Prevalence and characteristics of depressive disorders in early adolescents in central Norway.
Prevalence of depressive disorders among adolescents has varied across studies. The present study aims to assess current and lifetime prevalence and characteristics of adolescent Major Depressive Disorder (MDD), Dysthymia and Depression NOS among adolescents in Central Norway in addition to socio-demographics and use of mental health care. In the Youth and Mental Health Study a representative sample of 2432 junior high school students (mean age 14.9 years, SD = 0.6) from two counties in Central Norway were screened with the Mood and Feelings Questionnaire (MFQ). A subset of 345 of these adolescents (72.5% girls), 220 high scorers (MFQ = > 26), 74 middle scorers (MFQ 7-25), and 50 low scorers (MFQ < 7), 1 unknown score, were drawn and interviewed with the Kiddie SADS-PL (Present-Life Version). In all, 79% had parental interviews as well. All estimates of prevalence rates and population shares were weighted back using a sandwich estimator to yield true population estimates. Almost one in four subjects (23%) had life-time depression. Prevalences of current Major Depressive Disorder (MDD), Dysthymia and "Double depression" were 2.6%, 1.0% and 0.6%, respectively, and for Depression NOS 6.3%.All depressive disorders were characterized by long duration of episodes with large variations, and for any depressive disorder onset before 12 years of age. In multivariate analyses MDD and Dysthymia were most strongly associated with gender and not living with both biological parents. There was no gender difference for Depression NOS. Although a considerable number of depressed subjects had received mental health care, the reason for contact with services was seldom due to affective symptoms. Less than 20% had been in contact with specialist mental health services. High rates of Depression NOS, early onset of depressive episodes, long duration, and low use of specialized services point to the need for improved diagnostic assessment and treatment for young individuals.


IgM, IgG and IgA rheumatoid factors and circulating immune complexes in patients with AIDS and AIDS-related complex with serological abnormalities.
To investigate some humoral aspects which may reflect the involvement of B lymphocytes in the acquired immunodeficiency syndrome (AIDS), we used an enzyme-linked immunoassay (ELISA) to determine the levels of IgM, IgG and IgA rheumatoid factors (RF) in 16 patients suffering from full-blown AIDS and 32 patients with AIDS-related complex (ARC), in the clinical form of lymphoadenopathy syndrome (LAS), compared with 40 healthy, young heterosexual subjects. Both AIDS and ARC patients showed a greater incidence of high IgM RF levels, with mean values significantly higher than controls, but with no differences between the two pathological groups. IgG RF behaviour was similar in the two patient populations and the healthy subjects. IgA RF were significantly raised in AIDS and ARC. Further information on RF was obtained by determination of the immunoglobulin levels of the respective isotypes in the same patients. Mean IgG levels were above normal in AIDS and ARC patients, but the latter group showed a higher incidence of increased values and higher mean levels. The IgA isotype was significantly increased mainly in AIDS patients. The behaviour of IgM was virtually the same in the three groups studied. A difference between AIDS and ARC patients was established by the detection of circulating immune-complexes (IC) by the C1q-binding and CIC-conglutinin assays. IC were significantly high, by both methods, only in the ARC group, but normal or very low in AIDS. These overall findings suggest once again the impairment of B cell function in AIDS, with prevalent hyperactivation in ARC and exhaustion in full-blown AIDS, and apparent preservation, in the latter group, of the antibody responses which are more closely related to the activity of subsets of T helper cells.


Differential Gag-specific polyfunctional T cell maturation patterns in HIV-1 elite controllers.
A small fraction of HIV-infected individuals (<1%), referred to as elite controllers (EC), are able to maintain undetectable viral loads indefinitely without treatment. The role of the maturational phenotype of T cells in the control of HIV infection in these individuals is not well described. We compared the maturational and functional phenotypes of Gag-specific CD4 and CD8 T cells from EC, who maintain undetectable viral loads without treatment; relative controllers (RC), who maintain viral loads of <1,000 copies/ml without treatment; and noncontrollers (NC), who fail to control viral replication. EC maintained higher frequencies of HIV-specific CD4 T cells, less mature polyfunctional Gag-specific CD4 T cells (CD27(+) CD57(-) CD45RO(+)), and Gag-specific polyfunctional CD4 T cells than those observed in NC. In EC, the frequency of polyfunctional Gag-specific CD8 T cells was higher than that observed in RC and NC. RC had a similar functional phenotype to that observed in NC, despite consistently lower viral loads. Finally, we found a direct correlation between the frequency of Gag-specific CD27(+) CD57(-) CD45RO(+) CD4(+) T cells and the frequency of mature HIV-specific CD8 T cells. Altogether, our data suggest that immature Gag-specific interleukin-2 (IL-2)-producing CD4(+) T cells may play an important role in spontaneous control of HIV viremia by effectively supporting HIV-specific CD8 T lymphocytes. This difference appears to differentiate EC from RC.


AZD6280, a novel partial γ-aminobutyric acid A receptor modulator, demonstrates a pharmacodynamically selective effect profile in healthy male volunteers.
AZD6280 is a novel γ-aminobutyric acid A receptor modulator with higher in vitro efficacy at the α2,3 subtypes as compared to the α1 and α5 subtypes. This study compared the pharmacodynamic effects of single oral dose AZD6280 10 mg and 40 mg on the central nervous system with 2 mg of lorazepam. Sixteen healthy males were enrolled into the double-blind, randomized, 4-way crossover study. Two validated central nervous system test batteries, Neurocart and CogState, were administered to measure drug effects on cognition, neurophysiologic function, and psychomotor and subjective feelings. Statistical analysis was performed using mixed model analysis of variance, with fixed factors of treatment, period, time and treatment by time, and random factors of subject, subject by treatment and subject by time, and the average prevalue as covariate. Most pharmacodynamic parameters were affected by lorazepam. AZD6280 induced dose-dependent smaller-than-lorazepam effects on saccadic peak velocity (SPV) (AZD6280, 10 mg vs. AZD6280, 40 mg vs. lorazepam [deg/s]: -22.6 vs. -50.0 vs. -62.9, P < 0.001), whereas the impacts on adaptive-tracking, body-sway, smooth-pursuit, and the one-card-learning tests were significant but much smaller than lorazepam. Thus, the slopes of regression lines for the ΔLog(Sway)-ΔSPV, ΔTracking-ΔSPV, and ΔSmooth-ΔSPV relations were flatter with AZD6280 than with lorazepam. AZD6280 caused a distinct electroencephalography signature from that of lorazepam. The SPV responses to AZD6280 suggest potential concentration-related anxiolytic effects, whereas the smaller SPV-normalized effects of AZD6280 on various non-SPV pharmacodynamic parameters suggest a more favorable side effect profile compared to lorazepam. Overall, the pharmacodynamic profile of AZD6280 matches the pharmacological specificity and selectivity of this compound at the α2,3 γ-aminobutyric acid A receptor subtypes.


Dynamic nuclear envelope phenotype in rats overexpressing mutated human torsinA protein.
A three-base-pair deletion in the human TOR1A gene is causative for the most common form of primary dystonia: the early-onset dystonia type 1 (DYT1 dystonia). The pathophysiological consequences of this mutation are still unknown. To study the pathology of the mutant torsinA (TOR1A) protein, we have generated a transgenic rat line that overexpresses the human mutant protein under the control of the human TOR1A promoter. This new animal model was phenotyped with several approaches, including behavioral tests and neuropathological analyses. Motor phenotype, cellular and ultrastructural key features of torsinA pathology were found in this new transgenic rat line, supporting that it can be used as a model system for investigating the disease's development. Analyses of mutant TOR1A protein expression in various brain regions also showed a dynamic expression pattern and a reversible nuclear envelope pathology. These findings suggest the differential vulnerabilities of distinct neuronal subpopulations. Furthermore, the reversibility of the nuclear envelope pathology might be a therapeutic target to treat the disease.


Dietary Supplementation with Allspice Pimenta dioica Reduces the Occurrence of Streptococcal Disease during First Feeding of Mozambique Tilapia Fry.
Abstract Allspice Pimenta dioica as a feed additive was studied for its effects on growth performance and disease resistance in Mozambique Tilapia Oreochromis mossambicus. Five isonitrogenous (36% crude protein) and isocaloric (18.5 kJ/g) diets were formulated to contain 0 (control), 5, 10, 15, or 20 g of allspice/kg of fish feed. In a 50-d feeding trial, 15 plastic tanks (21 L) were stocked with 35 fish fry (0.012 g) each. After the feeding trial, fish were exposed to Streptococcus iniae and mortalities were recorded. The second-order polynomial regression indicated that the dietary allspice level of 10 g/kg provided the best growth performance and feed utilization. The greatest survival after pathogen challenge was also obtained from the diet supplemented with allspice at 10 g/kg. Therefore, allspice acts as a growth promoter to improve feed utilization and weight gain in Mozambique Tilapia fry and acts an antimicrobial agent to enhance disease resistance during first feeding of fry. These results suggest that allspice can be used as an alternative to antibiotics in controlling streptococcal disease in tilapia culture. Received October 19, 2012; accepted January 20, 2014.


Relationship between herpes simplex virus-1-specific antibody titers and cortical brain damage in Alzheimer's disease and amnestic mild cognitive impairment.
Alzheimer's disease (AD) is a multifactorial disease with a still barely understood etiology. Herpes simplex virus 1 (HSV-1) has long been suspected to play a role in the pathogenesis of AD because of its neurotropism, high rate of infection in the general population, and life-long persistence in neuronal cells, particularly in the same brain regions that are usually altered in AD. The goal of this study was to evaluate HSV-1-specific humoral immune responses in patients with a diagnosis of either AD or amnestic mild cognitive impairment (aMCI), and to verify the possible relation between HSV-1-specific antibody (Ab) titers and cortical damage; results were compared to those obtained in a group of healthy controls (HC). HSV-1 serum IgG titers were measured in 225 subjects (83 AD, 68 aMCI, and 74 HC). HSV-specific Ab avidity and cortical gray matter volumes analyzed by magnetic resonance imaging (MRI) were evaluated as well in a subgroup of these individuals (44 AD, 23 aMCI, and 26 HC). Results showed that, whereas HSV-1 seroprevalence and IgG avidity were comparable in the three groups, increased Ab titers (p < 0.001) were detected in AD and aMCI compared to HC. Positive significant correlations were detected in AD patients alone between HSV-1 IgG titers and cortical volumes in orbitofrontal (region of interest, ROI1 RSp0.56; p = 0.0001) and bilateral temporal cortices (ROI2 RSp0.57; p < 0.0001; ROI3 RSp0.48; p = 0.001); no correlations could be detected between IgG avidity and MRI parameters. Results herein suggest that a strong HSV-1-specific humoral response could be protective toward AD-associated cortical damage.


