[Isolation and characterization of lactate dehydrogenase from white fin muscles of the skate Raja clavata].
Lactate dehydrogenase (LDH) from white driving muscle of skate Raja clavata was purified by the differential precipitation of ammonium sulphate between 52 and 55% saturation. Only one protein band with the LDH activity was obtained by nondenaturing electrophoresis. The same result was obtained by the SDS-electrophoresis. The relative molecular weight calculated by this method in the presence of DS-Na was 34 kDa; Km was 29 +/- 7 and 71 +/- 16 microM for NAD.H and pyruvate, respectively. The reaction was maximally activated by 0.8-6.0 mM pyruvate and inhibited in the regions above this level. Dilution of LDH below concentration of 1 microgram/ml reduced the enzyme activity. The pH-optimum for the LDH activity ranged 7.0-8.0.


From cultural traditions to cumulative culture: parameterizing the differences between human and nonhuman culture.
Diverse species exhibit cultural traditions, i.e. population-specific profiles of socially learned traits, from songbird dialects to primate tool-use behaviours. However, only humans appear to possess cumulative culture, in which cultural traits increase in complexity over successive generations. Theoretically, it is currently unclear what factors give rise to these phenomena, and consequently why cultural traditions are found in several species but cumulative culture in only one. Here, we address this by constructing and analysing cultural evolutionary models of both phenomena that replicate empirically attestable levels of cultural variation and complexity in chimpanzees and humans. In our model of cultural traditions (Model 1), we find that realistic cultural variation between populations can be maintained even when individuals in different populations invent the same traits and migration between populations is frequent, and under a range of levels of social learning accuracy. This lends support to claims that putative cultural traditions are indeed cultural (rather than genetic) in origin, and suggests that cultural traditions should be widespread in species capable of social learning. Our model of cumulative culture (Model 2) indicates that both the accuracy of social learning and the number of cultural demonstrators interact to determine the complexity of a trait that can be maintained in a population. Combining these models (Model 3) creates two qualitatively distinct regimes in which there are either a few, simple traits, or many, complex traits. We suggest that these regimes correspond to nonhuman and human cultures, respectively. The rarity of cumulative culture in nature may result from this interaction between social learning accuracy and number of demonstrators.


Self-efficacy, recovery and psychological wellbeing one to five years after heart transplantation: a Swedish cross-sectional study.
Self-efficacy refers to a person´s confidence in carrying out treatment-related activities and constitutes the foundation of self-management as well as long-term follow-up after heart transplantation. Exploring the heart recipients´ experiences by means of self-report instruments provides healthcare professionals with valuable information on how to supply self-management support after heart transplantation. The aim was to explore self-efficacy in relation to the self-reported level of recovery and psychological wellbeing, among adult heart recipients, one to 5 years after transplantation. This cross-sectional study includes 79 heart recipients, due for follow-up one to 5 years after transplantation. Three different self-assessment instruments were employed: the self-efficacy for managing chronic disease 6-item scale; the postoperative recovery profile; and the psychological general wellbeing instrument. The reported level of self-efficacy was high (median 8.3, maximum score 10). Significantly higher self-efficacy was seen among those who had returned to work (P = 0.003) and those without pre-transplant mechanical circulatory support (P = 0.033). In total, 65.5% (n = 52) reported being reasonably recovered, while 18.8% (n = 12) were not recovered. The median total psychological general wellbeing score was 108 (P25 = 24, P75 = 117), suggesting overall good psychological wellbeing in the whole group of heart recipients. The heart transplant recipients in our study had an overall high level of self-efficacy. Low self-efficacy was found among those with a low self-reported level of recovery, pre-transplant treatment with mechanical circulatory support or who had not returned to work. This is important information for transplant professionals when helping heart recipients to balance their expectations about recovery.


The brown bear as a translational model for sedentary lifestyle-related diseases.
Sedentary lifestyle accelerates biological ageing, is a major risk factor for developing metabolic syndrome and is associated with cardiovascular disease, diabetes mellitus, kidney failure, sarcopenia and osteoporosis. In contrast to the linear path to worsening health in humans with metabolic syndrome, brown bears have developed a circular metabolic plasticity enabling these animals to tolerate obesity and a 'sedentary lifestyle' during hibernation and exit the den metabolically healthy in spring. Bears are close to humans physiology wise, much closer than rodents, the preferred experimental animals in medical research, and may better serve as translational model to develop treatments for lifestyle-related diseases. In this review, aspects of brown bear hibernation survival strategies are outlined and conceivable experimental strategies to learn from bears are described.


Histoplasmosis presenting as isolated cervical lymphadenopathy: A rare presentation.
Histoplasmosis is an opportunistic fungal infection caused by inhaling the spores of a fungus called Histoplasma capsulatum. Disseminated histoplasmosis is the most common form associated with acquired immune deficiency syndrome (AIDS). Here, we report a case of histoplasmosis presenting as isolated cervical lymphadenopathy in a human immunodeficiency virus (HIV)-infected patient diagnosed by a less invasive method (fine-needle aspiration cytology) and confirmed by fungal culture of fine-needle aspiration material. Due to varied and nonspecific clinical manifestations of histoplasmosis, most of the infections are misdiagnosed or underreported. It has to be considered in differential diagnosis of cervical lymphadenopathy, particularly in immunocompromised patients so that patients can be treated medically at an early stage before dissemination occurs and unnecessary surgery can be avoided. Here, we present this case because of its rare presentation as isolated cervical lymphadenopathy and classical cytological picture.


Magnetite as a precursor for green rust through the hydrogenotrophic activity of the iron-reducing bacteria Shewanella putrefaciens.
Magnetite (Fe(II) Fe(III) 2 O4 ) is often considered as a stable end product of the bioreduction of Fe(III) minerals (e.g., ferrihydrite, lepidocrocite, hematite) or of the biological oxidation of Fe(II) compounds (e.g., siderite), with green rust (GR) as a mixed Fe(II) -Fe(III) hydroxide intermediate. Until now, the biotic transformation of magnetite to GR has not been evidenced. In this study, we investigated the capability of an iron-reducing bacterium, Shewanella putrefaciens, to reduce magnetite at circumneutral pH in the presence of dihydrogen as sole inorganic electron donor. During incubation, GR and/or siderite (Fe(II) CO3 ) formation occurred as secondary iron minerals, resulting from the precipitation of Fe(II) species produced via the bacterial reduction of Fe(III) species present in magnetite. Taking into account the exact nature of the secondary iron minerals and the electron donor source is necessary to understand the exergonic character of the biotic transformation of magnetite to GR, which had been considered to date as thermodynamically unfavorable at circumneutral pH. This finding reinforces the hypothesis that GR would be the cornerstone of the microbial transformations of iron-bearing minerals in the anoxic biogeochemical cycle of iron and opens up new possibilities for the interpretation of the evolution of Earth's history and for the understanding of biocorrosion processes in the field of applied science.


Reconsidering scarce drug rationing: implications for clinical research.
Hospital systems commonly face the challenge of determining just ways to allocate scarce drugs during national shortages. There is no standardised approach of how this should be instituted, but principles of distributive justice are commonly used so that patients who are most likely to benefit from the drug receive it. As a result, clinical indications, in which the evidence for the drug is assumed to be established, are often prioritised over research use. In this manuscript, we present a case of a phase II investigational trial of intravenous thiamine for delirium prevention in patients undergoing haematopoietic stem cell transplantation to emphasise several shortcomings in the overarching prioritisation of clinical over research uses of scarce drugs. Specifically, we present the following considerations: (1) clinical use may not have stronger evidence than research use; (2) a strong scientific rationale for research use may outweigh the claim for clinical indications in which there is weak evidence; (3) treatment within the context of a clinical trial may be the standard of care; and (4) research use may not only benefit patients receiving the treatment but also offers the prospect of improving future clinical care. In summary, we argue against allocation schemes that prohibit all research uses of scarce drugs and instead recommend that allocation schemes include a balanced approach that weighs risks and benefits of access to scarce drugs irrespective of the research versus clinical use designation.


Efficacy of Acupuncture in Children with Nocturnal Enuresis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Background. Nocturnal enuresis (NE) is recognized as a widespread health problem in young children and adolescents. Clinical researches about acupuncture therapy for nocturnal enuresis are increasing, while systematic reviews assessing the efficacy of acupuncture therapy are still lacking. Objective. This study aims to assess the effectiveness of acupuncture therapy for nocturnal enuresis. Materials and Methods. A comprehensive literature search of 8 databases was performed up to June 2014; randomized controlled trials which compared acupuncture therapy and placebo treatment or pharmacological therapy were identified. A meta-analysis was conducted. Results. This review included 21 RCTs and a total of 1590 subjects. The overall methodological qualities were low. The results of meta-analysis showed that acupuncture therapy was more effective for clinical efficacy when compared with placebo or pharmacological treatment. Adverse events associated with acupuncture therapy were not documented. Conclusion. Based on the findings of this study, we cautiously suggest that acupuncture therapy could improve the clinical efficacy. However, the beneficial effect of acupuncture might be overstated due to low methodological qualities. Rigorous high quality RCTs are urgently needed.


Extreme divergence in floral scent among woodland star species (Lithophragma spp.) pollinated by floral parasites.
A current challenge in coevolutionary biology is to understand how suites of traits vary as coevolving lineages diverge. Floral scent is often a complex, variable trait that attracts a suite of generalized pollinators, but may be highly specific in plants specialized on attracting coevolved pollinating floral parasites. In this study, floral scent variation was investigated in four species of woodland stars (Lithophragma spp.) that share the same major pollinator (the moth Greya politella, a floral parasite). Three specific hypotheses were tested: (1) sharing the same specific major pollinator favours conservation of floral scent among close relatives; (2) selection favours 'private channels' of rare compounds particularly aimed at the specialist pollinator; or (3) selection from rare, less-specialized co-pollinators mitigates the conservation of floral scent and occurrence of private channels. Dynamic headspace sampling and solid-phase microextraction were applied to greenhouse-grown plants from a common garden as well as to field samples from natural populations in a series of experiments aiming to disentangle the genetic and environmental basis of floral scent variation. Striking floral scent divergence was discovered among species. Only one of 69 compounds was shared among all four species. Scent variation was largely genetically based, because it was consistent across field and greenhouse treatments, and was not affected by visits from the pollinating floral parasite. The strong divergence in floral scents among Lithophragma species contrasts with the pattern of conserved floral scent composition found in other plant genera involved in mutualisms with pollinating floral parasites. Unlike some of these other obligate pollination mutualisms, Lithophragma plants in some populations are occasionally visited by generalist pollinators from other insect taxa. This additional complexity may contribute to the diversification in floral scent found among the Lithophragma species pollinated by Greya moths.


