Effect of GAPDH-derived antimicrobial peptides on sensitive yeasts cells: membrane permeability, intracellular pH and H+-influx/-efflux rates.
Saccharomyces cerevisiae secretes antimicrobial peptides (AMPs) derived from glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which induce the death of several non-Saccharomyces yeasts. Previously, we demonstrated that the naturally secreted GAPDH-derived AMPs (i.e. saccharomycin) caused a loss of culturability and decreased the intracellular pH (pHi) of Hanseniaspora guilliermondii cells. In this study, we show that chemically synthesised analogues of saccharomycin also induce a pHi drop and loss of culturability in H. guilliermondii, although to a lesser extent than saccharomycin. To assess the underlying causes of the pHi drop, we evaluated the membrane permeability to H+ cations of H. guilliermondii cells, after being exposed to saccharomycin or its synthetic analogues. Results showed that the H+-efflux decreased by 75.6% and the H+-influx increased by 66.5% in cells exposed to saccharomycin at pH 3.5. Since H+-efflux via H+-ATPase is energy dependent, reduced glucose consumption would decrease ATP production and consequently H+-ATPase activity. However, glucose uptake rates were not affected, suggesting that the AMPs rather than affecting glucose transporters may affect directly the plasma membrane H+-ATPase or increase ATP leakage due to cell membrane disturbance. Thus, our study revealed that both saccharomycin and its synthetic analogues induced cell death of H. guilliermondii by increasing the proton influx and inhibiting the proton efflux.


Validation of the 6-item Evening Chronotype Scale (ECS): a modified version of Composite Scale Morningness.
In a previous study comparing two representative chronotype questionnaires to screen for delayed sleep-phase disorder, six items from the simplified language version of Composite Scale of Morningness (CSM) have been found to be useful and effective for screening evening-type person. In this study, we reverse coded the six items from CSM and named them Evening Chronotype Scale (ECS). The primary aim of this study was to examine the psychometric properties, validity, and test-retest reliability of the ECS when administered on mood disorder patients. The secondary aim was to further examine the relationship between circadian preferences and symptoms of mood disorders. The study sample was of 472 mood disorder patients including major depressive disorder, bipolar disorder I, and bipolar disorder II. The 13-item full version CSM and 6-item ECS were externally validated by self-reported sleep time, wake time, sleep latency, depressive symptoms, hypomanic symptoms, quality of life, and impulsivity. Cronbach's alpha was calculated for the internal consistency of the ECS, and the test-retest reliability analysis was also performed. Our results suggest that the ECS is a reliable and valid instrument to assess circadian preference in mood disorder patients. First, the ECS showed moderate to good internal consistency (Cronbach's alpha = 0.727). Also, it showed external validity comparable to that of the 13-item CSM. Participants who were more evening-oriented according to the ECS slept and woke up later, took longer time to fall asleep, showed more depressive and hypomanic symptoms, and showed lower quality of life and higher impulsivity. As circadian rhythm disruption has been shown to affect the regulation of mood symptoms in patients with mood disorders, assessment of circadian preferences may be crucial in clinical settings. We suggest that ECS appears to be an easy-to-use instrument that is reliable and valid.


The investment case for cervical cancer elimination.
We already know what causes cervical cancer, how to prevent it, and how to treat it, even in resource-constrained settings. Inequitable access to human papillomavirus vaccine for girls and screening and precancer treatment for women in low- and middle-income countries is unacceptable on ethical, social, and financial grounds. The burden of cervical cancer falls on the poor and extends beyond the narrow bounds of the family, affecting national economic development and community life, as family resources are drained and poverty tightens its grip. Proven solutions are available and the priorities for the next few years are clear, as shown by the papers in this Supplement. Sustained political commitment and strategic investments in cervical cancer prevention can not only save millions of lives over the next 10 years, but can also pave the way for the broader fight against all cancers.