Thromboxane plays a role in postprandial jejunal oxygen uptake and capillary exchange.
The effects of a thromboxane A2 (TxA2)-endoperoxide receptor antagonist, SQ 29548, on jejunal blood flow, oxygen uptake, and capillary filtration coefficient (Kfc) were determined in anesthetized dogs under resting conditions and during the presence of predigested food in the jejunal lumen in three series of experiments. In series 1, 2.0 micrograms intra-arterial administration of SQ 29548 was found to abolish completely the vasoconstrictor action of graded doses (0.05-2.0 micrograms) of intra-arterial injection of a TxA2-endoperoxide analogue, U44069. SQ 29548 (2.0 micrograms ia) per se did not significantly alter resting jejunal blood flow, oxygen uptake, capillary pressure, or Kfc. Before SQ 29548, placement of food plus bile into the jejunal lumen increased blood flow +42 +/- 9%, oxygen uptake +28 +/- 7%, and Kfc +24 +/- 6%. After SQ 29548, the food placement increased blood flow +37 +/- 8%, oxygen uptake +52 +/- 11%, and Kfc +63 +/- 20%. The food-induced increases in oxygen uptake and Kfc after SQ 29548 were significantly greater than those induced before the blocking of TxA2-endoperoxide receptors by SQ 29548. Our study indicates that endogenous thromboxane does not play a role in regulating jejunal blood flow, capillary filtration, and oxygen uptake under resting conditions. However, it plays a role in limiting the food-induced increases in jejunal oxygen uptake and capillary exchange capacity without influencing the food-induced hyperemia.


MRI assessment of myelination of motor and sensory pathways in the brain of preterm and term-born infants.
A study was performed in 48 neurologically normal preterm and term-born infants, with a postconceptional age at MRI varying between 30 2/7 and 46 weeks and a mean age of 34 2/7 weeks. The purpose of the study was to determine the normal progress of myelination on MRI in that age range. T1- and T2-weighted images of the brain were assessed for changes in signal intensity of white matter relative to gray matter. Multiple sites in the brainstem, cerebellum and cerebral hemispheres were assessed separately. The findings were correlated with the ages of the infants. As judged from relative signal intensities, myelin was present at the post-conceptional age of 30-34 weeks in the following structures: tegmentum pontis (in particular medial lemniscus), superior and inferior colliculi, decussation of the superior cerebellar peduncles, crura cerebri, ventrolateral thalamus, lateral globus pallidus, dorsolateral putamen, dentate nucleus, middle and superior cerebellar peduncles, vermis cerebelli, cortex bordering the central sulcus and hippocampus. Little progress in myelination was noticed up to the post-conceptional age of 46 weeks. Between 34 and 46 weeks, myelin appeared in the lateral part of the posterior limb of the internal capsule and in the central part of the corona radiata and became more prominently visible in the cortex bordering the central sulcus.


Advanced nitrogen elimination by encapsulated nitrifiers.
By introducing a mixed population of nitrifiers encapsulated in gel lens beads a more selective nitrification process was found in treatment of settled sewage in lab scale at a hydraulic retention time (HRT) of about 30 to 60 minutes. The reaction rates for oxidation of soluble chemical oxygen demand (SCOD) were found to vary between 25 to 150 mg/L x h while nitrification takes place around 50 mg nitrogen per hour and litre reaction volume. However, based on this SCOD removal in the nitrification step, a consequent post-denitrification process without nitrate recycle and dosage of external carbon sources has been proven to reach substantial nitrate elimination of up to 20 mg nitrogen per litre at COD/N-ratios of approx. 6 in settled sewage. At such COD/N-ratios, suitable nitrogen elimination seems to be possible, because the bioflocs of settled sewage, produced so far by SCOD oxidation and entrapment of particulate COD, are passing through the nitrification process having a substantial contribution to the denitrification rate additionally to the remaining SCOD.


Inactivation of the calcium-transport ATPase in the sarcoplasmic reticulum by the combined effect of lasolocid and Triton X-100.
The calcium-transport ATPase of the sarcoplasmic reticulum membranes is irreversibly inactivated by the combined action of Lasolocid and Triton X-100 at concentrations which separately do not interfere with the enzyme's activity. In the presence of Lasolocid the enzyme is most susceptible to inactivation when the Triton X-100 concentration just exceeds its critical micellar concentration, approximately, 0.2 mg X ml-1. Lasolocid becomes effective at a concentration of 10 microM and produces rapid inactivation at 100 microM. Phosphoprotein formation is less affected than phosphate liberation. The influence of the ATPase protein on the fluorescence intensity of Lasolocid passes a distinct maximum at the most effective Triton X-100 concentration of 0.2 mg X ml-1.


Resveratrol Downregulates Biomarkers of Sepsis Via Inhibition of Proteasome's Proteases.
Lipopolysaccharide (LPS) is the main agonist of gram-negative bacteria and initiates inflammation. We recently reported that plasmas from sepsis patients revealed increased levels of following group of biomarkers; VCAM-1, ICAM1, CRP, resistin, and proteasome LMP subunits. Our objective here was to compare effects of resveratrol (shown to be a nonspecific proteasome inhibitor by us) and a known LMP7 inhibitor (ONX-0914, specific inhibitor) on proteasome's activities, as well as on inflammatory markers mentioned above in human blood monocytes. Using fluorescence-based assays on blood monocytes purified proteasomes, resveratrol (0-100 μM) inhibited all three protease activities, predominantly LMP7. Similarly, resveratrol inhibited all three protease activities using cell-based luminescence assay. In contrast, ONX-0914 was more selective and potent for LMP7 activity. Resveratrol and ONX-0914, both significantly inhibited expression of LPS-induced biomarkers mentioned above in CD14 monocytes. Moreover, resveratrol itself, as well as in combination with LPS, accumulated pIκBα in CD14 monocytes. Collectively, our data suggest that resveratrol is a less potent inhibitor of all three; CT-like (predominantly LMP7), T-like and PA protease activities and is less toxic to human monocytes than ONX-0914 (a selector inhibitor of only LMP7) as observed by an autophagy detection kit. Also, resveratrol reduces LPS-induced inflammatory cytokine expression by decreasing the translocation of NF-κB due to an increase in inhibitor pIκBα. Therefore, resveratrol can be used to curb inflammation in diseased states like sepsis and other disorders.


Therapeutic potential of IFN-gamma-modified dendritic cells in acute and chronic experimental allergic encephalomyelitis.
Dendritic cells (DC) are antigen-presenting cells specialized to regulate immune responses. DC not only control immunity, but also maintain tolerance to self-antigens-two complementary functions that would ensure the integrity of the organism in an environment full of pathogens. Here we report that splenic DC that had been exposed in vitro to IFN-gamma (IFN-gamma-DC) exhibit therapeutic potential on acute experimental allergic encephalomyelitis (EAE) in Lewis rats, and on chronic-relapsing EAE in B6 and SJL/J mice. During incipient EAE [day 5 post-immunization (p.i.) in rats, day 7 p.i. in mice], IFN-gamma-DC were injected s.c. Severity of clinical signs of EAE was dramatically inhibited in animals injected with IFN-gamma-DC, showing normal magnetic resonance imaging (MRI) of the spinal cord and brain. In contrast, the EAE rats receiving PBS or naive DC had severe clinical signs with multiple and extensive MRI lesions in the spinal cord and brain. IFN-gamma-DC triggered an antigen-specific IFN-gamma production, and induced apoptosis of CD4(+) T cells possibly through DC expressing indoleamine 2,3-dioxygenase and/or an IFN-gamma-dependent pathway. As a result, infiltration of macrophages and CD4(+) T cells within the spinal cords was dramatically reduced in animals injected with IFN-gamma-DC as compared to animals injected with PBS or naive DC. This approach may represent a novel possibility of individualized immunotherapy using autologous, in vitro modified DC as a complement to conventional therapy in multiple sclerosis and other diseases with an autoimmune background.


Integrative study of hypothalamus-pituitary-thyroid-immune system interaction: thyroid hormone-mediated modulation of lymphocyte activity through the protein kinase C signaling pathway.
Thyroid hormones play critical roles in differentiation, growth and metabolism, but their participation in immune system regulation has not been completely elucidated. Modulation of in vivo thyroid status was used to carry out an integrative analysis of the role of the hypothalamus-pituitary-thyroid (HPT) axis in T and B lymphocyte activity. The participation of the protein kinase C (PKC) signaling pathway and the release of some cytokines upon antigenic stimulation were analyzed. Lymphocytes from hyperthyroid mice displayed higher T-and B-cell mitogen-induced proliferation, and those from hypothyroid mice displayed lower T- and B-cell mitogen-induced proliferation, compared with euthyroid animals. Reversion of hypothyroid state by triiodothyronine (T3) administration recovered the proliferative responses. No differences were found in lymphoid subset balance. Both total PKC content and mitogen-induced PKC translocation were higher in T and B cells from hyperthyroid mice, and lower in cells from hypothyroid mice, compared with controls. Levels of thyroid-stimulating (TSH) and TSH-releasing (TRH) hormones were not directly related to lymphocyte proliferative responses. After immunization with sheep red blood cells (SRBCs) and re-stimulation, in vitro spleen cells from hyper- or hypothyroid mice showed, respectively, increased or decreased production of interleukin (IL)-2 and interferon (IFN)-gamma cytokines. Additionally, an increase in IL-6 and IFN-gamma levels was found in hyperthyroid cells after in vivo injection and in vitro re-stimulation with lipopolysaccharide (LPS). Our results show for the first time a thyroid hormone-mediated regulation of PKC content and of cytokine production in lymphocytes; this regulation could be involved in the altered responsiveness to mitogen-induced proliferation of T and B cells. The results also confirm the important role that these hormones play in regulating lymphocyte reactivity.


[Dynamic method of trauma prophylaxis during mass sport exercises].
This article is dedicated to the original technique of prophylactics of sport injuries during mass sport exercises, especially in time of overcoming physical obstacle exercises. The results of the study showed that preliminary application of specially designed training program aimed at improving movement coordination, strengthening responsible muscle groups which are responsible quality of exercises to be completed allows decreasing the level of sport injuries during mass sport exercises among young sportpeople, especially in time of overcoming different physical obstacle exercises.