Pythium abappressorium--a new species from eastern Washington.
A new species of Pythium isolated from wheat and apple roots in eastern Washington is described. Pythium abappressorium sp. nov. is characterized by abundant appressoria. Plerotic oospores and sporangia are formed from the appressoria and remnants of the appressoria remain attached to the base of sporangia at maturity. Smaller appressorial swellings, reminiscent of hyphal swellings, are also formed within the appressoria. Pythium abappressorium is pathogenic to wheat, causing damping-off and stunting, but is not pathogenic to apples. The fungus can grow in the temperature range 5 to 30 C, with an optimum of 20 C. The sequence of the ITS1 region of the rDNA did not match the sequences from a worldwide collection of over 1200 isolates, including types and neotypes, suggesting that this species has not been previously described.


Effects of a combined aerobic and resistance exercise program on C1q/TNF-related protein-3 (CTRP-3) and CTRP-5 levels.
To examine the effect of a combined exercise program on C1q/tumor necrosis factor-related protein (CTRP) 3 and CTRP-5 levels and novel adiponectin paralogs suggested to be links between metabolism and inflammation and to evaluate sex differences and association with cardiometabolic risk factors in humans with use of a newly developed ELISA. This cross-sectional study explored the implications of CTRP-3 and CTRP-5 on cardiometabolic parameters in 453 nondiabetic Korean adults. In addition, we evaluated the impact of a 3-month combined exercise program on CTRP-3 and CTRP-5 levels in 76 obese women. The exercise program consisted of 45 min of aerobic exercise at an intensity of 60-75% of the age-predicted maximum heart rate (300 kcal/session) and 20 min of resistance training (100 kcal/session) five times per week. Both CTRP-3 and CTRP-5 concentrations were significantly higher in women (P<0.001) than in men (P=0.030). In a multiple stepwise regression analysis, CTRP-3 levels were independently associated with age, sex, and triglyceride, LDL cholesterol, adiponectin, and retinol-binding protein 4 (RBP4) levels (R2=0.182). After 3 months of a combined exercise program, cardiometabolic risk factors, including components of metabolic syndrome, insulin resistance, and RBP4 levels, decreased significantly. In particular, CTRP-3 levels decreased significantly (median [interquartile range] 444.3 [373.8-535.0] to 374.4 [297.2-435.9], P<0.001), whereas CTRP-5 levels were slightly increased (34.1 [28.6-44.3] to 38.4 [29.8-55.1], P=0.048). A 3-month combined exercise program significantly decreased CTRP-3 levels and modestly increased CTRP-5 levels in obese Korean women.


Hydrogen peroxide yields during the incompatible interaction of tobacco suspension cells inoculated with Phytophthora nicotianae.
Rates of H(2)O(2) production by tobacco suspension cells inoculated with zoospores from compatible or incompatible races of the pathogen Phytophthora nicotianae were followed by direct measurement of oxygen evolution from culture supernatants following catalase addition. Rates of HO(2)(*)/O(2)(-) production were compared by following the formation of the formazan of sodium, 3'-[1-[phenylamino-carbonyl]-3,4-tetrazolium]-bis(4-methoxy-6-nitro) benzene-sulfonic acid hydrate. In the incompatible interaction only, both reactive oxygen species (ROS) were produced by the cultured host cells in a minor burst between 0 and 2 h and then in a major burst between 8 and 12 h after inoculation. Absolute levels of H(2)O(2) could not be accurately measured due to its metabolism by host cells, but results are consistent with the majority of H(2)O(2) being formed via dismutation of HO(2)(*)/O(2)(-). The effects of inhibitors of endogenous Cu/Zn superoxide dismutase (diethyldithiocarbamate) and catalase (3-amino-1,2,4-triazole and salicylic acid) were also examined. Yields of ROS in the presence of the inhibitors diphenylene iodonium, allopurinol, and salicylhydroxamic acid suggest that ROS were generated in incompatible host responses by more than one mechanism.


[Occupational medicine: health protection of liquidation specialists].
Taking long-term clinical and epidemiologic observation of rescue team (helicopter pilots) as an example, the authors defined principal concepts concerning prophylaxis, social security and rehabilitation of Chernobyl plant accident liquidators. Methodology and methods of the liquidators' health care are discussed.


Killer whale (Orcinus orca) interactions with blue-eye trevalla (Hyperoglyphe antarctica) longline fisheries.
Over the past five decades, marine mammal interactions with fisheries have become a major human-wildlife conflict globally. The emergence of longline fishing is concomitant with the development of depredation-type interactions i.e., marine mammals feeding on fish caught on hooks. The killer whale (Orcinus orca) is one of the species most involved in depredation on longline fisheries. The issue was first reported in high latitudes but, with increasing expansion of this fishing method, other fisheries have begun to experience interactions. The present study investigated killer whale interactions with two geographically isolated blue-eye trevalla (Hyperoglyphe antarctica) fisheries operating in temperate waters off Amsterdam/St. Paul Islands (Indian Ocean) and south-eastern Australia. These two fisheries differ in the fishing technique used (vertical vs. demersal longlines), effort, catch, fleet size and fishing area size. Using 7-year (2010-16) long fishing and observation datasets, this study estimated the levels of killer whale interactions and examined the influence of spatio-temporal and operational variables on the probability of vessels to experience interactions. Killer whales interactions occurred during 58.4% and 21.2% of all fishing days, and over 94% and 47.4% of the fishing area for both fisheries, respectively. In south-eastern Australia, the probability of occurrence of killer whale interactions during fishing days varied seasonally with a decrease in spring, increased with the daily fishing effort and decreased with the distance travelled by the vessel between fishing days. In Amsterdam/St. Paul, this probability was only influenced by latitude, with an increase in the southern part of the area. Together, these findings document two previously unreported cases of high killer whale depredation, and provide insights on ways to avoid the issue. The study also emphasizes the need to further examine the local characteristics of fisheries and the ecology of local depredating killer whale populations in as important drivers of depredation.


Cardiac effects of beta-adrenoceptor antagonists with intrinsic sympathomimetic activity in humans: beta1- and/or beta2-adrenoceptor mediated?
The aim of this study was to find out whether cardiac responses to the beta-adrenoceptor antagonists with intrinsic sympathomimetic activity (ISA) xamoterol and celiprolol are mediated by cardiac beta1- or beta2-adrenoceptors or both. For this purpose we assessed, in six healthy male volunteers, the effects of xamoterol (100 and 200 mg, p.o.) and celiprolol (200, 600, and 1,200 mg, p.o.) on blood pressure, heart rate, and heart rate-corrected duration of the electromechanical systole (QS2c, as a measure of inotropism). Xamoterol, in both doses, increased systolic blood pressure and heart rate, transiently decreased diastolic blood pressure, and shortened QS2c; all these effects were attenuated after pretreatment of the volunteers with the beta1-adrenoceptor antagonist bisoprolol. Celiprolol, in all three doses, increased heart rate, decreased diastolic blood pressure, and shortened QS2c but only marginally increased systolic blood pressure. Bisoprolol did not attenuate these celiprolol effects but rather enhanced celiprolol effects on systolic blood pressure and heart rate. In a further set of experiments, we studied cardiovascular effects of celiprolol in six healthy volunteers whose beta2-adrenoceptors had been desensitized by a 2-week treatment with 3x5 mg/day terbutaline. Under these conditions, celiprolol failed to increase heart rate or to shorten QS2c. We conclude that, under resting conditions, in healthy volunteers, beta-adrenoceptor antagonists with ISA can exert increases in heart rate and contractility that are mediated by either cardiac beta1-adrenoceptor (xamoterol) or cardiac beta2-adrenoceptor (celiprolol) stimulation. Thus in the human heart, the ISA of beta-adrenoceptor antagonists can be a beta1- or beta2-adrenoceptor agonistic component.


Fumarate hydratase FH c.1431_1433dupAAA (p.Lys477dup) variant is not associated with cancer including renal cell carcinoma.
Fumarate hydratase (FH) mutations underpin the autosomal recessive syndrome. FH deficiency and the autosomal dominant syndrome hereditary leiomyomatosis and renal cell carcinoma (HLRCC). The FH c.1431_1433dupAAA (p.Lys477dup) genomic alteration has been conclusively shown to contribute to FH deficiency when occurring with another FH germline alteration. However, a sufficiently large dataset has been lacking to conclusively determine its clinical significance to cancer predisposition in the heterozygous state. We reviewed a series of 7,571 patients with cancer who received germline results through MSK-IMPACT testing at the Memorial Sloan Kettering Cancer Center. The FH c.1431_1433dupAAA (p.Lys477dup) variant was detected in 24 individuals, none of whom was affected with renal cancer. Eleven of the 372 patients with renal cancer were identified to carried pathogenic FH variants associated with HLRCC. None of these 372 patients with renal cancer carried the FH c.1431_1433dupAAA variant. Our data indicate the FH c.1431_1433dupAAA is not associated with cancer including renal cell carcinoma.


The coding of object thickness in plants: When roots matter.
Tendrils are clasping structures used by climbing plants to anchor and support their vines that coil around suitable hosts to achieve the greatest exposure to sunlight. Although recent evidence suggests that climbing plants are able to sense the presence of a potential stimulus in the environment and to plan the tendrils' movements depending on properties such as its thickness, the mechanisms underlying thickness sensing in climbing plants have yet to be uncovered. The current research set out to use three-dimensional kinematical analysis to investigate if and in what way the root system contributed to thickness sensing. Experiment 1 was designed to confirm that the movement of the tendrils of pea plants (Pisum sativum L.) is planned and controlled on the basis of stimulus thickness when the stimulus is inserted into the substrate. Experiment 2 was designed to investigate what happens when the stimulus is lifted to the ground so as to impede the root system from sensing it. The results confirmed that tendrils' kinematics depend on thickness when the stimulus is available to the root system but not when it is unavailable to it. These findings suggest that the root system plays a pivotal role in sensing the presence and the thickness of a stimulus and that the information perceived affects the planning and the execution of the climbing plants' reach-to-grasp movements. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Moyamoya disease presented as a case of hemiplegic migraine.
Moyamoya disease is a rare cerebral vasculopathy characterised by progressive narrowing of the major intracranial vessels and development of collateral vessels. Clinically, it presents with cerebral ischaemic or haemorrhagic events, with eventual severe morbidity and mortality. A 10-year-old girl presented with episodic vascular headache and transient left sided hemiparesis, which persisted for a few hours and was clinically labelled as sporadic hemiplegic migraine according to International Headache Society criteria. We investigated all possible causes of unusual headache. Cerebral digital subtraction angiogram was carried out and moyamoya disease was finally diagnosed.