Temporal cAMP Signaling Selectivity by Natural and Synthetic MC4R Agonists.
The melanocortin-4 receptor (MC4R) is a G protein-coupled receptor expressed in the brain, where it controls energy balance through pathways including α-melanocyte-stimulating hormone (α-MSH)-dependent signaling. We have reported that the MC4R can exist in an active conformation that signals constitutively by increasing cAMP levels in the absence of receptor desensitization. We asked whether synthetic MC4R agonists differ in their ability to increase intracellular cAMP over time in Neuro2A cells expressing endogenous MC4R and exogenous, epitope-tagged hemagglutinin-MC4R-green fluorescent protein. By analyzing intracellular cAMP in a temporally resolved Förster resonance energy transfer assay, we show that withdrawal of α-MSH leads to a quick reversal of cAMP induction. By contrast, the synthetic agonist melanotan II (MTII) induces a cAMP signal that persists for at least 1 hour after removal of MTII from the medium and cannot be antagonized by agouti related protein. Similarly, in mHypoE-42 immortalized hypothalamic neurons, MTII, but not α-MSH, induced persistent AMP kinase signal, which occurs downstream of increased cAMP. By using a fluorescence recovery after photobleaching assay, it appears that the receptor exposed to MTII continues to signal after being internalized. Similar to MTII, the synthetic MC4R agonists, THIQ and BIM-22511, but not LY2112688, induced prolonged cAMP signaling after agonist withdrawal. However, agonist-exposed MC4R desensitized to the same extent, regardless of the ligand used and regardless of differences in receptor intracellular retention kinetics. In conclusion, α-MSH and LY2112688, when compared with MTII, THIQ, and BIM-22511, vary in the duration of the acute cAMP response, showing distinct temporal signaling selectivity, possibly linked to specific cell compartments from which cAMP signals may originate.


Endovascular Repair of Primary Thoracic Aortic Mural Thrombus Following Upper Limb Embolization.
We report the case of a 41-year-old female who presented with left upper limb embolization due to primary thoracic aortic mural thrombus; this latter represented an uncommon condition with difficult diagnosis and a high rate of life-threatening complications. Upper extremities embolization is extremely rare because it usually occurs in the lower limbs. Management strategy is still controversial, and no clear guidelines indicate superiority of either conservative or invasive treatment approach to date. Our report illustrates how endovascular exclusion of thoracic aortic mural thrombus has the advantage to be a low-risk procedure that represents a definitive therapy.


Identification of putative substrates for the periplasmic chaperone YfgM in Escherichia coli using quantitative proteomics.
How proteins are trafficked, folded, and assembled into functional units in the cell envelope of Gram-negative bacteria is of significant interest. A number of chaperones have been identified, however, the molecular roles of these chaperones are often enigmatic because it has been challenging to assign substrates. Recently we discovered a novel periplasmic chaperone, called YfgM, which associates with PpiD and the SecYEG translocon and operates in a network that contains Skp and SurA. The aim of the study presented here was to identify putative substrates of YfgM. We reasoned that substrates would be incorrectly folded or trafficked when YfgM was absent from the cell, and thus more prone to proteolysis (the loss-of-function rationale). We therefore used a comparative proteomic approach to identify cell envelope proteins that were lower in abundance in a strain lacking yfgM, and strains lacking yfgM together with either skp or surA. Sixteen putative substrates were identified. The list contained nine inner membrane proteins (CusS, EvgS, MalF, OsmC, TdcB, TdcC, WrbA, YfhB, and YtfH) and seven periplasmic proteins (HdeA, HdeB, AnsB, Ggt, MalE, YcgK, and YnjE), but it did not include any lipoproteins or outer membrane proteins. Significantly, AnsB (an asparaginase) and HdeB (a protein involved in the acid stress response), were lower in abundance in all three strains lacking yfgM. For both genes, we ruled out the possibility that they were transcriptionally down-regulated, so it is highly likely that the corresponding proteins are misfolded/mistargeted and turned-over in the absence of YfgM. For HdeB we validated this conclusion in a pulse-chase experiment. The identification of HdeB and other cell envelope proteins as potential substrates will be a valuable resource for follow-up experiments that aim to delineate molecular the function of YfgM.


Rearrangements of F-actin arrays in growing cells of intact maize root apex tissues: a major developmental switch occurs in the postmitotic transition region.
Immunofluorescence labeling, using a monoclonal antibody developed against actin, revealed the relative abundance and rearrangements of F-actin arrays which occur in cells of the maize root apex as they make the developmental transition from proliferative growth in the meristem to a non-proliferative state in more mature root parts, and during the concomitant process of tissue differentiation. Cells in both the root cap and the quiescent center are depleted of F-actin, whereas it is abundant in cells of the central cylinder but less so in the cortex. The cortical cytoplasm associated with the endwalls of both mitotic and postomitotic cells is characterized by a more intense reactivity to the actin antibody than the longitudinal side walls. A major change in F-actin arrangement occurs in the transitional growth region interpolated between the meristem and the zone of rapid cell elongation. The location and nature of these F-actin rearrangements within the root suggest that the F-actin system might be involved in generating a force associated with the developmental transition of cells from their slow near-isotropic mode of growth close to the base of the meristem, to rapid anisotropic growth which is characteristic of the zone of cell elongation. This attraction notion was strongly supported using specific inhibitors of F-actin and myosin.