[Promotion in mental health, nursing creating and intervening with children's stories].
This paper refers to the importance of the childish stories as an instrument for the nursing action and the mental health promotion in childhood. The objective was to veriyj the recognition of the children's emotions, through stories specific to health. This is a descriptive-exploratory study of a qualitative nature, conducted in seven groups meetings with six children aged seven to ten years in an outpatient childish mental health. In the data collection the following were used as instruments: six fairy tales, the play of emotions, emotional faces, drawings, paintings and clay sculptures. Thematic analysis was used in which the following emerged, the recognition of emotions. The children recognized four basics emotions: sadness, joy, fear and anger. It was found in the study that the creation of contextualized stories and the strategy of storytelling group may be useful as a tool for research and qualification of nursing actions, to promote children's mental health.


Piper aduncum against Haemonchus contortus isolates: cross resistance and the research of natural bioactive compounds.
The anthelminthic activity of the essential oil (EO) of Piper aduncum L. was tested in vitro on eggs and larvae of resistant (Embrapa2010) and susceptible (McMaster) isolates of Haemonchus contortus. The EO was obtained by steam distillation and its components identified by chromatography. EO concentrations of 12.5 to 0.02 mg/mL were used in the egg hatch test (EHT) and concentrations of 3.12 to 0.01 mg/mL in the larval development test (LDT). Inhibition concentrations (IC) were determined by the SAS Probit procedure, and significant differences assessed by ANOVA followed by Tukey's test. In the EHT, the IC50 for the susceptible isolate was 5.72 mg/mL. In the LDT, the IC50 and IC90 were, respectively, 0.10 mg/mL and 0.34 mg/mL for the susceptible isolate, and 0.22 mg/mL and 0.51 mg/mL for the resistant isolate. The EO (dillapiole 76.2%) was highly efficacious on phase L1. Due to the higher ICs obtained for the resistant isolate, it was raised the hypothesis that dillapiole may have a mechanism of action that resembles those of other anthelmintic compounds. We further review and discuss studies, especially those conducted in Brazil, that quantified the major constituents of P. aduncum-derived EO.


The effect of competition on the control of invading plant pathogens.
New invading pathogen strains must compete with endemic pathogen strains to emerge and spread. As disease control measures are often non-specific, that is, they do not distinguish between strains, applying control not only affects the invading pathogen strain but the endemic as well. We hypothesize that the control of the invasive strain could be compromised due to the non-specific nature of the control.A spatially explicit model, describing the East African cassava mosaic virus-Uganda strain (EACMV-UG) outbreak, is used to evaluate methods of controlling both disease incidence and spread of invading pathogen strains in pathosystems with and without an endemic pathogen strain present.We find that while many newly introduced or intensified control measures (such as resistant cultivars or roguing) decrease the expected incidence, they have the unintended consequence of increasing, or at least not reducing, the speed with which the invasive pathogen spreads geographically. We identify the controls that cause this effect and methods in which these controls may be applied to prevent it.We found that the spatial spread of the invading strain is chiefly governed by the incidence at the wave front. Control can therefore be applied, or intensified, once the wave front has passed without increasing the pathogen's rate of spread.When trade of planting material occurs, it is possible that the planting material is already infected. The only forms of control in this study that reduces the speed of geographic spread, regardless of the presence of an endemic strain, are those that reduce the amount of trade and the distance over which trade takes place. Synthesis and applications. The best control strategy depends on the presence of competing endemic strains. Applying or intensifying the control can slow the rate of spread when absent but increase it if present. Imposing trade restrictions before the epidemic has reached a given area and intensifying other control methods only when the wave front has passed is the most effective way of both slowing down spread and controlling incidence when a competing endemic strain is present and is the safest approach when its presence is unknown.


The use of method detection limits in environmental measurements.
Environmental measurements often produce values below the method detection limit (MDL). Because low or zero values may be used in determining compliance with regulatory limits, in determining emission factors (typical concentrations emitted by a given type of source), or in modeling efforts, there is considerable interest in methods for determining detection limits and in procedures for using MDLs in summary statistics. Selection of methods for determining detection limits and treatment of MDL data should depend on the end-use of the data. The MDL should be determined in the environmental matrix that contains the analyte of interest. Treatment of missing values (values below the MDL) should be specified before the initiation of a measurement effort. When calculating a mean value for a source or area, one approach is to set the missing values at the MDL. This approach is appropriate when there are significant risks associated with incorrectly assuming a low level of a toxic compound; this method of summarizing data introduces a positive bias. Missing values may be assumed to equal zero if there is not a high risk of overlooking a hazard; this method produces a negative bias. However, if enough measurement data are available and the distribution of these data can be established then look-up tables can be used to estimate missing values, using statistically based estimates, without introducing high or low biases in a calculated mean.


Cortical plasticity in phantom limb pain: A fMRI study on the neural correlates of behavioral clinical manifestations.
The neural mechanism of phantom limb pain (PLP) is related to the intense brain reorganization process implicating plasticity after deafferentation mostly in sensorimotor system. There is a limited understanding of the association between the sensorimotor system and PLP. We used a novel task-based functional magnetic resonance imaging (fMRI) approach to (1) assess neural activation within a-priori selected regions-of-interested (motor cortex [M1], somatosensory cortex [S1], and visual cortex [V1]), (2) quantify the cortical representation shift in the affected M1, and (3) correlate these changes with baseline clinical characteristics. In a sample of 18 participants, we found a significantly increased activity in M1 and S1 as well as a shift in motor cortex representation that was not related to PLP intensity. In an exploratory analyses (not corrected for multiple comparisons), they were directly correlated with time since amputation; and there was an association between increased activity in M1 with a lack of itching sensation and V1 activation was negatively correlated with PLP. Longer periods of amputation lead to compensatory changes in sensory-motor areas; and itching seems to be a protective marker for less signal changes. We confirmed that PLP intensity is not associated with signal changes in M1 and S1 but in V1.


Observational evidence for an ocean heat pump induced by tropical cyclones.
Ocean mixing affects global climate and the marine biosphere because it is linked to the ocean's ability to store and transport heat and nutrients. Observations have constrained the magnitude of upper ocean mixing associated with certain processes, but mixing rates measured directly are significantly lower than those inferred from budget analyses, suggesting that other processes may play an important role. The winds associated with tropical cyclones are known to lead to localized mixing of the upper ocean, but the hypothesis that tropical cyclones are important mixing agents at the global scale has not been tested. Here we calculate the effect of tropical cyclones on surface ocean temperatures by comparing surface temperatures before and after storm passage, and use these results to calculate the vertical mixing induced by tropical cyclone activity. Our results indicate that tropical cyclones are responsible for significant cooling and vertical mixing of the surface ocean in tropical regions. Assuming that all the heat that is mixed downwards is balanced by heat transport towards the poles, we calculate that approximately 15 per cent of peak ocean heat transport may be associated with the vertical mixing induced by tropical cyclones. Furthermore, our analyses show that the magnitude of this mixing is strongly related to sea surface temperature, indicating that future changes in tropical sea surface temperatures may have significant effects on ocean circulation and ocean heat transport that are not currently accounted for in climate models.


Phylogeny and classification of Paris (Melanthiaceae) inferred from DNA sequence data.
Paris (Melanthiaceae) is a temperate genus of about 24 perennial herbaceous species distributed from Europe to eastern Asia. The delimitation of the genus and its subdivisions are unresolved questions in the taxonomy of Paris. The objective of this study is to test the generic and infrageneric circumscription of Paris with DNA sequence data. Phylogenetic analysis of 21 species of Paris based on nuclear ITS and plastid psbA-trnH and trnL-trnF DNA sequence data, alone and in combination, was employed to assess previous classifications. Paris is monophyletic in all analyses. Neither of the two traditionally recognized subgenera (Paris and Daiswa) are monophyletic. Sections Axiparis, Kinugasa, Paris and Thibeticae are monophyletic in only some of the analyses. Species of sections Dunnianae, Fargesianae and Marmoratae are consistently intercalated among species of section Euthyra in all analyses. Strong discordance between nuclear and plastid lineages is detected. The data support the classification of Paris as a single genus rather than as three genera (Daiswa, Kinugasa and Paris sensu stricto). They provide justification for the transfer of section Axiparis from subgenus Paris to subgenus Daiswa and for the combination of sections Dunnianae, Fargesianae and Marmoratae into section Euthyra. The nuclear-plastid discordance is interpreted as the result of interspecific hybridization among sympatric species.


Quantitative Health Risk Assessment of the Chronic Inhalation of Chemical Compounds in Healthcare and Elderly Care Facilities.
Previous studies have described the chemical pollution in indoor air of healthcare and care facilities. From these studies, the main objective of this work was to conduct a quantitative health risk assessment of the chronic inhalation of chemical compounds by workers in healthcare and elderly care facilities (hospitals, dental and general practitioner offices, pharmacies and nursing homes). The molecules of interest were 36 volatile and 13 semi-volatile organic compounds. Several professional exposure scenarios were developed in these facilities. The likelihood and severity of side effects that could occur were assessed by calculating the hazard quotient for deterministic effects, and the excess lifetime cancer risk for stochastic effects. No hazard quotient was greater than 1. Three compounds had a hazard quotient above 0.1: 2-ethyl-1-hexanol in dental and general practitioner offices, ethylbenzene and acetone in dental offices. Only formaldehyde presented an excess lifetime cancer risk greater than 1 × 10-5 in dental and general practitioner offices (maximum value of 3.8 × 10-5 for general practitioners). The health risk for chronic inhalation of most compounds investigated did not appear to be of concern. Some values tend to approach the acceptability thresholds justifying a reflection on the implementation of corrective actions such as the installation of ventilation systems.


Ozone-induced band bending on metal-oxide surfaces studied under environmental conditions.
Ozone adsorption and decomposition on metal oxides is of wide interest in technology and in atmospheric chemistry. Here, ozone-adsorption-induced band bending is observed on Ti- and Fe-oxide model surfaces under dry and humid conditions. Photoelectron spectroscopic studies indicate the effect of charge transfer to O3, which limits the surface coverage of the precursor to decomposition reactions. This is also consistent with the negative pressure dependence observed in previous studies. These results contribute to our fundamental understanding of ozone adsorption and decomposition mechanisms on metal oxides of environmental and technological relevance.