Structural connectivity analysis reveals topological aberrations in patients with schizophrenia.
Topological analysis and the associated parameters allow elucidation of brain networks in health and illness. Evidently useful measures for defining network competency such as small-worldness can potentially improve understanding of brain connectivity and their disruptions underlying neuropsychiatric conditions such as schizophrenia. In the current study, we assessed the structural differences of brain networks in schizophrenia patients as compared with healthy controls. As proof of concept investigation, diffusion tensor imaging recordings from 2 schizophrenia patients and 2, gender and age matched, control subjects were subjected to analysis using several graph network distance metrics. Among them, those that appeared to have the ability to encode and highest sensitivity in shedding light about anatomical changes in neuron deficiency were the shortest path length and clustering coefficient parameters. Schizophrenia patients displayed comparatively lower clustering coefficient, longer path lengths and hence reduced small-worldness. These results suggest aberrant topological architecture in the structural brain networks of patients with schizophrenia, which may impact the psychopathological and cognitive manifestations of this potentially crippling illness.


On 3-D scene flow and structure recovery from multiview image sequences.
Two novel systems computing dense three-dimensional (3-D) scene flow and structure from multiview image sequences are described in this paper. We do not assume rigidity of the scene motion, thus allowing for nonrigid motion in the scene. The first system, integrated model-based system (IMS), assumes that each small local image region is undergoing 3-D affine motion. Non-linear motion model fitting based on both optical flow constraints and stereo constraints is then carried out on each local region in order to simultaneously estimate 3-D motion correspondences and structure. The second system is based on extended gradient-based system (EGS), a natural extension of two-dimensional (2-D) optical flow computation. In this method, a new hierarchical rule-based stereo matching algorithm is first developed to estimate the initial disparity map. Different available constraints under a multiview camera setup are further investigated and utilized in the proposed motion estimation. We use image segmentation information to adopt and maintain the motion and depth discontinuities. Within the framework for EGS, we present two different formulations for 3-D scene flow and structure computation. One formulation assumes that initial disparity map is accurate, while the other does not. Experimental results on both synthetic and real imagery demonstrate the effectiveness of our 3-D motion and structure recovery schemes. Empirical comparison between IMS and EGS is also reported.


Neonatal aspiration: not just meconium.
Aspiration of uncontaminated amniotic fluid as a cause of neonatal respiratory distress is scarcely documented. A term neonate who presented with early onset respiratory distress with a radiographic appearance of an aspiration syndrome is therefore reported. Differential diagnosis and implication of this diagnosis in the management of neonatal respiratory distress are discussed. This case highlights amniotic fluid aspiration as a possible cause of severe respiratory distress even in the absence of meconium stained fluid.


Measurement of 2,6-diamino-4-hydroxy-5-formamidopyrimidine and 8-oxo-7,8-dihydroguanine in isolated DNA exposed to gamma radiation in aqueous solution.
Hydroxyl radical-mediated modifications of nucleobases are among the main deleterious processes induced in DNA by ionizing radiation. Determination of the underlying mechanisms in both isolated and cellular DNA requires the development of accurate assays for the detection of modified bases. High-performance liquid chromatography associated with electrochemical detection (HPLC-EC) and gas chromatography coupled to mass spectrometry (GC-MS) are the two main methods used for this purpose. In the present work, HPLC-EC was applied to the measurement of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) following enzymatic digestion of DNA. Evidence was provided for the quantitative aspect of the latter step. Moreover, a GC-MS assay was designed for the detection of 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua). It was first shown that the widely used hot formic acid hydrolysis of DNA induced a complete decomposition of the lesion. A similar observation was also made for 4,6-diamino-5-formamidopyrimidine (FapyAde). A milder DNA hydrolyzing agent, HF in pyridine, was substituted to HCOOH for the quantitative release of FapyGua from DNA. The radiation-induced formation of 8-oxodGuo and FapyGua in aqueous solution of DNA was compared. Insights in the mechanistic aspects were inferred from the results of gamma-irradiation studies carried out under different gas saturating conditions. It was clearly shown that the formation of both lesions is mediated by HO.. In addition, the presence of oxygen favors the formation of 8-oxodGuo at the expense of FapyGua.


[Mortality and preoperative left ventricular function in aortocoronary bypass surgery (author's transl)].
Left ventricular function in 8 patients with coronary heart disease, who died during or immediately after surgery, was compared with the corresponding data of 25 survivors. Both groups were similar in age and had about the same number of myocardial infarctions preoperatively. For LVEDP, EDV, EF and VCF critical values could be defined, which were found in none of the survivors. These values were: LVDEP approximately 20 mm Hg, EDV approximately 150 ml/m2, EF less than 30% and VCF less than 0,4 circ/s. The least prognostic significance was found for LVEDP; EDV and VCF correlated best with the surgical risk.


Electrical and autonomic cardiac function in patients with Dravet syndrome.
Dravet syndrome (DS) is an epileptic encephalopathy related mainly to mutations in the SCN1A gene, encoding for neuronal sodium channels. Patients with DS have a high risk of sudden unexpected death in epilepsy (SUDEP). In this study we investigated whether patients with DS present abnormalities in electrical and autonomic cardiac function. To this aim we assessed ventricular repolarization and heart rate variability (HRV) on standard electrocardiography (ECG) and on 24-h ECG Holter monitoring, respectively, in 20 patients affected by DS (6.8 ± 4 years, 11 female). As age- and sex-matched control groups, we also studied 20 patients with other epileptic syndromes receiving antiepileptic drugs (ES/AED, 6.0 ± 5 years, 12 female), 20 patients with other epileptic syndromes without treatment (ES/no-AED, 6.7 ± 4 years, 10 female), and 20 healthy children (HC, 7.2 ± 5 years, 11 females). Data analysis showed that patients with DS had depressed HRV variables compared to both ES patients (ES/AED and ES/no-AED) and HC control group, whereas no significant differences in HRV variables were found between ES patients (with and without treatment) and HC. There was no significant difference between patients with DS and all the other control groups in RR intervals, QT, and QTc interval analysis. In conclusion, DS patients display an imbalance of cardiac autonomic function toward a relative predominance of adrenergic tone compared to both healthy children and patients with other forms of epilepsy, independent of antiepileptic therapy. Follow-up studies should clarify the clinical significance of this autonomic impairment and whether HRV analysis can be helpful in predicting the risk of sudden death in patients with DS.


The Effect of CASA on Child Welfare Permanency Outcomes.
The present study is the largest and most rigorous study to date on the effects of being appointed a Court Appointed Special Advocate (CASA) on permanency outcomes of children in foster care. The intent-to-treat study accounts for selection bias by applying inverse probability weighting to logistic and sequential logistic regressions in a large sample of children in foster care in the state of Texas (N = 31,754). Overall, children appointed a CASA have significantly lower odds than children without a CASA of achieving permanency. They have lower odds of being reunified, greater odds of being adopted (if not reunified), and lower odds of being placed in permanent kin guardianship (if not reunified or adopted) than children who are not appointed CASA. This study makes an additional contribution by looking beyond the aggregate effect of CASA on permanency by examining the effect of CASA for different age groups and different types of first placement after removal.


Size Aftereffects Are Eliminated When Adaptor Stimuli Are Prevented from Reaching Awareness by Continuous Flash Suppression.
Size aftereffects are a compelling perceptual phenomenon in which we perceive the size of a stimulus as being different than it actually is following a period of visual stimulation of an adapter stimulus with a different size. Here, we used continuous flash suppression (CFS) to determine if size aftereffects require a high-level appraisal of the adapter stimulus. The strength of size aftereffects was quantified following a 3-s exposure to perceptually visible and invisible adapters. Participants judged the size of a target that followed the adapter in comparison to a subsequent reference. Our experiments demonstrate that the adapter no longer influenced the perceived size of the subsequent target stimulus under CFS. We conclude that the perception of size aftereffects is prevented when CFS is used to suppress the conscious awarness of the adapting stimulus.


Single-molecule experiments to elucidate the minimal requirement for DNA recognition by transcription factor epitopes.
Interactions between proteins and DNA are essential for the regulation of cellular processes in all living organisms. In this context, it is of special interest to investigate the sequence-specific molecular recognition between transcription factors and their cognate DNA sequences. As a model system, peptide and protein epitopes of the DNA-binding domain (DBD) of the transcription factor PhoB from Escherichia coli are analyzed with respect to DNA binding at the single-molecule level. Peptides representing the amphiphilic recognition helix of the PhoB DBD (amino acids 190-209) are chemically synthesized and C-terminally modified with a linker for atomic force microscopy-dynamic force spectroscopy experiments (AFM-DFS). For comparison, the entire PhoB DBD is overexpressed in E. coli and purified using an intein-mediated protein purification method. To facilitate immobilization for AFM-DFS experiments, an additional cysteine residue is ligated to the protein. Quantitative AFM-DFS analysis proves the specificity of the interaction and yields force-related properties and kinetic data, such as thermal dissociation rate constants. An alanine scan for strategic residues in both peptide and protein sequences is performed to reveal the contributions of single amino acid residues to the molecular-recognition process. Additionally, DNA binding is substantiated by electrophoretic mobility-shift experiments. Structural differences of the peptides, proteins, and DNA upon complex formation are analyzed by circular dichroism spectroscopy. This combination of techniques eventually provides a concise picture of the contribution of epitopes or single amino acids in PhoB to DNA binding.