Prokaryotic expression, purification and characterization of human cyclooxygenase-2.
Cyclooxygenase-2 (COX-2) is a key enzyme which catalyzes the conversion of arachidonic acid (AA) into prostaglandins (PGs). It plays an important role in pathophysiological processes, such as tumorigenesis, angiogenesis, inflammation and tumor cell drug resistance. Therefore, COX-2 has been viewed as an important target for cancer therapy. The preparation of COX-2 protein is an important initial step for the subsequent development of COX-2 inhibitors. In this study, we report a strategy to heterologously express truncated human COX-2 (trCOX-2) in Escherichia coli (E. coli) BL21(DE3) host cells. Following denaturation, purification and renaturation, we successfully obtained enzymatically active trCOX-2 containing 257 residues of the C-terminus. Homology modeling and molecular docking analyses revealed that trCOX-2 retained the predicted 3D catalytic domain structure and AA could still bind to its hydrophobic groove. Western blot analysis and ELISA indicated that the trCOX-2 still retained its characteristic antigenicity and binding activity, while COX assays revealed that trCOX-2 maintained its enzyme activity. On the whole, in this study, we provided a novel method to isolate trCOX-2 possessing AA binding and catalytic activities. This study thus lays a foundation to facilitate further investigations of COX-2 and offers a valuable method with which to achieve the prokaryotic expression of a eukaryotic membrane protein.


Safety and efficacy of a proteolytic enzyme for enzymatic burn debridement: a preliminary report.
A prospective, non-comparative study design was used to describe our experience with a bromelain-derived debriding agent, Debridase, in 130 patients with 332 deep second degree and third degree burns treated between 1984 and 1999. Debridase was applied after saturating the burns with a moist dressing for 2-24h. Debridase was applied for a period of 4h under an occlusive dressing. Mean patient age was 18.6 +/- 19.3, 42 (32.3%) were female, and 63 (48.5%) were children under age 18. Most burns were small. Debridase was applied once in 241 (72.6%) of the 332 wounds, twice in 67 (20.18%) cases, three times in 12 (3.61%) cases, and four times in 2 (0.6%) cases. The percentage debridement by number of applications was 89 +/- 21% for a single application, 77 +/- 27% for two, and 62 +/- 27% for three Debridase applications, respectively. There were no significant adverse events. The availability of a fast acting, reliable and complication-free enzymatic debriding agent may open new horizons and provide a new treatment modality for burns.


[A simultaneous operation of closure of multiple congenital coronary artery-pulmonary artery fistulas and aortocoronary bypass grafting--a case report].
A 59-year-old male was admitted because of severe chest pain and diagnosed as inferior myocardial infarction by ECG and enzymologically, who had a Levine grade II continuous murmur in the left second intercostal space at the left sternal border. Cardiac catheterization revealed a 8% left to right shunt at pulmonary artery. Selective coronary cineangiography revealed left anterior descending-to-main pulmonary artery and left circumflex-to-main pulmonary artery fistulas, and severe atherosclerotic stenosis at right coronary and left anterior descending arteries. Operation was performed simultaneously, closure of two drainage orifices of the fistulous vessels through pulmonary arteriotomy and aortocoronary bypass grafting to left anterior descending under cardiopulmonary bypass. The postoperative course was uneventful, and the murmur was disappeared.