Development and (pre-) clinical assessment of a novel surgical tool for primary and secondary tracheoesophageal puncture with immediate voice prosthesis insertion, the Provox Vega Puncture Set.
Development and (pre-) clinical assessment were performed of a novel surgical tool for primary and secondary tracheoesophageal puncture (TEP) with immediate voice prosthesis (VP) insertion in laryngectomized patients, the Provox Vega Puncture Set (PVPS). After preclinical assessment in fresh frozen cadavers, a multicenter prospective clinical feasibility study in two stages was performed. Stage-1 included 20 patients, and stage-2 had 27. Based on observations in stage-1, the PVPS was re-designed (decrease in diameter of the dilator from 23.5 to 18 Fr.) and further used in stage-2. Primary outcome measure was immediate VP insertion without requiring additional instruments. Secondary outcome measures for comparison of the new with the traditional TEP procedure were: appreciation, ease of use, time consumption, estimated surgical risks and overall preference. A mini-max two-stage study design was used to establish the required sample size. In stage-1, dilatation forces were considered too high in patients with a fibrotic TE wall. With the final thinner version of the PVPS, VPs were successfully inserted into the TEP in 'one-go' in 24/27 (89%) of TEPs: 20 primary and 7 secondary. Participating surgeons rated appreciation, ease of use, time consumption and estimated surgical risks as better. Related adverse events were few and minor. The new PVPS appeared to be the preferred device by all participating surgeons. This study shows that the novel, disposable PVPS is a useful TEP instrument allowing quick and easy insertion of the VP in the vast majority of cases without requiring additional instruments.


Methods to detect CNVs in the human genome.
The detection of quantitative changes in genomic DNA, i.e. deletions and duplications or Copy Number Variants (CNVs), has recently gained considerable interest. First, detailed analysis of the human genome showed a surprising amount of CNVs, involving thousands of genes. Second, it was realised that the detection of CNVs as a cause of genetic disease was often neglected, but should be an essential part of a complete screening strategy. In both cases new efficient CNV screening methods, covering the entire range from specific loci to genome-wide, were behind these developments. This paper will briefly review the methods that are available to detect CNVs, discuss their strong and weak points, show some new developments and look ahead. Methods covered include microscopy, fluorescence in situ hybridization (including fiber-FISH), Southern blotting, PCR-based methods (including MLPA), array technology and massive parallel sequencing. In addition, we will show some new developments, including a 1400-plex CNV bead assay, fast-MLPA (from DNA to result in approximately 6 h) and a simple Melting Curve Analysis assay to confirm potential CNVs. Using the 1400-plex CNV bead assay, targeting selected chromosomal regions only, we detected confirmed rearrangements in 9% of 320 mental retardation patients studied.


The Effect of ASIC3 Knockout on Corticostriatal Circuit and Mouse Self-grooming Behavior.
Stereotypic and/or repetitive behavior is one of the major symptoms of autism spectrum disorder (ASD). Increase of self-grooming behavior is a behavioral phenotype commonly observed in the mouse models for ASD. Previously, we have shown that knockout of acid-sensing ion channel 3 (ASIC3) led to the increased self-grooming behavior in resident-intruder test. Given the facts that ASIC3 is mainly expressed in the peripheral dorsal root ganglion (DRG) and conditional knockout of ASIC3 in the proprioceptors induced proprioception deficits. We speculate a hypothesis that stereotypic phenotype related to ASD, pararalled with striatal dysfunction, might be caused by proprioception defect in the peripheral sensory neuron origin. Herein, we investigate in depth whether and how ASIC3 is involved in the regulation of self-grooming behavior. First, we observed that Asic3 null mutant mice exhibited increased self-grooming in social interaction during juvenile stage. Similarly, they displayed increased self-grooming behavior in a novel cage in the absence of cagemate. To further understand the mechanism by which ASIC3 affects grooming behavior, we analyzed neurochemical, neuropathological and electrophysiological features in the dorsal striatum of Asic3 null mutant mice. Knockout of Asic3 increased dopamine (DA) activity and phospho-ERK immunoreactivities in the dorsal striatum. Furthermore, we detected a lower paired-pulse ratio (PPR) and impaired long-term potentiation (LTP) in corticostriatal circuits in Asic3 null mutant mice as compared with wild-type (WT) littermates. Moreover, knockout of Asic3 altered the medial spiny neurons in the striatum with defects in presynaptic function and decrease of dendritic spines. Lastly, genetic ablation of Asic3 specifically in parvalbumin-positive (PV+) cells resulted in the increase of self-grooming behavior in mice. These findings suggest knockout of Asic3 in the PV+ neurons alters grooming behavior by co-opting corticostriatal circuits.


A case of synovial sarcoma with bone metastasis identified by bone marrow scintigraphy.
In a patient with synovial sarcoma, routine bone survey showed no abnormality, while bone marrow scintigraphy with Tc-99m sulfur colloid revealed a defect in the fifth lumbar vertebra. At surgery, tumorous invasion was noted in the fifth lumbar vertebra and the surrounding tissues. It was suggested that the bone marrow scintigraphy was particularly useful in the detection of tumorous invasion into the bone marrow at the early stage before the destruction of skeletal tissue.


[Magnetic thermotherapy of breast tumors: an experimental therapeutic approach].
The therapeutic strategy for breast cancer is changing, especially for early tumor stages with good prognosis. One potential minimally invasive therapy modality consists in the accumulation of a well-tolerated magnetic material (iron oxides, particularly magnetite) in the target tissue. By applying an alternating magnetic field, energy is selectively absorbed and induces harmful heating of the tumor. The present review deals with the essential conditions and parameters as studied in vitro and in vivo in animal experiments. Extrapolations to the clinical situation are discussed, in particular, the heating potential of the magnetic material, the selection of the magnetic field parameters, the occurrence of eddy currents, the generation of localized heating spots and the expected temperature rises and their effects on the tumor area.


A flow-injection mass spectrometry fingerprinting scaffold for feature selection and quantitation of Cordyceps and Ganoderma extracts in beverage: a predictive artificial neural network modelling strategy.
Flow-injection mass spectrometry (FI/MS) represents a powerful analytical tool for the quality assessment of herbal formula in dietary supplements. In this study, we described a scaffold (proof-of-concept) adapted from spectroscopy to quantify Cordyceps sinensis and Ganoderma lucidum in a popular Cordyceps sinensis /Ganoderma lucidum -enriched health beverage by utilizing flow-injection/mass spectrometry/artificial neural network (FI/MS/ANN) model fingerprinting method with feature selection capability. Equal proportion of 0.1% formic acid and methanol (v/v) were used to convert extracts of Cordyceps sinensis and Ganoderma lucidum into their respective ions under positive MS polarity condition. No chromatographic separation was performed. The principal m/z values of Cordyceps sinensis and Ganoderma lucidum were identified as: 104.2, 116.2, 120.2, 175.2, 236.3, 248.3, 266.3, 366.6 and 498.6; 439.7, 469.7, 511.7, 551.6, 623.6, 637.7 and 653.6, respectively. ANN models representing Cordyceps sinensis and Ganoderma lucidum were individually trained and validated using three independent sets of matrix-free and matrix-matched calibration curves at concentration levels of 2, 20, 50, 100, 200 and 400 μg mL-1. Five repeat analyses provided a total of 180 spectra for herbal extracts of Cordyceps sinensis and Ganoderma lucidum. Root-mean-square-deviation (RMSE) were highly satisfactory at <4% for both training and validation models. Correlation coefficient (r2) values of between 0.9994 and 0.9997 were reported. Matrix blanks comprised of complex mixture of Lingzhi fermentation solution and collagen. Recovery assessment was performed over two days using six sets of matrix blank (n = 6) spiked at three concentration levels of approximately 83, 166 and 333 mg kg-1. Extraction using acetonitrile provided good overall recovery range of 92-118%. A quantitation limit of 0.2 mg L-1 was reported for both Cordyceps sinensis and Ganoderma lucidum. Intra-day and inter-day RMSE values of 7% or better were achieved. Application of the scaffold in a high-throughput routine environment would imply a significant reduction in effort and time, since the option of having a model driven analytical solution is now available.


Fetal monitoring techniques.
It is seen that there are several possible techniques for monitoring the fetus during labor. In addition to those described above, one can take microblood samples from the fetus and analyze for blood gases and pH. The latter is usually the only parameter measured and often is helpful in assessing the fetus. Yet even with spot checks of this chemical determination added to the monitored data, the overall value of fetal monitoring in definitively diagnosing the onset of significant fetal distress must be questioned. Further work and new monitoring techniques and parameters are clearly needed to improve the care of the high risk mother and fetus during labor and delivery.


Engineered nanomaterial-induced lysosomal membrane permeabilization and anti-cathepsin agents.
Engineered nanomaterials (ENMs), or small anthropogenic particles approximately < 100 nm in size and of various shapes and compositions, are increasingly incorporated into commercial products and used for industrial and medical purposes. There is an exposure risk to both the population at large and individuals in the workplace with inhalation exposures to ENMs being a primary concern. Further, there is increasing evidence to suggest that certain ENMs may represent a significant health risk, and many of these ENMs exhibit distinct similarities with other particles and fibers that are known to induce adverse health effects, such as asbestos, silica, and particulate matter (PM). Evidence regarding the importance of lysosomal membrane permeabilization (LMP) and release of cathepsins in ENM toxicity has been accumulating. The aim of this review was to describe our current understanding of the mechanisms leading to ENM-associated pathologies, including LMP and the role of cathepsins with a focus on inflammation. In addition, anti-cathepsin agents, some of which have been tested in clinical trials and may prove useful for ameliorating the harmful effects of ENM exposure, are examined.


Standardization of a cone beam computed tomography machine in evaluating bone density: a novel approach.
Advent of cone beam computed tomography (CBCT) in dentistry has brought us to a new era of precise imaging. Radiographic evaluation of a CBCT image is more informational when compared to CT. The density measurements in CBCT images are based on greyscale values, which are more accurate in CT and these values are inconsistent across various CBCT machines. Hence, we aim at standardizing a single CBCT scanner to evaluate or determine tissue density from the greyscale values. A total of 8 halves of undamaged, dry goat mandibles are included in the study. Scans of the bone are obtained using the KODAK CBCT unit and the PHILLIPS CT machine respectively. Densities are evaluated at 96 points on both the CT scans and the CBCT scans, respectively, using the Radiant Dicom viewer. The obtained data is entered into the excel spreadsheet and subjected to statistical analysis. The greyscale values are obtained from each of the CBCT scans. Hounsfield units are calculated from CT images coinciding with the same points on CBCT scans. The collected data is subjected to linear regression analysis and an equation is derived to determine Hounsfield units (calculated HU units) from greyscale values of CBCT images. We found no significant difference between the mean original HU units and the mean calculated HU units, thus making the equation reliable for calculating HU units from CBCT greyscale values. Our results conclude that the technique was effective in calculating the Original density of tissues using grey standards of CBCT scans.