Carbon monoxide concentrations in Santiago City at street levels and their vertical gradient.
Carbon monoxide concentrations were measured at ground level (1 m) near heavy traffic streets in downtown Santiago de Chile in periods of low (November and December), intermediate (April) and high (May) ambient concentrations. Also, measurements were carried out at several heights (from 1 to 127 m) in Santiago's main street during winter time. Measurements carried out at ground level show maximum values during the morning rush hour, with values considerably higher than those reported by the urban air quality network, particularly in summer time. However, the measured values are below air quality standards. Vertical CO profiles were measured in a tower located in the center of downtown. Below 40 m (average altitude of neighboring buildings), the profiles do not show a consistent vertical gradient, with CO concentrations increasing or decreasing with height, regardless of atmospheric stability. In this low altitude range, the observed vertical profiles are poorly predicted by a street canyon model, and the measured concentrations can not be described by a simple exponential decay. At higher altitudes (40 and 127 m) a negative gradient in CO concentrations is observed, both for stable and unstable atmospheric conditions. The values of CO measured at 127 m are relatively well described by an Eulerian dispersion model running with current CO emission inventories for Santiago, although this model tends to predict stepper CO gradients than the observed ones.


A scoping review of patient self-report measures of flare in knee and hip osteoarthritis (OA): A report from the OMERACT flares in OA working group.
We aimed to analyze the content validity/domain match and feasibility of self-report instruments that could measure flare in osteoarthritis (OA), by extending our 2017 literature review on the definition of flare in knee and hip OA. We searched PubMed (Medline), Web of Science and PsycInfo (Ebsco Host) databases for original articles reporting research about flare (or synonyms) in humans with knee and hip OA, between 2017 and 2023. Four experts worked independently, checking the records, and assessing content validity and feasibility, writing justification for exclusion. At literature review phase, 575 papers were filtered. After experts' analysis, 59 studies were included, and 44 instruments associated with flare in OA were identified. Most were studies about pain in knee or hip OA (35 %), cultural adaptation of a measure (33 %) or studies investigating psychometric properties of full (16 %) or short form (4 %) instruments. The assessment of domain match and feasibility revealed that 15 instruments were assigned a label of 'yes' or 'uncertain' as to whether or not there was a good match with the domain concept or whether the instrument was considered feasible to use. Most identified instruments considered different aspects of pain and the associated discomfort in performing daily activities but did not include the central aspects of flare in OA, i.e. the change of state, nor the additional Outcome Measures in Rheumatology (OMERACT) endorsed domains for OA flare namely stiffness, swelling, psychological aspects, impact of symptoms including fatigue and sleep disturbance. Although it is possible that the period specified to conduct this literature review may have led to some recognized instruments being excluded, this review demonstrates the need for the research community to reach consensus on the best way to measure self-reported flares in future clinical trials and observational studies.


The mouse lymph node homing receptor is identical with the lymphocyte cell surface marker Ly-22: role of the EGF domain in endothelial binding.
The lymph node homing receptor core polypeptide (mLHRc) is composed of a tandem collection of domains: a lectin domain, an epidermal growth factor (EGF) domain, and two repeats common in complement regulatory proteins. Here we demonstrate localization of mLHRc to chromosome 1, the portion syntenic with chromosome 1 in man. This locus is inseparable in mouse strains from the murine lymphocyte cell surface marker Ly-22. The data indicate that Ly-22 is an allelic determinant on the LHR resulting from a single amino acid interchange within the EGF domain. Cross-blocking experiments demonstrate that anti-Ly-22 and MEL-14 recognize independent epitopes and that Ly-22 is distinct from the carbohydrate binding region. Application of anti-Ly-22 in the in vitro binding assay shows inhibition of binding of lymphocytes to high endothelial venules (HEVs). The localization of the Ly-22 epitope in this novel chimeric protein suggests direct participation of the EGF domain in the adhesion of lymphocytes to HEV.


TRAPPC9-Related Intellectual Disability: Report of Two New Cases and Review of the Literature.
Hereditary forms of intellectual disability (ID), an estimated prevalence ranging between 1% and 3% in the general population, are among the most important problems in health care. Especially, autosomal-recessive ID has a very heterogeneous molecular basis and a lack of specific phenotypic features. Here, we report on two unrelated patients with autosomal-recessive ID, microcephaly, and autistic features and review the patients with TRAPPC9-related ID. Whole-exome sequencing and array CGH were performed for molecular diagnosis of the patients. The first case has a microdeletion on chromosome 8q24.23-q24.3 region which is 1.7 Mb in length and includes the last 5 exons of TRAPPC9, and c.3435delG [p.Thr1146Profs*8] deletion. The second case has a homozygous missense c.623A>C (p.His208Pro) variant in TRAPPC9 which is detected by means of whole-exome sequencing study of the proband. We also reviewed the clinical findings and mutation spectrum of all patients with TRAPPC9-related ID reported so far. Our study showed that the most consistent clinical findings for TRAPPC9-related ID are ID, microcephaly, and some structural brain MRI abnormalities. The mutations in the TRAPPC9 are scattered throughout all exons of TRAPPC9 indicating there is no hot spot mutation region in this gene.


Fossil actinomycetes in middle precambrian glacial varves.
Fossil actinomycetes and other bacteria have been found in sulfide minerals from "varved" argillites in the middle Precambrian Cobalt Series of Canada. The fossils consist of branched and unbranched nonseptate hyphae and chains of rod-shaped cells. The presence of actinomycetes is consistent with the theory that the argillites are lacustrine desposits.


Scanner Agnostic Ultrasound Image Interpretation.
Ultrasound scanners image the anatomy modulated by their characteristic texture. For certain anatomical regions such as the liver, the characteristic texture of the scanner itself becomes the anatomical marker. Deep Learning (DL) models trained on a scanner-type not only model the anatomical content, they also learn the scanner's characteristic texture. Portability of such models across scanner-types is affected by the learnt styles and results in suboptimal outcome (e.g., for segmentation models, lower Dice values when inferred on images procured from different scanner-type). Instead of retraining the DL model to accommodate this diversity, we transform the texture of the previously unseen data to match the training distribution. Neural style transfer in prior art has used features from the popular VGG network to accomplish this. We not only use a previously trained DL model for the image interpretation task e.g. segmentation, we also utilize its feature maps to accomplish style transfer as well, reducing the complexity of the algorithm pipeline. We demonstrate the improvement in segmentation outcome after such a such style transfer without retraining an existing model.


Tree growth inference and prediction from diameter censuses and ring widths.
Estimation of tree growth is based on sparse observations of tree diameter, ring widths, or increments read from a dendrometer. From annual measurements on a few trees (e.g., increment cores) or sporadic measurements from many trees (e.g., diameter censuses on mapped plots), relationships with resources, tree size, and climate are extrapolated to whole stands. There has been no way to formally integrate different types of data and problems of estimation that result from (1) multiple sources of observation error, which frequently result in impossible estimates of negative growth, (2) the fact that data are typically sparse (a few trees or a few years), whereas inference is needed broadly (many trees over many years), (3) the fact that some unknown fraction of the variance is shared across the population, and (4) the fact that growth rates of trees within competing stands are not independent. We develop a hierarchical Bayes state space model for tree growth that addresses all of these challenges, allowing for formal inference that is consistent with the available data and the assumption that growth is nonnegative. Prediction follows directly, incorporating the full uncertainty from inference with scenarios for "filling the gaps" for past growth rates and for future conditions affecting growth. An example involving multiple species and multiple stands with tree-ring data and up to 14 years of tree census data illustrates how different levels of information at the tree and stand level contribute to inference and prediction.


PD-L1 in small bowel adenocarcinoma is associated with etiology and tumor-infiltrating lymphocytes, in addition to microsatellite instability.
Small bowel adenocarcinomas (SBAs) are often associated with poor prognosis and have limited therapeutic options. Programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway blockade is an effective treatment in many microsatellite instability-high (MSI-H) solid tumors. We aimed at investigating PD-L1 and PD-1 expression in non-hereditary, non-ampullary SBAs, associated with celiac disease (CeD), Crohn's disease (CrD), or sporadic, recruited through the Small Bowel Cancer Italian Consortium. We assessed PD-L1 and PD-1 by immunohistochemistry in a series of 121 surgically resected SBAs, including 34 CeD-SBAs, 49 CrD-SBAs, and 38 sporadic SBAs. PD-L1 and PD-1 expression was correlated with several clinico-pathological features, such as the etiology, microsatellite instability status, and tumor-infiltrating lymphocyte (TIL) density. The prevalence of PD-L1 positivity according to combined positive score (CPS) was 26% in the whole cohort of SBAs, with significantly (p = 0.001) higher percentage (35%) in both CeD-SBAs and CrD-SBAs in comparison with sporadic SBAs (5%). CPS ≥ 1 SBAs were significantly (p = 0.013) more frequent in MSI-H cases (41%) than in non-MSI-H ones (18%); however, 15 CPS ≥ 1 microsatellite stable SBAs were also identified. CPS ≥ 1 SBAs showed higher TIL and PD-1+ immune cell density, more frequently medullary histotype, as well as a better outcome in comparison with CPS < 1 cases. This study demonstrates an increased proportion of PD-L1+ cases in both CeD-SBAs and CrD-SBAs in comparison with sporadic SBAs. In addition, the identification of a subset of PD-L1+ microsatellite stable SBAs supports the need to ascertain additional biomarkers of response to immune checkpoint inhibitors along with MSI-H.


Naringin protects against kainic acid-induced status epilepticus in rats: evidence for an antioxidant, anti-inflammatory and neuroprotective intervention.
The effect of naringin, a bioflavanoid, with potent antioxidant activity was studied on kainic acid (KA)-induced seizures, cognitive deficit and oxidative stress. Rats were administered KA (10 mg/kg intraperitoneally (i.p.)) and observed for behavioral changes and incidence and latency of convulsions over 4 h. The rats were thereafter sacrificed and oxidative stress parameters like malondialdehyde (MDA) and glutathione (GSH) were estimated in the brain. The level of proinflammatory cytokine, tumor necrosis factor (TNF)-α was also determined in the rat brain. It was observed that pretreatment with naringin (20, 40, 80 mg/kg, i.p.) significantly (p<0.001) increased the latency of seizures as compared to the vehicle treated-KA group. Naringin (40, 80 mg/kg) also significantly prevented the increase in MDA and fall in GSH levels due to KA. In addition, naringin dose-dependently attenuated the KA-induced increase in the TNF-α levels of brain. The pretreatment with naringin also significantly increased retention latency in the passive avoidance task. This shows that naringin reduced the cognitive deficit induced by KA. The results of our study suggest that naringin has therapeutic potential since it suppresses KA-induced seizures, cognitive impairment and oxidative stress in the brain. These neuroprotective effects are a result of its antioxidant and anti-inflammatory activity.