Household conditions, COVID-19, and equity: Insight from two nationally representative surveys.
With people across the United States spending increased time at home since the emergence of COVID-19, housing characteristics may have an even greater impact on health. Therefore, we assessed associations between household conditions and COVID-19 experiences. We used data from two nationally representative surveys: the Tufts Equity Study (TES; n = 1449 in 2021; n = 1831 in 2022) and the Household Pulse Survey (HPS; n = 147,380 in 2021; n = 62,826 in 2022). In the TES, housing conditions were characterized by heating/cooling methods; smoking inside the home; visible water damage/mold; age of housing unit; and self-reported concern about various environmental factors. In TES and HPS, household size was assessed. Accounting for sampling weights, we examined associations between each housing exposure and COVID-19 outcomes (diagnosis, vaccination) using separate logistic regression models with covariates selected based on an evidence-based directed acyclic graph. Having had COVID-19 was more likely among people who reported poor physical housing condition (odds ratio [OR] = 2.32; 95% confidence interval [CI] = 1.17-4.59; 2021), visible water damage or mold/musty smells (OR = 1.50; 95% CI = 1.10-2.03; 2022), and larger household size (5+ versus 1-2 people; OR = 1.53, 95% CI = 1.34-1.75, HPS 2022). COVID-19 vaccination was less likely among participants who reported smoke exposure inside the home (OR = 0.53; 95% CI = 0.31-0.90; 2022), poor water quality (OR = 0.42; 95% CI = 0.21-0.85; 2021), noise from industrial activity/construction (OR = 0.44; 95% CI = 0.19-0.99; 2022), and larger household size (OR = 0.57; 95% CI = 0.46-0.71; HPS 2022). Vaccination was also positively associated with poor indoor air quality (OR = 1.96; 95% CI = 1.02-3.72; 2022) and poor physical housing condition (OR = 2.27; 95% CI = 1.01-5.13; 2022). Certain heating/cooling sources were associated with COVID-19 outcomes. Our study found poor housing conditions associated with increased COVID-19 burden, which may be driven by systemic disparities in housing, healthcare, and financial access to resources during the COVID-19 pandemic.


Disseminated Mycobacterium tuberculosis: An Unusual Presentation with Associated Hemophagocytic Lymphohistiocytosis.
Hemophagocytic lymphohistiocytosis (HLH) is a rare, potentially fatal, and systemic hyperinflammatory syndrome with exacerbated and uncontrolled activation of histiocytes and lymphocytes against mature cells. Secondary HLH can occur in association with a myriad of underlying infections or malignancies. Our patient is a 38-year-old male prisoner with poorly controlled diabetes and no known other medical conditions. He was referred to our emergency department with three-week history of worsening malaise, weight loss, fever, bruising, and shortness of breath; imaging showed pneumomediastinum, lung nodule, and adrenal mass. Biopsy of the lung nodule revealed acid-fast bacilli. Furthermore, bone marrow biopsy showed foci of necrosis with associated acid-fast bacilli and hemophagocytosis highlighted by CD163 stain; consequently, secondary HLH was suggested. Hence, lab results were reviewed and found to satisfy five of the eight secondary HLH criteria. Moreover, ferritin was >10,000 ng/ml, which has been suggested to be highly suspicious for HLH. The patient was started on anti-MAC therapy. Unfortunately, the patient's status declined rapidly; he developed multi-organ failure and succumbed to disease. Later, his culture confirmed Mycobacterium tuberculosis. In conclusion, we presented a rare and challenging case of secondary HLH associated with disseminated Mycobacterium tuberculosis. A high index of suspicion is required for early diagnosis and treatment, and pathologists should be aware of Mycobacterium tuberculosis' association with secondary HLH.


Biomechanical maturation of joint dynamics during early childhood: updated conclusions.
Dynamic parameters have been commonly explored to characterize the biomechanical maturation of children's gaits, i.e., age-revealing joint moment and power patterns similar to adult patterns. However, the literature revealed a large disparity of conclusions about maturation depending on the study, which was most likely due to an inappropriate scaling strategy and uncontrolled walking speed. With the first years of independent walking, a large growth in height and a large variability of dimensionless walking speed are observed. Moreover, the dynamic parameters were not well studied during early childhood. In the present study, seventy-five healthy children between 1 and 6 years of age were assessed during gait trials at a self-selected speed. Four hundred and sixty-two gait trials constituting five age groups with comparable dimensionless walking speeds were selected. 3D joint moments and the power of the lower limbs were computed and expressed using a dimensionless scaling strategy (according to body weight, leg length and the acceleration of gravity). Statistical analysis was performed to examine inter-group differences. Based on the current results, we concluded the biomechanical maturation of joint dynamics occurred around an age of 4 years for the ankle and between 6 and 7 years for the knee and the hip. Moreover, age group comparisons seemed more appropriate in young children using both the dimensionless strategy and a similar walking speed. Future investigations will be conducted on an older population (i.e., adding children older than 6 years) to clearly define the status of knee and hip biomechanical maturation.