Hysteroscopic management of menorrhagia.
The hysteroscope has not only the capability of diagnosing abnormal uterine bleeding and managing menorrhagia but also removing space occupying lesions or destruction of the endometrium with electrical or laser treatment. Complications are minimal and success rates are high.


Imaging of Abdominal and Pelvic Manifestations of Graft-Versus-Host Disease After Hematopoietic Stem Cell Transplant.
Graft-versus-host disease (GVHD) is a common complication of hematopoietic stem cell transplant (HSCT). GVHD predominantly affects the skin, gastrointestinal system and hepatobiliary systems. Imaging findings in the gastrointestinal tract include bowel wall thickening with mucosal enhancement, mesenteric edema, and vascular engorgement. In the hepatobiliary system, hepatosplenomegaly, periportal edema, bile duct dilatation, and gallbladder and biliary wall thickening are seen. Although the imaging findings of GVHD are nonspecific, with a known history of HSCT, GVHD should be considered. GVHD is a serious complication of HSCT, which involves multiple organ systems, with imaging manifestations most commonly seen in the gastrointestinal tract and hepatobiliary system. Knowledge of the imaging manifestations of GVHD, which alone may be relatively nonspecific, taken in conjunction with clinical history including the timing and type of HSCT, laboratory values, stool studies, and dermatologic findings can increase radiologist confidence in suggesting this diagnosis.


Visualization and Transport of Positron Emission from Proton Activation in vivo.
Heavy charged particle beams can be widely used for cancer therapy if control in heterogeneous tissue is proved practical. A beam of protons at 200 million electron volts has been visualized in plastic and in a living animal by using an on-line positron camera. The fraction of the activity retained in the radiation site was found to be at least 70 percent of that produced in a dead animal. The sensitivity of the technique was established for a typical geometry.


Agreement between Smoking Self-report and Urine Cotinine among Adolescents.
Cotinine, the major metabolite of nicotine, is a useful marker of exposure to tobacco smoke and self-reporting of smoking status is thought not to be reliable. This study aimed to evaluate the agreement between the smoking self-report among adolescents and the urinary cotinine test. The study subjects were 1226 middle and high school students in Hanam city, who were selected by stratified random sampling. The self-report about smoking behavior was compared with urine cotinine value measured with PBM AccuSignRfi Nicotine (Princeton BioMeditech Corporation, USA). The percentage agreement, kappa and 95% confidence interval (CI) were calculated. The overall percentage agreement was 88.6%, and those for boys, girls, middle school, general school and vocational school students were 87.3%, 90.1%, 93.7%, 85, 5%, 90.7%, and 78.4%, respectively. The overall kappa index was 0.46 (95% CI=0.39-0.54) for overall, and those for boys, girls, middle school, general school and vocational school students were 0.56 (95% CI=0.48-0.65), 0.20 (95% CI=0.07-0.32), 0.21 (95% CI=0.09-0.34), 0.55 (95% CI=0.47-0.64), 0.42 (95% CI=0.33-0.52), and 0.48 (95% CI=0.36-0.60), respectively. The percentage agreement was relatively high but the kappa values very low for girls, and middle school students. Though the prevalence bias can be influenced by these results, the selfreport was not a sufficient tool for the evaluation of adolescents' smoking status, especially in girls or middle school students.


Two nucleotide positions in the Citrus exocortis viroid RNA associated with symptom expression in Etrog citron but not in experimental herbaceous hosts.
Citrus exocortis viroid (CEVd) is the causal agent of exocortis disease of citrus. CEVd has a wide host range that includes woody and herbaceous species. A new CEVd strain (CEVd(COL)), phylogenetically clustering with CEVd variants of Class A inducing severe symptoms in tomato, was identified in Colombia and shown to induce only extremely mild symptoms in Etrog citron indicator plants. Using site-directed mutagenesis, two nucleotide substitutions (314A → G and 315U → A) in the lower strand of the P domain of the predicted CEVd(COL) secondary structure resulted in a severe artificial CEVd(MCOL) variant. Conversely, two nucleotide exchanges (314G → A and 315A → U) in the same region of the severe variant CEVd(E-117) resulted in a symptomless artificial CEVd(ME-117) variant. Infectivity assays conducted with the natural and mutated variants showed that all induced severe symptoms in Gynura aurantiaca, tomato and chrysanthemum. This is the first report of the identification of pathogenic determinants of CEVd in citrus, and shows that these pathogenicity determinants are host dependent.


Mercury speciation in Scottish raptors reveals high proportions of inorganic mercury in Scottish golden eagles (Aquila chrysaetos): Potential occurrence of mercury selenide nanoparticles.
Knowledge of the uptake and fate of mercury (Hg) compounds in biota is important in understanding the global cycling of Hg and its transfer pathways through food chains. In this study, we analysed total mercury (T-Hg) and methylmercury (MeHg) concentrations in 117 livers of Scottish birds of prey that were found across Scotland and submitted for post-mortem examination through the Raptor Health Scotland project between 2009 and 2019. Statistical comparisons focussed on six species (barn owl, Tyto alba; Eurasian common buzzard, Buteo buteo; golden eagle, Aquila chrysaetos; hen harrier, Circus cyaneus; Eurasian sparrowhawk, Accipiter nisus; and tawny owl, Strix aluco) and showed that golden eagles had a statistically lower fraction of MeHg compared to other raptor species. Further investigation using stable carbon and stable nitrogen isotope ratio measurements carried out for the golden eagles (n = 15) indicated that the increased presence of inorganic mercury (iHg) correlated with a marine influence on the primarily terrestrial diet. Additional bioimaging (n = 1) with laser ablation - inductively coupled plasma - mass spectrometry indicated the co-location of Hg and selenium (Se) within the liver tissue and transmission electron microscopy showed evidence of nanoparticles within the range of 10-20 nm. Further analysis using single particle - inductively coupled plasma - mass spectrometry (n = 4) confirmed the presence of Hg nanoparticles. Together, the evidence suggests the presence of mercury selenide (HgSe) nanoparticles in the liver of some golden eagles that, to our knowledge, has never been directly observed in terrestrial birds of prey. This study points to two alternative hypotheses: these golden eagles may be efficient at breaking down MeHg and form HgSe nanoparticles as a detoxification mechanism (as previously observed in cetaceans), or some golden eagles with elevated iHg may have accumulated these nanoparticles by foraging on stranded cetaceans or seabirds.


Remarkable Role of Grain Boundaries in the Thermal Transport Properties of Phosphorene.
In this work, we study the effect of grain boundary (GB) on the thermal transport of phosphorene by using molecular dynamics simulations. By exploring a total of 19 GBs with different GB defect types and densities, we find that there is a relatively high Kapitza thermal boundary resistance at these boundaries. By analyzing the spatial distributions of the heat flux, we find that this high thermal boundary resistance can be attributed to the strong phonon-boundary scattering at the GBs. With the same type of defect, the thermal boundary resistance is found to increase with the increase of the defect density along the GBs, which can be attributed to the nonuniform distribution of stress and lattice distortion. Finally, we investigate the anisotropy in the thermal conductivity of phosphorene with GBs and reveal a strikingly high anisotropy ratio of thermal conductivities, which is found to arise from the different influences of boundaries on the thermal transport along the zigzag and armchair directions. Our results highlight the importance of GBs in the transport behavior of phosphorene and the need to include their effects in the thermal management of phosphorene-based electronic devices.


[The transplantation of hemopoietic cells in patients with solid tumors].
Evaluation of efficiency of bone marrow and peripheral stem cells transplantation in patients with solid tumors. A total of 38 patients aged 30-40 years with stage III or IV solid tumors (15 cases of breast cancer, 5 cases of Ewing's sarcoma, 4 cases of osteogenic sarcoma, ovarian or testicular tumors, 3 cases of soft tissue sarcoma) underwent high-dose polychemotherapy with autologous hematopoietic rescue. All the patients were resistant to the first line chemotherapy or were in relapse of the disease. 21, 11 and 6 patients were transplanted bone marrow, peripheral blood stem cells and both bone marrow and peripheral blood stem cells, respectively. The only factor which influenced overall survival of the patients was the stage of the disease at the moment of the transplantation. 66% of patients in complete or partial remission survived 3 years versus 16.6% of those in progression or relapse of the disease. Other parameters such as the patients' age, the source of hemopoietic cells, number of chemotherapy courses were not essential for the survival. 2 patients died after transplantation. The main cause of death was relapse or progression of the disease after the transplantation. Transplantation of hemopoietic cells is a promising therapy of patients with solid tumors sensitive to chemotherapy.


The Role of the Human Hypothalamus in Food Intake Networks: An MRI Perspective.
Hypothalamus (HT), this small structure often perceived through the prism of neuroimaging as morphologically and functionally homogeneous, plays a key role in the primitive act of feeding. The current paper aims at reviewing the contribution of magnetic resonance imaging (MRI) in the study of the role of the HT in food intake regulation. It focuses on the different MRI techniques that have been used to describe structurally and functionally the Human HT. The latest advances in HT parcellation as well as perspectives in this field are presented. The value of MRI in the study of eating disorders such as anorexia nervosa (AN) and obesity are also highlighted.


Intimate partner violence and early child growth: a community-based cohort study in Nicaragua.
This study analyses whether a mother's exposure to different forms of Intimate Partner Violence (IPV) during pregnancy was associated with the index child linear growth, and whether these associations were modified by the gender of the child. A pregnancy cohort of 478 women in León, Nicaragua, resulted in 461 live births. From this group, 81% (375/461) children were available for anthropometric follow-up at 40 to 46 months. Analysis of covariance (ANCOVA) was used to assess the association between IPV and height-for-age Z-scores, adjusting for confounding factors. Sixty-three percent (236/375) of the mothers had been exposed to some form of IPV during pregnancy (emotional, physical, sexual or controlling behavior). After adjustment for confounding factors, maternal exposure to any IPV during pregnancy was associated with 0.24 lower mean height-for-age Z-scores (p = 0.02). A separate analysis of each IPV type showed that emotional, physical or sexual IPV during pregnancy were not significantly associated with lower mean height-for-age Z-scores, whereas ever exposure to controlling behavior by the father of the child was related to 0.29 lower mean height-for-age Z-scores (p < 0.01) When stratified by gender, these associations remained significant only for young girls. This study has contributed to the growing amount of evidence pointing to the pervasive effect of different forms of IPV on child health. Our study highlights the relevance of maternal autonomy for linear child growth, especially for young girls in the Nicaraguan context.