Recovery time and heart rate variability following extreme endurance exercise in healthy women.
The relationship between autonomic function and recovery following prolonged arduous exercise in women has not been examined. We undertook an exploratory study that aimed to examine the temporal change in linear and nonlinear measures of heart rate variability (HRV) following prolonged arduous exercise in the form of first all-female (mean age 32.7 ± 3.1 years) team to attempt an unassisted Antarctic traverse. HRV analysis was performed before and 1, 4, and 15 days postexpedition. The traverse was completed in 61 days. There was a significant paired reduction in heart rate, LnLF, LF:HF, DFAα1 between baseline and 15 days postexercise in the same environment. Conversely, RMSSD, LnHF and HFnu, SD1:SD2, and SampEn significantly increased. DFAα2 levels significantly fell from baseline to Day 1 postexercise. In conclusion, we observed a significant latent increase in relative parasympathetic dominance and RR interval irregularity at 15 days post prolonged arduous exercise, versus pre-exercise baseline, in a group of very fit and healthy adult women.


Nontuberculous mycobacterial (NTM) infections in bronchiectasis patients: A retrospective US registry cohort study.
Longitudinal epidemiological and clinical data are needed to improve the management of patients with bronchiectasis developing nontuberculous mycobacterial (NTM) pulmonary disease. To describe the epidemiology, patient management, and treatment outcomes of NTM infections in patients with bronchiectasis enrolled in the United States Bronchiectasis and NTM Research Registry (US BRR). This was a retrospective cohort study of patients with bronchiectasis and NTM infections enrolled with follow-up in the US BRR in 2008-2019. The study included patients with ≥1 positive NTM respiratory culture in the 24-month baseline period (baseline NTM cohort) and/or during the annual follow-up visits (incident NTM cohort). Incidence, prevalence, baseline patient characteristics, treatment exposure, treatment outcomes, and respiratory clinical outcomes were described in the baseline NTM cohort, incident NTM cohort, and both cohorts combined (prevalent NTM cohort). Between 2008 and 2019, 37.9% (1457/3840) of patients with bronchiectasis in the US BRR met the inclusion criteria for this study and were reported to have Mycobacterium avium complex (MAC) and/or Mycobacterium abscessus complex (MABSC) infections. MAC prevalence increased steadily in the US BRR during 2009-2019; incidence was relatively stable, except for a peak in 2011 followed by a slow decrease. MABSC and mixed MAC/MABSC infections were rare. Most patients with bronchiectasis and NTM infections in the registry were female, White, and aged >65 years. The antibiotics administered most commonly reflected current guidelines. In the prevalent cohort, 44.9% of MAC infections and 37.1% of MABSC infections remained untreated during follow-up, and MAC treatment was initiated with delay (>90 days after positive NTM respiratory culture) twice as frequently as promptly (≤90 days after positive NTM respiratory culture) (68.6% vs 31.4%, respectively). The median time from diagnosis to treatment was shorter for MABSC versus MAC infections (194.0 days [interquartile range (IQR) 8.0, 380.0] vs 296.0 days [IQR 35.0, 705.0], respectively). Among patients with MAC infections who completed treatment, 27.6% were classified as cured and 29.6% as treatment failure during the annual follow-up visit window. For MABSC, these proportions were 25.0% and 28.0%, respectively. A considerable proportion of MAC and MABSC infections were untreated or treated after initial delay/observation. MABSC infections were more likely to be treated and start treatment sooner than MAC infections. Further longitudinal studies are warranted to evaluate the monitor-with-delay approach and inform clinical guidelines.


Importance of Enhanced Surveillance for Prevention of Pertussis in Children.
Bordetella pertussis infection causes considerable morbidity, even in countries with high vaccination coverage. Surveillance of pertussis is usually passive and based on mandatory reporting. We assessed the epidemiologic and clinical characteristics of pertussis cases detected by passive or enhanced surveillance. A prospective population-based study was carried out from January 2012 to December 2013 in Catalonia and Navarre, 2 Spanish regions with a total population of 8.2 million. For each confirmed case, variables of age, sex, clinical symptoms, laboratory results and vaccination status were investigated. Associations between the variables studied and the type of surveillance were assessed by odds ratio (OR) and its 95% confidence interval (CI). Logistic regression was used to estimate adjusted OR (aOR). In children <18 years of age, passive surveillance was the most important source of detection (95.7% in <1 year). In children 5-10 years of age, passive surveillance detected 67.5% of cases. In those ≥18 years, enhanced surveillance was the most frequent source of case detection (82.5%). Inspiratory whoop (aOR: 1.94; 95% CI: 1.40-2.70), apnea (aOR: 1.92; 95% CI: 1.28-2.87) and posttussive vomiting (aOR: 1.43; 95% CI: 1.04-1.96) were symptoms included in the clinical case definition that were associated with passive surveillance. Underreporting of symptomatic cases is important not only in adults, but also in children >1 year of age and suggests that providing clinics with free, fast laboratory diagnostic tests, together with enhanced surveillance of family contacts of any age is necessary to better determine existing cases. Enhanced surveillance may be helpful to better understand transmission patterns in the family and in the community.


Examining the coupling of carbon and nitrogen cycles in Appalachian streams: the role of dissolved organic nitrogen.
Although regional and global models of nitrogen (N) cycling typically focus on nitrate, dissolved organic nitrogen (DON) is the dominant form of nitrogen export from many watersheds and thus the dominant form of dissolved N in many streams. Our understanding of the processes controlling DON export from temperate forests is poor. In pristine systems, where biological N limitation is common, N contained in recalcitrant organic matter (OM) can dominate watershed N losses. This recalcitrant OM often has moderately constrained carbon:nitrogen (C:N) molar ratios (approximately 25-55) and therefore, greater DON losses should be observed in sites where there is greater total dissolved organic carbon (DOC) loss. In regions where anthropogenic N pollution is high, it has been suggested that increased inorganic N availability can reduce biological demand for organic N and therefore increase watershed DON losses. This would result in a positive correlation between inorganic and organic N concentrations across sites with varying N availability. In four repeated synoptic surveys of stream water chemistry from forested watersheds along an N loading gradient in the southern Appalachians, we found surprisingly little correlation between DON and DOC concentrations. Further, we found that DON concentrations were always significantly correlated with watershed N loading and stream water [NO3-] but that the direction of this relationship was negative in three of the four surveys. The C:N molar ratio of dissolved organic matter (DOM) in streams draining watersheds with high N deposition was very high relative to other freshwaters. This finding, together with results from bioavailability assays in which we directly manipulated C and N availabilities, suggests that heterotrophic demand for labile C can increase as a result of dissolved inorganic N (DIN) loading, and that heterotrophs can preferentially remove N-rich molecules from DOM. These results are inconsistent with the two prevailing hypotheses that dominate interpretations of watershed DON loss. Therefore, we propose a new hypothesis, the indirect carbon control hypothesis, which recognizes that heterotrophic demand for N-rich DOM can keep stream water DON concentrations low when N is not limiting and heterotrophic demand for labile C is high.


[beta-blocker in hypertension].
The beta-blockers are either nonselective and affect both beta 1- and beta 2-receptors, are relatively selective for the alpha 1 subclass, or are able to have activity against alpha-receptors. The ability to reduce blood pressure is very common among all beta-blockers, and beta-blockers are recommended for one of the first-line drugs in hypertension treatment by JNCV. beta-blockers should be used considering their pharmacological properties and potential side effects, according to the pathophysiological conditions involved. The superiority of beta-blocker to other types of antihypertensive drug has not yet been evidenced by larger scale clinical trials which have been carried out so far. To verify more precisely the usefulness of beta-blocker in hypertension treatment, more large scale clinical trials are required to be carried out. The fixed-dose combination of beta-blockers and calcium blockers appears to be more effective rather than that of beta-blockers and diuretics.


The underdiagnosis of cannabis use disorders and other Axis-I disorders among military veterans within VHA.
Recent evidence suggests that rates of cannabis use disorders are significantly lower among military veterans within the Veterans Affairs Health Care System (VA) than the general U.S. population. However, prevalence rates obtained from the VA rely on clinician diagnosis, which have been shown to be underrepresentative of actual disorder rates. The present study utilized structured clinical interviews to assess a sample of 84 military veterans with a cannabis use disorder and compared Axis-I disorder diagnosis rates to those obtained through a retrospective electronic medical record chart review. Findings indicated that cannabis use disorders, as well as posttraumatic stress disorder and other anxiety disorders, were significantly underdiagnosed within this military veteran population. In contrast, rates of other substance use disorders as well as mood disorders were overdiagnosed within this VA population. Findings are discussed in relation to the improvement of screening and repeated structured assessment of military veterans within the VA.


A simple electrochemical platform based on pectin stabilized gold nanoparticles for picomolar detection of biologically toxic amitrole.
Amitrole is a biologically toxic nonselective herbicide which contaminates surface and ground waters at unprecedented rates. All reported modified electrodes that detect amitrole within sub-micromolar to nanomolar levels were based on the electro-oxidation of amitrole. Herein, we developed a new conceptual idea to detect picomolar concentrations of amitrole based on calcium cross linked pectin stabilized gold nanoparticle (CCLP-GNP) film modified electrode which was prepared by electrodeposition. When the electrochemical behavior of amitrole was investigated at the CCLP-GNP film, the reduction peak current of the GNPs linearly decreased as the concentration of amitrole increases. We have designed a determination platform based on the amitrole dependent decrease of the GNP cathodic peak. The described concept and high sensitivity of square wave voltammetry together facilitate the great sensing ability; as a result the described approach is able to reach a low detection limit of 36 pM which surpassed the detection limits of existing protocols. The sensor presents a good ability to determine amitrole in two linear concentration ranges: (1) 100 pM-1500 pM with a detection limit of 36 pM; (2) 100 nM-1500 nM with a detection limit of 20 nM. The preparation of CCLP-GNPs is simple, rapid and does not require any reducing agents.


Opening to the sacred: intentional use of music to engage the spiritual dimension.
Music is a patterned temporal art characterized by its pulse, rhythm, and melody. It can be intentionally used as a vehicle or gateway to the nonrational as contrasted to an irrational dimension of human experience. This realm of experience frequently provides access to the sacred. The indissoluble unity of body-mind-spirit has been a tenet of creative artists for centuries, and is now gaining the attention of health care professionals. This article explores the conceptual and applied potential of integrating music as a spiritual practice in skilled and compassionate health and illness care.


