff members of the acute pain service (APS). Cause analysis of CIs was undertaken to determine if measures can be instituted to prevent recurrence of similar events. Over eight thousand patients (8,240) received PCA. Twenty-seven CIs were identified. Eighteen were due to programming errors. Other CIs included co-administration of opioids and oversedation. In our institution, the largest contributory factor to CIs with PCAs was programming error. Strategies to minimize this problem include better education and surveillance.


The hierarchical structure of images.
Using a Gaussian scale space, one can use the extra dimension, viz. scale, for investigation of "built-in" properties of the image in scale space. We show that one of such induced properties is the nesting of special iso-intensity manifolds, which yield an implicitly present hierarchy of the critical points and regions of their influence, in the original image. Its very nature allows one not only to segment the original image automatically, but also to apply "logical filters" to it, obtaining simplified images. We give an algorithm deriving this hierarchy and show its effectiveness on two different kinds of images, both with respect to segmentation and simplification.


Left ventricular function in ischaemic heart disease. A review.
The clinical significance of the abnormalities seen at left ventriculography in ischaemic heart disease is discussed. Aneurysms may be recognized when left ventriculography is combined with coronary arteriography to show the characteristic obliteration of the supplying artery. Localized areas of abnormal contraction seen at rest are almost certainly indicative of infarcts. Similar areas provoked by exercise or atrial pacing represent the site of acute ischaemia. The ischaemic ventricle may be recognized by abnormal response to exercise, even in the absence of angina. The abnormal response may be reversed by successful revascularization surgery.