A brief tool to assess capacity to consent for medical care among homeless individuals with problematic substance use: study protocol.
Public health care increasingly uses outreach models to engage individuals who are marginalized, many of whom misuse substances. Problematic substance use, together with marginalization from the health care system, among homeless adults makes it difficult to assess their capacity to consent to medical care. Tools have been developed to assess capacity to consent; however, these tools are lengthy and unsuitable for outreach settings. The primary objective of this study is to develop, validate, and pilot a brief but sensitive screening instrument which can be used to guide clinicians in assessing capacity to consent in outreach settings. The goal of this paper is to outline the protocol for the development of such a tool. A brief assessment tool will be developed and compared to the MacArthur Competency Assessment Tool for Treatment (MacCAT-T). As list of 36 possible questions will be created by using qualitative data from clinician interviews, as well as concepts from the literature. This list will be rated by content experts according to the extent that it corresponds to the test objectives. The instrument will be validated with 300 homeless adult volunteers who self-report problematic substance use. Participants will be assessed for capacity using the MacCAT-T and the new instrument. A combination of Classical Test Theory and advanced psychometric methods will be used for the psychometric analysis. Corrected Item-Total correlation will be examined to identify items that discriminate poorly. Guided exploratory factor analysis will be conducted on the final selection of items to confirm the assumptions for a unidimensional polytomous Rasch model. If unidimensionality is confirmed, an unstandardized Cronbach Alpha will be calculated. If multi-dimensionality is detected, a multidimensional Rasch analysis will be conducted. Results from the new instrument will be compared to the total score from the MacCAT-T by using Pearson's correlation test. The new instrument will then be piloted in real-time by street outreach clinicians to determine the acceptability and usefulness of the new instrument. This research will build on the existing knowledge about assessing capacity to consent and will contribute new knowledge about assessing individuals whose judgment is impaired by substance use.


Ultrastructural studies of the formation of the egg capsule in the hermaphroditic species, Isohypsibius granulifer granulifer Thulin, 1928 (Eutardigrada: Hypsibiidae).
The egg capsule of Isohypsibius granulifer granulifer Thulin 1928 (Eutardigrada: Hypsibiidae) is composed of two shells: the thin vitelline envelope and the multilayered chorion. The process of the formation of the egg shell begins in middle vitellogenesis. The I. g. granulifer vitelline envelope is of the primary type (secreted by the oocyte), but the chorion should be regarded as a mixed type: primary (secreted by the oocyte), and secondary (produced by the cells of gonad wall). During early choriogenesis, the parts of the chorion are produced and then connected into a permanent layer. The completely developed chorion consists of three layers: (1) the inner, medium electron dense layer; (2) the middle labyrinthine layer; (3) the outer, medium electron dense layer. After the formation of the chorion, a vitelline envelope is secreted by the oocyte.


Purpose in life and cognitive performance and informant ratings of cognitive decline, affect, and activities.
To examine (1) the association between purpose in life and multiple domains of cognitive function and informant-rated cognitive decline, affect, and activities; (2) whether these associations are moderated by sociodemographic factors, cognitive impairment, or depression; (3) whether the associations are independent of other aspects of well-being and depressive symptoms. As part of the 2016 Harmonized Cognitive Assessment Protocol from the Health and Retirement Study, participants completed a battery of cognitive tests and nominated a knowledgeable informant to rate their cognitive decline, affect, and activities. Participants with information available on their purpose in life from the 2014/2016 Leave Behind Questionnaire were included in the analytic sample (N = 2,812). Purpose in life was associated with better performance in every cognitive domain examined (episodic memory, speed-attention, visuospatial skills, language, numeric reasoning; median β =.10, p <.001; median d =.53). Purpose was likewise associated with informant-rated cognitive decline and informant-rated affective and activity profiles beneficial for cognitive health (median β =.18, p < .001; median d =.55). There was little evidence of moderation by sociodemographic or other factors (e.g., depression). Life satisfaction, optimism, positive affect, and mastery were generally associated with cognition. When tested simultaneously with each other and depressive symptoms, most dimensions were reduced to non-significance; purpose remained a significant predictor. Purpose in life is associated with better performance across numerous domains of cognition and with emotional and behavioral patterns beneficial for cognitive health that are observable by knowledgeable others. These associations largely generalize across demographic and clinical groups and are independent of other aspects of well-being.


A novel costimulatory factor for gamma interferon induction found in the livers of mice causes endotoxic shock.
Administration of monoclonal anti-CD3 antibody to mice treated with Propionibacterium acnes induced secretion of a high level of gamma interferon (IFN-gamma) into the circulation system, while it induced no significant release in untreated mice. In order to analyze this high-level induction of IFN-gamma in these bacterium-treated mice, we investigated the factors that might be involved. An activity that induces IFN-gamma in T cells was observed in the liver extracts of mice treated with P. acnes and subsequently challenged with lipopolysaccharide. Here, we purified an IFN-gamma-inducing factor from the liver extract to homogeneity and characterized it. Its molecular mass was 18 to 19 kDa, and its pI was 4.9. The amino acid sequence of the NH2-terminal portion was determined and shown to have no similarities to any protein in the EMBL, GenBank, and PIR data bases. The same molecule was also demonstrated in the serum factor that was previously reported to have an IFN-gamma-inducing activity and to have an apparent molecular mass of 75 kDa. Moreover, the activity of this serum factor was recovered in the fraction containing the 18- to 19-kDa protein under reducing conditions and was shown to have the same NH2-terminal amino acid sequence as that of the factor from the liver extract. In addition to the ability to induce IFN-gamma, this protein augmented T-cell proliferation and NK activity in the spleen cells. Thus, several of its biological activities were apparently similar to those of interleukin-12. These results indicated that this novel protein, which exhibited marked costimulatory activity on IFN-gamma production in vitro, was elevated vivo in response to P. acnes treatment. This factor, probably released from the producing cells by lipopolysaccharide stimuli, may be involved in the high-level induction of IFN-gamma in the P. acnes-treated mice.


Repeated measurement of maternal weight during pregnancy. Is this a useful practice?
A retrospective study of 1092 pregnant women showed that the use of a centile chart of maternal weight gain was not effective at detecting women who give birth to small for gestational age (SGA) infants. Multiple regression analysis showed that of the various weight measurements recorded, weekly weight gain and maternal size at booking were the only factors which had a significant association with infant birthweight after taking into account maternal gestation, age, smoking habit and parity. Low maternal booking weight (less than 51 kg) was the most effective maternal weight measurement for antenatal detection of SGA infants (positive predictive value 20.0%). Low average weekly maternal weight gain (less than 0.20 kg) had a positive predictive value of only 12.9% for detecting these pregnancies. Weight loss or failure to gain weight over a 2-week interval occurring in the third trimester was observed in 46% of all women studied. Maternal smoking had a positive predictive value of 16.3% in antenatal detection of SGA infants. Maternal weight need be recorded only at booking, with the exception of patients in whom nutrition is of concern. The subsequent routine weighing of patients may produce unnecessary anxiety and should cease.


Instantaneous photosynthetically available radiation models for ocean waters using neural networks.
Instantaneous photosynthetically available radiation (IPAR) at the ocean surface and its vertical profile below the surface play a critical role in models to calculate net primary productivity of marine phytoplankton. In this work, we report two IPAR prediction models based on the neural network (NN) approach, one for open ocean and the other for coastal waters. These models are trained, validated, and tested using a large volume of synthetic datasets for open ocean and coastal waters simulated by a radiative transfer model. Our NN models are designed to predict IPAR under a large range of atmospheric and oceanic conditions. The NN models can compute the subsurface IPAR profile very accurately up to the euphotic zone depth. The root mean square errors associated with the diffuse attenuation coefficient of IPAR are less than 0.011m-1 and 0.036m-1 for open ocean and coastal waters, respectively. The performance of the NN models is better than presently available semi-analytical models, with significant superiority in coastal waters.


Purification and characterization of DNA polymerase II from the yeast Saccharomyces cerevisiae. Identification of the catalytic core and a possible holoenzyme form of the enzyme.
We have purified yeast DNA polymerase II to near homogeneity as a 145-kDa polypeptide. During the course of this purification we have detected and purified a novel form of DNA polymerase II that we designate as DNA polymerase II. The most highly purified preparations of DNA polymerase II are composed of polypeptides with molecular masses of 200, 80, 34, 30, and 29 kDa. Immunological analysis and peptide mapping of DNA polymerase II and the 200-kDa subunit of DNA polymerase II indicate that the 145-kDa DNA polymerase II polypeptide is derived from the 200-kDa polypeptide of DNA polymerase II. Activity gel analysis shows that the 145- and the 200-kDa polypeptides have catalytic function. The polypeptides present in the DNA polymerase II preparation copurify with the polymerase activity with a constant relative stoichiometry during chromatography over five columns and co-sediment with the activity during glycerol gradient centrifugation, suggesting that this complex may be a holoenzyme form of DNA polymerase II. Both forms of DNA polymerase II possess a 3'-5' exonuclease activity that remains tightly associated with the polymerase activity during purification. DNA polymerase II is similar to the proliferating cell nuclear antigen (PCNA)-independent form of mammalian DNA polymerase delta in its resistance to butylpheny-dGTP, template specificity, stimulation of polymerase and exonuclease activity by KCl, and high processivity. Although calf thymus PCNA does not stimulate the activity of DNA polymerase II on poly(dA):oligo(dT), possibly due to the limited length of the template, the high processivity of yeast DNA polymerase II on this template can be further increased by the addition of PCNA, suggesting that conditions may exist for interactions between PCNA and yeast DNA polymerase II.