Broadband frequency mode entanglement in waveguided parametric downconversion.
We report the observation of beatings of the coincidence event rate in a Hong-Ou-Mandel interference (HOMI) between signal and idler photons from a parametric downconversion (PDC) process inside a multimode KTP waveguide. As an explanation we introduce biphotonic states entangled in their broadband frequency modes generated by waveguide mode triples and propose a suitable entanglement detection scheme.


Attribute vector guided groupwise registration.
Groupwise registration has been recently introduced to simultaneously register a group of images by avoiding the selection of a particular template. To achieve this, several methods have been proposed to take advantage of information-theoretic entropy measures based on image intensity. However, simplistic utilization of voxelwise image intensity is not sufficient to establish reliable correspondences, since it lacks important contextual information. Therefore, we explore the notion of attribute vector as the voxel signature, instead of image intensity, to guide the correspondence detection in groupwise registration. In particular, for each voxel, the attribute vector is computed from its multi-scale neighborhoods, in order to capture the geometric information at different scales. The probability density function (PDF) of each element in the attribute vector is then estimated from the local neighborhood, providing a statistical summary of the underlying anatomical structure in that local pattern. Eventually, with the help of Jensen-Shannon (JS) divergence, a group of subjects can be aligned simultaneously by minimizing the sum of JS divergences across the image domain and all attributes. We have employed our groupwise registration algorithm on both real (NIREP NA0 data set) and simulated data (12 pairs of normal control and simulated atrophic data set). The experimental results demonstrate that our method yields better registration accuracy, compared with a popular groupwise registration method.


[Laparoscopic management of ureteroileal stenosis: Long term follow up.]
To describe the laparoscopic approach for uretero-ileal anastomosis strictures and to analyse our long term series. A retrospective review was performed evaluating our series of patients with benign ureteroileal anastomosis strictures treated laparoscopically from 2011 to 2017. Demographics and perioperative data were obtained and analyzed. Complications were described with the Clavien-Dindo classification. The surgical technique was described and a literature review was performed. Eleven procedures were performed in ten patients. Mean blood loss was 180 ml. All the operations were performed laparoscopically without conversion. Mean hospital stay was 10 days (4-23). Early complications were Clavien-Dindo I y II: Two cases of limited anastomosis leakage, one lymphorrea, one paralitic ileum and one accidental descent of the ureteral catheter. Mean follow-up was 56 months (12-179) No late complications have been described. Based on our series with 5 year follow up, the laparoscopic approach for uretero-ileal anastomosis strictures is feasible and safe.


[Retrospective study on cancer of the base of the tongue].
From Feb. 1962 to Feb. 1982, 54 patients with cancer of the base of tongue were treated in our hospital. There were 44 squamous cell carcinomas and 10 adeno-cystic carcinomas. 46 patients were treated by radiotherapy only, 6 by surgery plus radiotherapy, 1 by surgery and 1 by chemotherapy alone. The 5 year survival rate was 27.1%. The result indicates that radiotherapy alone is poor. The author suggests that for cancer of the base of tongue, a combination of radiotherapy and surgery be used and prospective randomized study be carried out. The defect can be repaired using skin or myocutaneous flaps. In extensive lesions, glossectomy plus laryngectomy should be considered. For the healthy and young patients, the lesions of the base of tongue together with a part of the larynx should be extirpated but for the older man, selective glossectomy is advised.


Influence of age on operative mortality and long-term survival after lung resection for bronchogenic carcinoma.
The proportion of elderly patients presenting with bronchogenic carcinoma is increasing. To study the impact of age on clinical presentation, management and outcome of patients, the authors have reviewed their clinical experience over the last 20 yrs. Between 1977 and 1996, 1,079 patients underwent thoracotomy for primary lung carcinoma in the authors' institution. Patients were grouped by age at the time of surgery as <60 yrs, 60-69 yrs and > or =70 yrs. Although the mode of clinical presentation was similar between all age groups, patients <60 yrs were more prone to have advanced stage carcinoma at the time of diagnosis. The rates of exploratory thoracotomy and pneumonectomy were higher in patients <70 yrs, whereas lobectomies and lesser resections largely predominated in patients > or =70 yrs. The mortality rate following lobectomy and lesser resection increased from 1.3% in patients <60 yrs to 5.5% in patients > or =60 yrs (p=0.04) and the mortality rate following pneumonectomy increased from 6.5% in patients <60 yrs to 13.7% in patients > or =70 yrs (p=0.24). The specific long-term survival, which included only the patients who died from primary lung carcinoma, was similar in all age groups. Operative mortality and survival rates are acceptable in patients > or =70 yrs. Therefore, age in itself should not constitute a contraindication to surgical lung resection for primary lung carcinoma as long as a careful preoperative assessment is performed to appropriately select surgical candidates.


A High-Quality Genome Assembly of the North American Song Sparrow, Melospiza melodia.
The song sparrow, Melospiza melodia, is one of the most widely distributed species of songbirds found in North America. It has been used in a wide range of behavioral and ecological studies. This species' pronounced morphological and behavioral diversity across populations makes it a favorable candidate in several areas of biomedical research. We have generated a high-quality de novo genome assembly of M. melodia using Illumina short read sequences from genomic and in vitro proximity-ligation libraries. The assembled genome is 978.3 Mb, with a physical coverage of 24.9×, N50 scaffold size of 5.6 Mb and N50 contig size of 31.7 Kb. Our genome assembly is highly complete, with 87.5% full-length genes present out of a set of 4,915 universal single-copy orthologs present in most avian genomes. We annotated our genome assembly and constructed 15,086 gene models, a majority of which have high homology to related birds, Taeniopygia guttata and Junco hyemalis In total, 83% of the annotated genes are assigned with putative functions. Furthermore, only ∼7% of the genome is found to be repetitive; these regions and other non-coding functional regions are also identified. The high-quality M. melodia genome assembly and annotations we report will serve as a valuable resource for facilitating studies on genome structure and evolution that can contribute to biomedical research and serve as a reference in population genomic and comparative genomic studies of closely related species.


Human and Algorithmic Predictions in Geopolitical Forecasting: Quantifying Uncertainty in Hard-to-Quantify Domains.
Research on clinical versus statistical prediction has demonstrated that algorithms make more accurate predictions than humans in many domains. Geopolitical forecasting is an algorithm-unfriendly domain, with hard-to-quantify data and elusive reference classes that make predictive model-building difficult. Furthermore, the stakes can be high, with missed forecasts leading to mass-casualty consequences. For these reasons, geopolitical forecasting is typically done by humans, even though algorithms play important roles. They are essential as aggregators of crowd wisdom, as frameworks to partition human forecasting variance, and as inputs to hybrid forecasting models. Algorithms are extremely important in this domain. We doubt that humans will relinquish control to algorithms anytime soon-nor do we think they should. However, the accuracy of forecasts will greatly improve if humans are aided by algorithms.


Neurohumoral, hemodynamic and microvascular changes as mechanisms of insulin resistance in hypertension: a provocative but partial picture.
Hyperinsulinemia and insulin resistance are largely explained by upper body obesity in hypertension. However, non-obese hypertensive patients have similar metabolic defects. Thus, neurohumoral, hemodynamic, and microvascular abnormalities which occur in the development of hypertension may contribute to insulin resistance independent of obesity. Sympathetic drive and vascular alpha-tone are increased in young, predominantly overweight patients with borderline-mild hypertension. The importance of increased neurogenic tone, especially the alpha-adrenergic component, is emphasized by evidence that alpha 1-receptor antagonists virtually normalize insulin metabolism in hypertensive patients. Patients with mild hypertension have elevated forearm vascular resistance which could theoretically contribute to insulin resistance by impairing muscle perfusion. However, blood flow is normal at baseline and maximal dilation. Similarly, overweight young men have hyperinsulinemia, despite higher basal forearm blood flow and a normal vasodilator reserve. Thus, insulin resistance is not uniformly determined by basal blood flow or flow reserve. However, defects in regional flow distribution or in dynamic flow responses may alter insulin action. Microvascular rarefaction may contribute to insulin resistance in hypertensive patients by increasing diffusion distance for insulin to sites of action. The independent role of capillary density is unknown, since it correlates with muscle fiber type. Furthermore, in the absence of significant kinetic differences for insulin's multiple actions in skeletal muscle, structural vascular abnormalities would likely cause global defects rather than specific abnormalities in non-oxidative glucose disposal. Theories linking neurohumoral, hemodynamic and microvascular abnormalities in hypertension to insulin resistance are intriguing but unproven. Since insulin resistance has important implications in human disease, further research on mechanisms of this resistance is important.


Brain neurotransmitter transporter/receptor genomics and efavirenz central nervous system adverse events.
We characterized associations between central nervous system (CNS) adverse events and brain neurotransmitter transporter/receptor genomics among participants randomized to efavirenz-containing regimens in AIDS Clinical Trials Group studies in the USA. Four clinical trials randomly assigned treatment-naive participants to efavirenz-containing regimens. Genome-wide genotype and PrediXcan were used to infer gene expression levels in tissues including 10 brain regions. Multivariable regression models stratified by race/ethnicity were adjusted for CYP2B6/CYP2A6 genotypes that predict plasma efavirenz exposure, age, and sex. Combined analyses also adjusted for genetic ancestry. Analyses included 167 cases with grade 2 or greater efavirenz-consistent CNS adverse events within 48 weeks of study entry, and 653 efavirenz-tolerant controls. CYP2B6/CYP2A6 genotype level was independently associated with CNS adverse events (odds ratio: 1.07; P=0.044). Predicted expression of six genes postulated to mediate efavirenz CNS side effects (SLC6A2, SLC6A3, PGR, HTR2A, HTR2B, HTR6) were not associated with CNS adverse events after correcting for multiple testing, the lowest P value being for PGR in hippocampus (P=0.012), nor were polymorphisms in these genes or AR and HTR2C, the lowest P value being for rs12393326 in HTR2C (P=6.7×10(-4)). As a positive control, baseline plasma bilirubin concentration was associated with predicted liver UGT1A1 expression level (P=1.9×10(-27)). Efavirenz-related CNS adverse events were not associated with predicted neurotransmitter transporter/receptor gene expression levels in brain or with polymorphisms in these genes. Variable susceptibility to efavirenz-related CNS adverse events may not be explained by brain neurotransmitter transporter/receptor genomics.


Thymidine kinase 1 deficient cells show increased survival rate after UV-induced DNA damage.
Balanced deoxynucleotide pools are known to be important for correct DNA repair, and deficiency for some of the central enzymes in deoxynucleotide metabolism can cause imbalanced pools, which in turn can lead to mutagenesis and cell death. Here we show that cells deficient for the thymidine salvage enzyme thymidine kinase 1 (TK1) are more resistant to UV-induced DNA damage than TK1 positive cells although they have thymidine triphosphate (dTTP) levels of only half the size of control cells. Our results suggest that higher thymidine levels in the TK- cells caused by defect thymidine salvage to dTTP protects against UV irradiation.


Quantification of vitamin B6 vitamers in human cerebrospinal fluid by ultra performance liquid chromatography-tandem mass spectrometry.
Since vitamin B6 is essential for normal functioning of the central nervous system, there is growing need for sensitive analysis of B6 vitamers in cerebrospinal fluid (CSF). This manuscript describes the development and validation of a rapid, sensitive and accurate method for quantification of the vitamin B6 vitamers pyridoxal (PL), pyridoxamine (PM), pyridoxine (PN), pyridoxic acid (PA), pyridoxal 5'-phosphate (PLP), pyridoxamine 5'-phosphate (PMP) and pyridoxine 5'-phosphate (PNP) in human CSF. The method is based on ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) with a simple sample preparation procedure of protein precipitation using 50 g L(-1) trichloroacetic acid containing stable isotope labeled internal standards: PL-D(3) for PL and PM, PN-(13)C(4) for PN, PA-D(2) for PA and PLP-D(3) for the phosphorylated vitamers. B6 vitamers were separated (Acquity HSS-T3 UPLC column) with a buffer containing acetic acid, heptafluorobutyric acid and acetonitrile. Positive electrospray ionization was used to monitor transitions m/z 168.1→150.1 (PL), 169.1→134.1 (PM), 170.1→134.1 (PN), 184.1→148.1 (PA), 248.1→150.1 (PLP), 249.1→232.1 (PMP) and 250.1→134.1 (PNP). The method was validated at three concentration levels for each B6 vitamer in CSF. Recoveries of the internal standards were between 93% and 96%. Intra- and inter-assay variations were below 20%. Accuracy tests showed deviations from 3% (PN) to 39% (PMP). Limits of quantification were in the range of 0.03-5.37 nM. Poor results were obtained for quantification of PNP. The method was applied to CSF samples of 20 subjects and two patients on pyridoxine supplementation. Using minimal CSF volumes this method is suitable for implementation in a routine diagnostic setting.


[Reactivity of neurons of the orbito-frontal cortex of the cat during exposure to the scent or sight of food].
Reactivity of neurones in orbitofrontal cortex of the cat to the action of light or sound was studied in consecutive stages of alimentary behaviour conditioned by the smell and then the sight of food. Changes were found of the character of neuronal reactions to the light and sound stimuli at the change of smell to the sight of food. A conclusion is drown, that polysensory properties of the neurones of the orbitofrontal cortex provide integral organization of brain sensory function at separate stages of alimentary behaviour.


Withholding versus withdrawing life-sustaining treatment: patient factors and documentation associated with dialysis decisions.
We evaluated prospectively the use of acute hemodialysis among hospitalized patients to identify demographic and clinical predictors of and chart documentation concerning dialysis withheld and withdrawn. Prospective cohort study. Five teaching hospitals. Five hundred sixty-five seriously ill hospitalized patients who had not previously undergone dialysis who developed renal failure. Patient demographics, clinical characteristics, preferences, and prognostic estimates associated with having dialysis withheld rather than initiated and withdrawn rather than continued. Differences in chart documentation concerning decision-making for dialysis withheld, withdrawn, and continued. Older patient age, cancer diagnosis, and male gender were associated with dialysis withheld rather than withdrawn. Age and gender differences persisted after adjustment for patients' aggressiveness of care preference. Worse 2-month prognosis was associated with both withholding and withdrawing dialysis. Chart documentation of decision-making was lacking more often for patients with dialysis withheld than for dialysis withdrawn. Measuring the equity of life-sustaining treatment use will require evaluation of care withheld, not just care withdrawn. Older patients and men, after accounting for prognosis and function, are more likely to have dialysis withheld than withdrawn after a trial. Further exploration is needed into this disparity and the inadequate chart documentation for patients with dialysis withheld.


Protective effect of cardamonin against acetic acid-induced ulcerative colitis in rats.
Ulcerative colitis (UC) is an inflammatory bowel disease with significant morbidity. Cardamonin is a natural chalcone derivative with considerable anti-inflammatory activity. Herein, the potential protective effect of cardamonin against UC was tested in a rat model. Rats were given 10 or 30mg/kg/day of cardamonin orally for 14days before induction of UC. On the 14th day of treatment, UC was induced by intrarectal instillation of 2ml 3% acetic acid. Twenty four h after acetic acid instillation, rats were sacrificed and colons were analyzed by macroscopic and histopathological examination. Colon lipid peroxidation was examined by biochemical evaluation of malondialdehyde (MDA). Myeloperoxidase (MPO), iNOS, NF-κB, TNFα levels were measured by ELISA. Moreover, caspase-3 and COX-2 were assessed by immunohistochemical analysis. Cardamonin at 10 and 30mg/kg decreased the disease activity index and macroscopic damage index scores, and significantly reduced histopathological deterioration. Additionally, cardamonin reduced levels of MPO, iNOS, NF-κB, TNFα and MDA (p<0.05). Immunohistochemistry revealed down-regulation of COX-2 and caspase-3 in groups treated with cardamonin. Cardamonin has a protective effect against acetic acid-induced colitis. This effect may be due to reducing inflammation, oxidative stress and apoptosis.


CD24 promotes the proliferation and inhibits the apoptosis of cervical cancer cells in vitro.
The protein CD24 is a cell surface protein that appears to function as an adhesion molecule; its expression has been shown to correlate with prognosis in a variety of tumors. Herein, we investigated the possible role and mechanism of CD24 in cervical cancer. Our results showed that CD24 was overexpressed in cervical cancer tissues compared with that in the adjacent non‑cancerous tissues by qPCR, immunohistochemistry and western blotting technologies. To explore the possible mechanism of CD24 in cervical cancer, we elucidated the effect of CD24 on the proliferation and apoptosis of cervical cancer HeLa cells and found that a considerable increase in cell proliferation was observed in the HeLa cells with CD24 overexpession. The rate of cell apoptosis was decreased in the HeLa/CD24 cells compared with the HeLa or HeLa/vector cells. Cell apoptosis is closely related with a reduction in mitochondrial membrane potential (ΔΨm) and an increase in intracellular reactive oxygen species (ROS) and calcium ion (Ca2+) concentrations. Our results showed that overexpression of CD24 in the cervical cancer HeLa cells, led to an increase in ΔΨm and a decrease in intracellular ROS and Ca2+ concentrations. Furthermore, we found that CD24 was correlated with dysregulation of the MAPK signaling pathway in cervical cancer tissues in vitro. At the same time, we found that CD24 overexpression affected the expression of p38, JNK2 and c-Jun in vitro. In summary, our results suggest that CD24 is upregulated in cervical cancer tissues and plays its functions by affecting the MAPK signaling pathway in cervical cancer.


Estimating correlation by using a general linear mixed model: evaluation of the relationship between the concentration of HIV-1 RNA in blood and semen.
Estimating the correlation coefficient between two outcome variables is one of the most important aspects of epidemiological and clinical research. A simple Pearson's correlation coefficient method is usually employed when there are complete independent data points for both outcome variables. However, researchers often deal with correlated observations in a longitudinal setting with missing values where a simple Pearson's correlation coefficient method cannot be used. General linear mixed models (GLMM) techniques were used to estimate correlation coefficients in a longitudinal data set with missing values. A random regression mixed model with unstructured covariance matrix was employed to estimate correlation coefficients between concentrations of HIV-1 RNA in blood and seminal plasma. The effects of CD4 count and antiretroviral therapy were also examined. We used data sets from three different centres (650 samples from 238 patients) where blood and seminal plasma HIV-1 RNA concentrations were collected from patients; 137 samples from 90 different patients without antiviral therapy and 513 samples from 148 patients receiving therapy were considered for analysis. We found no significant correlation between blood and semen HIV-1 RNA concentration in the absence of antiviral therapy. However, a moderate correlation between blood and semen HIV-1 RNA was observed among subjects with lower CD4 counts receiving therapy. Our findings confirm and extend the idea that the concentrations of HIV-1 in semen often differ from the HIV-1 concentration in blood. Antiretroviral therapy administered to subjects with low CD4 counts result in sufficient concomitant reduction of HIV-1 in blood and semen so as to improve the correlation between these compartments. These results have important implications for studies related to the sexual transmission of HIV, and development of HIV prevention strategies.


Self-aligning lidar for the continuous monitoring of the atmosphere.
In a lidar system an accurate transmitter-receiver alignment is essential for correct results. Usually this optical adjustment is time consuming and requires the intervention of highly qualified personnel. As a solution to this problem, a fast and precise automatic alignment procedure is presented, based on a simple model of the transmitter-receiver overlap. The lidar mounted at the Naples University is used to test this method. A centering precision of few microradians is obtained through dedicated software controlling a gimbal-mounted mirror. The automatic alignment procedure is then assessed. In particular, the correctness of the center and of its error is determined. Finally, the system is applied to the monitoring of tropospheric aerosols, leading to the continuous retrieval of profiles with fine spatiotemporal resolution.