Kinetic analyses of retaining endo-(xylo)glucanases from plant and microbial sources using new chromogenic xylogluco-oligosaccharide aryl glycosides.
A library of phenyl beta-glycosides of xylogluco-oligosaccharides was synthesized via a chemoenzymatic approach to produce new, specific substrates for xyloglucanases. Tamarind xyloglucan was completely hydrolyzed to four, variably galactosylated component oligosaccharides based on Glc 4 backbones, using a Trichoderma endo-glucanase mixture. Oligosaccharide complexity could be further reduced by beta-galactosidase treament. Subsequent per- O-acetylation, alpha-bromination, phase-transfer glycosylation, and Zemplen deprotection yielded phenyl glycosides of XXXG and XLLG oligosaccharides with a broad range of aglycon p K a values. Kinetic and product analysis of the action of the archetypal plant endo-xyloglucanase, Tropaeolum majus NXG1, on these compounds indicated that formation of the glycosyl-enzyme intermediate was rate-limiting in the case of phenol leaving groups with p K a values of >7, leading exclusively to substrate hydrolysis. Conversely, substrates with aglycon p K a values of 5.4 gave rise to a significant amount of transglycosylation products, indicating a change in the relative rates of formation and breakdown of the glycosyl-enzyme intermediate for these faster substrates. Notably, comparison of the initial rates of XXXG-Ar and XLLG-Ar conversion indicated that catalysis by TmNXG1 was essentially insensitive to the presence of galactose in the negative subsites for all leaving groups. More broadly, analysis of a selection of enzymes from CAZy families GH 5, 12, and 16 indicated that the phenyl glycosides are substrates for anomeric configuration-retaining endo-xyloglucanases but are not substrates for strict xyloglucan endo-transglycosylases (XETs). The relative activities of the GH 5, 12, and 16 endo-xyloglucanases toward GGGG-CNP, XXXG-CNP, and XLLG-CNP reflected those observed using analogous high molar mass polysaccharides. These new chromogenic substrates may thus find wide application in the discovery, screening, and detailed kinetic analysis of new xyloglucan-active enzymes.


Neuregulin 1-erbB2 signaling is required for the establishment of radial glia and their transformation into astrocytes in cerebral cortex.
Radial glial cells and astrocytes function to support the construction and maintenance, respectively, of the cerebral cortex. However, the mechanisms that determine how radial glial cells are established, maintained, and transformed into astrocytes in the cerebral cortex are not well understood. Here, we show that neuregulin-1 (NRG-1) exerts a critical role in the establishment of radial glial cells. Radial glial cell generation is significantly impaired in NRG mutants, and this defect can be rescued by exogenous NRG-1. Down-regulation of expression and activity of erbB2, a member of the NRG-1 receptor complex, leads to the transformation of radial glial cells into astrocytes. Reintroduction of erbB2 transforms astrocytes into radial glia. The activated form of the Notch1 receptor, which promotes the radial glial phenotype, activates the erbB2 promoter in radial glial cells. These results suggest that developmental changes in NRG-1-erbB2 interactions modulate the establishment of radial glia and contribute to their appropriate transformation into astrocytes.


Selective modulation of the cyclin B/CDK1 and cyclin D/CDK4 complexes during in vitro human megakaryocyte development.
Mammalian megakaryocyte development is characterized by a progressive accumulation of cells exhibiting a polylobated nucleus with a polyploid DNA content. In this study human megakaryocytes were obtained from CD34+ haemopoietic progenitors by in vitro liquid culture in the presence of 100 ng/ml of recombinant thrombopoietin (TPO). Ultrastructural examination of polyploid megakaryocytes showed the presence of a large number of centrioles, the breakdown of the nuclear envelope, and the progressive chromatin condensation, all aspects characteristic of mitosis. At both indirect immunofluorescence and Western blot analyses, cyclin B and its related cyclin-dependent kinase (CDK)1, which forms the mitosis promoting factor (MPF), showed an increased expression in maturating megakaryoblasts and megakaryocytes (day 8 of culture) with respect to freshly isolated CD34+ progenitors. This expression tended to decline in fully developed megakaryocytes (day 15 of culture). The amount of cyclin D and of the related CDK4, governing the G1 phase of the cell cycle, increased during megakaryocyte development, maintaining high levels of expression also in mature megakaryocytes. These results indicate that megakaryocyte polyploidization depends on a true, although incomplete, mitotic process, and that cyclin D/CDK4 probably plays a crucial role throughout megakaryocytopoiesis.


A scoping review of the feasibility, acceptability, and effects of physiotherapy delivered remotely.
To review the feasibility, acceptability, and effects of physiotherapy when delivered remotely. CINAHL, MEDLINE, EBM Reviews, and Cochrane Library databases (January 2015-February 2022) were searched and screened for papers (of any design) investigating remote physiotherapy. Data were extracted by two independent raters. Methodological quality of the identified papers was not assessed. Thematic content analysis drew out the key issues. Forty-one papers (including nine systemic reviews and six with meta-analyses) were selected involving musculoskeletal, stroke and neurological, pulmonary, and cardiac conditions. The most commonly delivered intervention was remote exercise provision, usually following assessment which was completed in-person. All studies, which assessed it, found that remote physiotherapy was comparably effective to in-person delivery at lower cost. Patient satisfaction was high, they found remote physiotherapy to be more accessible and convenient. It boosted confidence and motivation by reminding patients when and how to exercise but adherence was mixed. No adverse events were reported. Barriers related to access to the technology; technical problems and concerns about therapists' workload. Remote physiotherapy is safe, feasible, and acceptable to patients. Its effects are comparable with traditional care at lower cost.IMPLICATIONS FOR REHABILITATIONRemote physiotherapy is safe, feasible, and acceptable to patients with comparable effects to in-person care.Remote delivery increases access to physiotherapy especially for those who cannot travel to a treatment facility whether due to distance or disability.Remote physiotherapy may increase adherence to exercise by reminding patients when and how to exercise.Remote physiotherapy does not suit everyone, thus a hybrid system with both in-person and remote delivery may be most effective.


Studying the impact of S9 on cyto-genotoxicity of cigarette smoke in human peripheral blood lymphocytes in vitro.
In present study, human lymphocytes were exposed to cigarette smoke condensates (CSCs) at the doses of 25, 50, 75, 100 and 125 μg ml(-1) with and without S9, and the cyto-genotoxic effects were detected with CCK-8, cell apoptosis and micronucleus assays. DNA repair kinetics was observed with comet assay. Our results indicated that the cell viability decreased with CSCs doses, the percentages of apoptosis cell and the frequencies of micronuclei increased with CSCs doses, and DNA damage of human lymphocytes induced by CSCs could be basically repaired within 240 min. However, the cytotoxicity induced by CSCs +S9 was significantly lower than that induced by CSCs -S9 in CCK-8 and cell apoptosis assays, and the DNA repair speed in +S9 group was quicker than that in -S9 group. In conclusion, S9 may affect not only the cyto-genotoxicity of CSCs but also the repair process of DNA damage induced by CSCs in lymphocytes.


Important Elements in the Quality Improvement Curriculum for Orthopaedic Residents.
Orthopaedic residency education requires trainees to participate not only in clinical and research endeavors but also in quality improvement (QI) projects. To our knowledge, little has been published on how to implement a structured QI curriculum as part of an orthopaedic residency program. This article describes a single institution's experience with developing a longitudinal, integrated, and collaborative resident QI curriculum. The Six Sigma DMAIC (Define, Measure, Analyze, Improve, and Control) process was taught to residents as a formal curriculum at our institution beginning in 2014. A structured integrated process was developed for residents to work in teams and meet on a monthly basis. Since then, residents have developed multiple QI projects with measured outcomes. Serial surveys have been administered to the residents to collect feedback. Seven major QI projects have been implemented by residents since the program's initiation. The resident surveys revealed significant improvement in comfort level with organizing QI projects. Residents also reported being comfortable working in interprofessional teams and incorporating patient safety techniques into clinical practice. There are few guidelines that reflect how to initiate a formal QI curriculum in an orthopaedic residency program to promote a standardized and systematic way to approach QI projects. With a structured DMAIC education plan, an emphasis on graded responsibilities within a team setting, and responsiveness to resident feedback, orthopaedic programs can develop an effective QI program to allow residents to learn valuable patient safety practices, which allows residents to have a meaningful and impactful effect on QI initiatives that will serve them well as they enter clinical practice.


Pain Acceptance Decouples the Momentary Associations Between Pain, Pain Interference, and Physical Activity in the Daily Lives of People With Chronic Pain and Spinal Cord Injury.
Pain acceptance is a robust predictor of adjustment to chronic pain; however, the dynamics of pain acceptance in daily life are largely unexamined. Furthermore, research on pain acceptance in those with pain and physical disability is needed. To examine pain acceptance in daily life, we collected 7 days of ecological momentary assessments of pain intensity and pain interference (5 times per day) with continuous accelerometry (physical activity) in 128 individuals with chronic pain and spinal cord injury. Multilevel modeling revealed that pain acceptance significantly moderated the momentary association between pain intensity and pain interference; those with higher pain acceptance experienced a blunted increase in interference when pain was high. Pain acceptance also moderated the association between pain intensity and physical activity; high pain acceptance was associated with an increase and low pain acceptance with a decrease in physical activity in the context of high pain. The activities engagement component of pain acceptance was a slightly more robust driver of these interaction effects; whereas activities engagement significantly moderated the association between momentary pain and pain interference as well as physical activity, pain willingness exerted a significant moderating effect on the momentary association between pain intensity and pain interference only. These findings suggest that both components contribute to the decoupling effects of pain acceptance. Task persistence did not show the same moderating effects, indicating that pain acceptance may be unique from other types of behavioral pain coping in its ability to decouple expected associations between pain intensity, pain interference, and physical activity. In the daily lives of individuals with chronic pain and spinal cord injury, pain acceptance buffered expected increases in pain interference and decreases in physical activity in the context of high pain. These findings can inform further development of models of chronic pain adjustment and of more efficient, effective treatment approaches.


[Complex analysis of risk factors of hypertension in subjects involved in managerial activity].
We performed complex analysis of genetic and nongenetic factors facilitating development of arterial hypertension in subjects involved in managerial activity and revealed peculiarities of dermatoglyphic phenotype of susceptibility to this type of pathology. By means of methods of pattern recognition we assessed power and character of effect of each of investigated risk factors. Using mathematical model we elaborated prognosis of efficacy of various preventive procedures. Basing on results of this study we created system of criteria for formation of a group of elevated risk of hypertension and system of measures aimed at prevention of cardiovascular diseases in subjects involved in neuro-emotional labor.