Cranial nerve injuries are associated with specific craniofacial fractures after blunt trauma.
Identification of cranial nerve (CN) injuries after blunt trauma is often delayed due to concomitant life-threatening trauma, altered mental status, and associated bony or soft tissue injuries. We hypothesized that specific craniofacial fracture (FX) patterns are associated with CN injuries, permitting earlier diagnosis. The trauma registry at a single institution was queried for all CN injuries and craniofacial FXs. Associations were determined by Fisher's exact test. Ninety CN injuries were identified in 59 patients. CN injuries were diagnosed on the day of admission in 24 (41%) patients. The most frequently injured CNs were CN VII (22), CN I (16), and CN VI (14). Occipital FXs were associated with CN I injury (P = 0.001). Sphenoid and ethmoid FXs were correlated with CN III trauma (P = 0.019 and 0.04). Temporal bone FXs were associated with CN VII injuries (P = 0.025). Maxillary FXs were associated with CN V injuries (P = 0.041). Complete or partial recovery was documented after 17 per cent and 39 per cent of CN injuries, respectively. Diagnostic delay was documented in 59 per cent of patients. Specific craniofacial FXs were correlated with certain CN injuries. Partial or complete recovery of function occurred after 56 per cent of CN injuries.


Monoclonal antibodies reacting with multiple epitopes on the human insulin receptor.
Monoclonal antibodies for the human insulin receptor were produced following immunization of mice with IM-9 lymphocytes and/or purified placental receptor. Four separate fusions yielded 28 antibodies, all of which reacted with receptor from human placenta, liver and IM-9 cells. Some antibodies cross-reacted to varying degrees with receptor from rabbit, cow, pig and sheep, but none reacted with rat receptor. At least 10 distinct epitopes were recognized as indicated by species specificity and binding competition experiments. All of these epitopes appeared to be on extracellular domains of the receptor as shown by binding of antibodies to intact cells. In some cases the epitopes were further localized to alpha or beta subunits by immunoblotting. Several antibodies inhibited binding of 125I-insulin to the receptor, some had no effect on binding, and others enhanced the binding of 125I-insulin. It is concluded that these antibodies will be valuable probes of receptor structure and function.


Ventral anterior cingulate connectivity distinguished nonpsychotic bipolar illness from psychotic bipolar disorder and schizophrenia.
Bipolar illness is a debilitating neuropsychiatric disorder associated with alterations in the ventral anterior cingulate cortex (vACC), a brain region thought to regulate emotional behavior. Although recent data-driven functional connectivity studies provide evidence consistent with this possibility, the role of vACC in bipolar illness and its pattern of whole brain connectivity remain unknown. Furthermore, no study has established whether vACC exhibits differential whole brain connectivity in bipolar patients with and without co-occurring psychosis and whether this pattern resembles that found in schizophrenia. We conducted a human resting-state functional connectivity investigation focused on the vACC seed in 73 remitted bipolar I disorder patients (33 with psychosis history), 56 demographically matched healthy comparison subjects, and 73 demographically matched patients with chronic schizophrenia. Psychosis history within the bipolar disorder group corresponded with significant between-group connectivity alterations along the dorsal medial prefrontal surface when using the vACC seed. Patients with psychosis history showed reduced connectivity (Cohen's d = -0.69), whereas those without psychosis history showed increased vACC coupling (Cohen's d = 0.8) relative to controls. The vACC connectivity observed in chronic schizophrenia patients was not significantly different from that seen in bipolar patients with psychosis history but was significantly reduced compared with that in bipolar patients without psychosis history. These robust findings reveal complex vACC connectivity alterations in bipolar illness, which suggest differences depending on co-occurrence of lifetime psychosis. The similarities in vACC connectivity patterns in schizophrenia and psychotic bipolar disorder patients may suggest the existence of common mechanisms underlying psychotic symptoms in the two disorders.


Effect of on-arrival BRD vaccination on ultrasound confirmed pneumonia and production parameters in male dairy calves: a randomized clinical trial.
The high degree of commingling and accumulation of stressors during and after transport makes prevention of bovine respiratory disease (BRD) extremely challenging in the veal and dairy beef industry. Upon arrival, vaccination for agents involved in BRD is practically most achievable, but its efficacy under such conditions in dairy veal calves is unknown. Given the high prevalence of subclinical pneumonia in these settings, the primary objective of the present study was to determine the effect of 2 vaccination protocols administered upon arrival against bovine respiratory syncytial virus (BRSV), bovine parainfluenza type 3 virus (BPI-3) and Mannheimia haemolytica on clinical BRD and lung ultrasonographic findings in dairy veal calves. In addition, the effects of vaccination on average daily live weight gain and cold carcass weight were determined. In this randomized clinical trial, 443 male dairy calves were assigned to one of 3 groups: a negative, placebo-controlled group (NC) (n = 151), a vaccination group with 2 subcutaneous injections 4 weeks apart with an inactivated vaccine containing BRSV, BPI-3 and M. haemolytica (parenteral (PE) group) (n = 149) and a second vaccination group receiving an intranasal live-attenuated vaccine containing BRSV and BPI-3 and 2 subcutaneous vaccinations with the same inactivated vaccine as the PE vaccination group (intranasal-parenteral (IN/PE) group) (n = 143). Clinical scoring and quick thoracic ultrasonography (qTUS) were performed on all calves on arrival (wk 0), at the peak of respiratory disease (outbreak) (wk 1), at the end of the first antimicrobial group treatment (wk 3) and at a long-term evaluation point (wk 10). Culture and nanopore-sequencing on non-endoscopic broncho-alveolar lavage (nBAL) samples were used to identify pathogens involved in the outbreak. Upon arrival, 15.1% of the calves had lung consolidation ≥1cm and incidence quickly rose to 42.8% during the outbreak. In both the PE and IN-PE group, the odds of pneumonia in wk 10 were reduced by 62% (odds ratio (OR) = 0.38; 95% confidence interval (CI) = 0.23-0.64) and 41% (OR = 0.59; 95% CI = 0.37-0.96), respectively. Short-term cure rate (50.3%), as determined immediately after the first group antimicrobial treatment, was not influenced by vaccination. In contrast, long-term cure rate, determined at wk 10, was affected by vaccination with higher cure in the PE group compared with the control group (69.4% vs 51.2%; OR = 2.2; 95% CI = 1.1-5.0). ADG in the first 10 weeks of production was not affected by vaccination. Vaccination resulted in an increase in cold carcass weight of 3.5 and 4.3 kg in the PE (95% CI = -0.9-7.9) and IN-PE group (95% CI = -0.17-8.7), respectively. In conclusion, under the conditions of the present study, vaccination upon arrival resulted in a reduced prevalence of pneumonia at wk 10 of production, likely caused both by an improved cure rate of secondary infections and a reduced incidence of new cases between outbreak and long-term evaluation. The present protocol, using qTUS for pneumonia detection and nBAL diagnostics for pathogen identification adds a new dimension to randomized clinical trials on respiratory disease in calves.


Circumsolar radiation as a measure of the turbidity of the atmosphere. Part 2.
The paper is theoretical, based on experimental data. It treats field measurements of the circumsolar radiation in order to derive from them the variations of the turbidity of the atmosphere at the high level stations Table Mountain and Montezuma. A single relationship is derived for the circumsolar radiation as a function of the coefficient of turbidity beta.


Genomic imprinting-like monoallelic paternal expression determines sex of channel catfish.
The X and Y chromosomes of channel catfish have the same gene contents. Here, we report allelic hypermethylation of the X chromosome within the sex determination region (SDR). Accordingly, the X-borne hydin-1 gene was silenced, whereas the Y-borne hydin-1 gene was expressed, making monoallelic expression of hydin-1 responsible for sex determination, much like genomic imprinting. Treatment with a methylation inhibitor, 5-aza-dC, erased the epigenetic marks within the SDR and caused sex reversal of genetic females into phenotypic males. After the treatment, hydin-1 and six other genes related to cell cycle control and proliferative growth were up-regulated, while three genes related to female sex differentiation were down-regulated in genetic females, providing additional support for epigenetic sex determination in catfish. This mechanism of sex determination provides insights into the plasticity of genetic sex determination in lower vertebrates and its connection with temperature sex determination where DNA methylation is broadly involved.


Treating Preoperative Anemia to Improve Patient Outcomes After Orthopaedic Surgery.
For patients undergoing orthopaedic surgery, preoperative risk modification and control of comorbidities can maximize safety and improve outcomes. Anemia is common among orthopaedic patients, and its prevalence increases with patient age. Although surgeons are well versed in intraoperative blood conservation, preoperative anemia treatment is often deferred to primary care physicians, who may not understand the importance of a thorough assessment and treatment. Orthopaedic surgeons should understand the causes and treatments of anemia to advocate that patients receive appropriate preoperative care. Mean corpuscular volume and reticulocyte count can help determine the cause of anemia and assess the bone marrow's ability to produce red blood cells. These values can be used to aid in diagnosis and treatment plans. Iron deficiency anemia, the most common type, is a microcytic anemia easily treated with iron supplementation. In cases of trauma, anemia can be related to acute blood loss and underlying conditions. Fracture patterns and preexisting comorbidities should be assessed. The role of intravenous iron supplementation in this setting has not been clearly shown. Patients needing urgent procedures that might involve substantial blood loss should receive transfusions if they have hemoglobin levels <8 g/dL or symptomatic anemia.


A bifunctional TPS-TPP enzyme from yeast confers tolerance to multiple and extreme abiotic-stress conditions in transgenic Arabidopsis.
Improving stress tolerance is a major goal for agriculture. Trehalose is a key molecule involved in drought tolerance in anhydrobiotic organisms. Here we describe the construction of a chimeric translational fusion of yeast trehalose-6-phosphate synthase and trehalose-6-phosphate phosphatase. This construct was overexpressed in yeast cells displaying both TPS and TPP enzyme activities and trehalose biosynthesis capacity. In Arabidopsis thaliana, the gene fusion was overexpressed using either the 35S promoter or the stress-regulated rd29A promoter. Transgene insertion in the genome was checked by PCR and transcript expression by RT-PCR. Several independent homozygous lines were selected in the presence of kanamycin and further analyzed. Trehalose was accumulated in all these lines at low levels. No morphological or growth alterations were observed in lines overexpressing the TPS1-TPS2 construct, whereas plants overexpressing the TPS1 alone under the control of the 35S promoter had aberrant growth, color and shape. TPS1-TPS2 overexpressor lines were glucose insensitive, consistent with a suggested role of trehalose/T6P in modulating sugar sensing and carbohydrate metabolism. Moreover, TPS1-TPS2 lines displayed a significant increase in drought, freezing, salt and heat tolerance. This is the first time that trehalose accumulation in plants is shown to protect against freezing and heat stress. Therefore, these results demonstrate that engineering trehalose metabolism with a yeast TPS-TPP bifunctional enzyme confers multiple stress protection in plants, comprising a potential tool to improve stress-tolerance in crops.