Effects of using different roughages in the total mixed ration inoculated with or without coculture of Lactobacillus acidophilus and Bacillus subtilis on in vitro rumen fermentation and microbial population.
This study aimed to determine the effects of different roughages in total mixed ration (TMR) inoculated with or without coculture of Lactobacillus acidophilus (L. acidophilus) and Bacillus subtilis (B. subtilis) on in vitro rumen fermentation and microbial population. Three TMRs formulations composed of different forages were used and each TMR was grouped into two treatments: non-fermented TMR and fermented TMR (F-TMR) (inoculated with coculture of L. acidophilus and B. subtilis). After fermentation, the fermentation, chemical and microbial profile of the TMRs were determined. The treatments were used for in vitro rumen fermentation to determine total gas production, pH, ammonianitrogen (NH3-N), and volatile fatty acids (VFA). Microbial populations were determined by quantitative real-time polymerase chain reaction (PCR). All data were analyzed as a 3×2 factorial arrangement design using the MIXED procedure of Statistical Analysis Systems. Changes in the fermentation (pH, lactate, acetate, propionate, and NH3-N) and chemical composition (moisture, crude protein, crude fiber, and ash) were observed. For in vitro rumen fermentation, lower rumen pH, higher acetate, propionate, and total VFA content were observed in the F-TMR group after 24 h incubation (p<0.05). F-TMR group had higher acetate concentration compared with the non-fermented group. Total VFA was highest (p<0.05) in F-TMR containing combined forage of domestic and imported source (F-CF) and F-TMR containing Italian ryegrass silage and corn silage (F-IRS-CS) than that of TMR diet containing oat, timothy, and alfalfa hay. The microbial population was not affected by the different TMR diets. The use of Italian ryegrass silage and corn silage, as well as the inoculation of coculture of L. acidophilus and B. subtilis, in the TMR caused changes in the pH, lactate and acetate concentrations, and chemical composition of experimental diets. In addition, F-TMR composed with Italian ryegrass silage and corn silage altered ruminal pH and VFA concentrations during in vitro rumen fermentation experiment.


[Activity of aldehyde scavenger enzymes in the heart of rats of different age during immobilized stress].
This study was made to determine the activity of aldehyde scavenger enzymes in the heart's postmitochondrial fraction of rats of different age during immobilization stress. Our study demonstrated, that immobilization of 1.5-, 2- and 12-month rats was accompanied by inhibiting activity of aldehyde dehydrogenase and aldehyde reductase. At the same time we observed an increase in glutathione transferase activity in immobilized 1.5-month-old rats and that in reductase activity in 24-month-old rats. The revealed changes can lead to a decrease in the rate of endogenous aldehyde utilization in the heart during stress at puberty.


Assessment of feasibility to use computer aided texture analysis based tool for parametric images of suspicious lesions in DCE-MR mammography.
Our aim was to analyze the feasibility of computer aided malignant tumor detection using the traditional texture analysis applied on two-compartment-based parameter pseudoimages of dynamic contrast-enhanced magnetic resonance (DCE-MR) breast image data. A major contribution of this research will be the through-plane assessment capability. Texture analysis was performed on two-compartment-based pseudo images of DCE-MRI datasets of breast data of eight subjects. The resulting texture parameter pseudo images were inputted to a feedforward neural network classification system which uses the manual segmentations of a primary radiologist as a gold standard, and each voxel was assigned as malignant or nonmalignant. The classification results were compared with the lesions manually segmented by a second radiologist. Results show that the mean true positive fraction (TPF) and false positive fraction (FPF) performance of the classifier vs. primary radiologist is statistically as good as the mean TPF and FPF performance of the second radiologist vs. primary radiologist with a confidence interval of 95% using a one-sample t-test with α = 0.05. In the experiment implemented on all of the eight subjects, all malignant tumors marked by the primary radiologist were classified to be malignant by the computer classifier. Our results have shown that neural network classification using the textural parameters for automated screening of two-compartment-based parameter pseudo images of DCE-MRI as input data can be a supportive tool for the radiologists in the preassessment stage to show the possible cancerous regions and in the postassessment stage to review the segmentations especially in analyzing complex DCE-MRI cases.


Non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation in secondary stroke and systemic embolism prevention.
Oral anticoagulants (OAC) are recommended in all patients with atrial fibrillation (AF) after thromboembolic events without contraindications. It is hypothesized herein, that the majority of patients with AF after thromboembolic events receive OAC and the presence of specific factors, predisposes the use of non-vitamin K antagonist oral anticoagulants (NOACs). This is a retrospective study, encompassing patients with AF hospitalized in a reference cardiology center over the years 2014-2017. Thromboembolic events were defined as: ischemic stroke, transient ischemic attack and systemic embolism. Inclusion criteria were the following: diagnosis of non-valvular AF at discharge from hospital, hospitalization not resulting in death. Among 2834 hospitalized patients with AF, a history of thromboembolic events was identified in 347 (12.2%) patients. In the group studied, of 347 patients with AF after a thromboembolic event, 322 (92.8%) received OAC, including 133 patients on vitamin K antagonist (41.3% of patients on OAC) and 189 patients on NOACs (58.7% of patients on OAC). Among patients treated with NOACs the majority were on dabigatran (116 patients, 61.4%), followed by rivaroxaban (54 patients, 28.6%), and apixaban (19 patients, 10%). Multivariate logistic regression analysis demonstrated that the presence of arterial hypertension reduced the chance for NOACs use (odds ratio [OR] 0.4, 95% confidence interval [CI] 0.2-0.9, p = 0.04) and left atrial size ≤ 40 mm was a factor increasing the chance for the use of NOACs (OR 2.5, 95% CI 1.1-5.8, p = 0.03). Nearly all hospitalized patients with AF received OAC in the secondary prevention of thromboembolic complications. NOACs were used for secondary prevention of stroke among patients with AF in patients with fewer comorbidities.


Identification and characterization of novel MPC1 gene variants causing mitochondrial pyruvate carrier deficiency.
Pyruvate, the end product of glycolysis, is a key metabolic molecule enabling mitochondrial adenosine triphosphate synthesis and takes part in multiple biosynthetic pathways within mitochondria. The mitochondrial pyruvate carrier (MPC) plays a vital role in transporting pyruvate from the cytosol into the organelle. In humans, MPC is a hetero-oligomeric complex formed by the MPC1 and MPC2 paralogs that are both necessary to stabilize each other and form a functional MPC. MPC deficiency (OMIM#614741) due to pathogenic MPC1 variants is a rare autosomal recessive disease involving developmental delay, microcephaly, growth failure, and increased serum lactate and pyruvate. To date, two MPC1 variants in four cases have been reported, though only one with a detailed clinical description. Herein, we report three novel pathogenic MPC1 variants in six patients from three unrelated families, identified within European, Kuwaiti, and Chinese mitochondrial disease patient cohorts, one of whom presented as a Leigh-like syndrome. Functional analysis in primary fibroblasts from the patients revealed decreased expression of MPC1 and MPC2. We rescued pyruvate-driven oxygen consumption rate in patient's fibroblasts by reconstituting with wild-type MPC1. Complementing homozygous MPC1 mutant cDNA with CRISPR-deleted MPC1 C2C12 cells verified the mechanism of variants: unstable MPC complex or ablated pyruvate uptake activity. Furthermore, we showed that glutamine and beta-hydroxybutyrate were alternative substrates to maintain mitochondrial respiration when cells lack pyruvate. In conclusion, we expand the clinical phenotypes and genotypes associated with MPC deficiency, with our studies revealing glutamine as a potential therapy for MPC deficiency.


Alcohol misuse, depressive symptoms, and HIV/STI risks of US Hispanic women.
Alcohol misuse and depressive symptoms have been linked to HIV/STI risk, but studies have rarely included Hispanic women, who have over four times greater HIV incidence than white, non-Hispanic women. Understanding the connections among alcohol misuse, depressive symptoms, and HIV/STI risks may suggest ways to meet specific needs of Hispanic women. This study's objective is to examine the relationships among alcohol misuse, depressive symptoms, and seven HIV/STI risk factors. Five hundred forty-eight US Hispanic women with intake data from a randomized trial were assessed for alcohol misuse (CAGE) and depressive symptoms (CES-D). GZLM and path analyses tested relationships between alcohol misuse or depressive symptoms and HIV/STI risk factors. Self-efficacy and condom use were not related to alcohol misuse or depressive symptoms, but only 15% of women reported consistent condom use. After controlling for demographics, women with alcohol misuse had significantly more perceived HIV/STI risk (OR = 2.15) and better HIV/STI knowledge (β = -.54); and women with depressive symptoms had significantly more perceived HIV/STI risk (OR = 1.76) and worse HIV/STI knowledge (β = .37). Interventions to increase condom use for Hispanic women are needed, regardless of mental disorders. Working with Hispanic women with alcohol misuse or depressive symptoms presents a need (and opportunity) to address issues directly related to HIV/STI risk. Women's health practitioners have an excellent opportunity to reach women by implementing regular screening programs in clinics that serve Hispanic women. For women with high depressive symptoms, poor HIV/STI knowledge should also be addressed. Future studies should test whether integrated and tailored risk reduction interventions affect these factors and lower HIV/STI risk for Hispanic women.


External validation of scores proposed for estimation of survival probability of patients with severe adult respiratory distress syndrome undergoing extracorporeal membrane oxygenation therapy: a retrospective study.
This study was designed as an external validation of the recently proposed Predicting Death for Severe ARDS on V-V ECMO (PRESERVE) score, The respiratory extracorporeal membrane oxygenation survival prediction (RESP) score and a scoring system developed for externally retrieved patients on extracorporeal membrane oxygenation (ECMO) at our institution. All scores are proposed for the estimation of survival probability after ECMO treatment for severe adult respiratory distress syndrome. Data from 51 patients (2008 to 2013) were analyzed in this retrospective single-center study. A calculation of an adapted PRESERVE score, the RESP score as well as the score developed for externally retrieved ECMO patients was performed. Seventy one percent of patients received veno-venous (v-v) and 29% venous-arterial (v-a) ECMO support during the study period. Overall survival at 6 months was 55%, with a 61% survival rate for v-v cannulated patients and a 40% survival rate for v-a cannulated patients. The PRESERVE score discriminated survivors and non-survivors with an area under the curve of 0.67 (95% CI 0.52 to 0.82, P = 0.03). Analyzing survival prediction according to cannulation modus, the PRESERVE score and the RESP score significantly predicted survival for patients on v-v ECMO with an area under the curve of 0.75 (95% CI 0.57 to 0.92, P = 0.01) and 0.81 (95% CI 0.67 to 0.95, P = 0.035), respectively, while the scoring system developed for externally retrieved ECMO patients failed to predict survival in our study population. All scores failed to predict mortality for patients on v-a ECMO. Our single-center validation confirms that the proposed PRESERVE and RESP score predict survival for patients treated with v-v ECMO for severe adult respiratory distress syndrome.