Detection and monitoring of vasospasm and delayed cerebral ischemia: a review and assessment of the literature.
Delayed cerebral ischemia (DCI) after subarachnoid hemorrhage can be evaluated using clinical assessment, non-invasive and invasive techniques. An electronic literature search was conducted on English-language articles investigating DCI in human subjects with subarachnoid hemorrhage. A total of 31 relevant papers were identified evaluating the role of clinical assessment, transcranial Doppler, computed tomographic angiography, and computed tomographic perfusion. Clinical assessment by bedside evaluations is limited, especially in patients initially in poorer clinical condition or who are receiving sedative medication for whom deterioration may be more difficult to identify. Transcranial Doppler is a useful screening tool for middle cerebral artery vasospasm, with less utility in evaluating other intracranial vessels. Computed tomographic angiography correlates well with digital subtraction angiography. Computed tomographic perfusion may help predict DCI when used early or identify DCI when used later.


[Fibromyalgia and trigger points].
Trigger points in chronic pain and myofascial syndromes are often localized at a distance from the painful area. Infiltration of trigger points with Bupivacaine 0.5% greatly reduces pain and can eliminate it with no need of any other analgesic therapy.


Typical bulbar ALS can be linked to GARS mutation.
Background: Amyotrophic lateral sclerosis is the most frequent motor neuron disorders (MND) in adults. The role of genetic factors is worldwide accepted, and currently, more than 30 genes have been linked to this disease. Genetics was also the matter of numerous studies in distal hereditary motor neuropathies (dHMN). GARS is classically linked to a predominant dHMN and, until now, no mutation has been described in GARS in other MND. Case Report: We report the case of a 70-year-old woman who developed a classical bulbar ALS phenotype. Owing to his familial history of ALS, a genetic screening was performed excluding the main genes linked to ALS and revealing a heterozygous missense mutation in GARS gene with a high probability of pathogenicity. Conclusion: This first description of mutation in GARS in ALS, extends once more the genetic overlap between ALS and other MND.


Role of calcium in postjunctional supersensitivity.
Several hours to days after an animal is given reserpine its cardiovascular system becomes supersensitive to catecholamines. This phenomenon can be demonstrated for vascular tissue by in vitro experiments. This type of supersensitivity has been termed "nonspecific" because the tissue is supersensitive to varied agonists, including acetylcholine, calcium, potassium, and the catecholamines. Animals that have been treated with reserpine have been found to have a transient decrease in the calcium content of their vascular tissue. The responses to norepinephrine of aortic strips from reserpine-treated rabbits, even though of greater magnitude than those of untreated aortic strips, were less dependent on extracellular calcium than responses of strips from untreated rabbits. On the other hand, the responses to potassium were more dependent on extracellular calcium. In addition, when aortic strips from reserpine-pretreated animals are subjected to potassium in a calcium-free medium, they are not supersensitive to the ion. When aortic strips are placed in a calcium-free, depolarizing medium they are still supersensitive to norepinephrine and isoproterenol but not to acetylcholine. Tension decline and 45Ca efflux studies suggest that reserpine-treated tissues retain longer than untreated tissues a calcium fraction involved in contraction. It is concluded that reserpine alters binding or movement of calcium in at least two sites. The lack of supersensitivity to acetylcholine and potassium in a calcium-free medium indicates an effect of reserpine (or the loss of adrenergic transmitter) on the utilization of extracellular calcium, while some other site must be involved in at least part of the supersensitivity to the catecholamines.


Smooth bistable S-systems.
S-systems have been used as models of biochemical systems for over 30 years. One of their hallmarks is that, although they are highly non-linear, their steady states are characterised by linear equations. This allows streamlined analyses of stability, sensitivities and gains as well as objective, mathematically controlled comparisons of similar model designs. Regular S-systems have a unique steady state at which none of the system variables is zero. This makes it difficult to represent switching phenomena, as they occur, for instance, in the expression of genes, cell cycle phenomena and signal transduction. Previously, two strategies were proposed to account for switches. One was based on a technique called recasting, which permits the modelling of any differentiable non-linearities, including bistability, but typically does not allow steady-state analyses based on linear equations. The second strategy formulated the switching system in a piece-wise fashion, where each piece consisted of a regular S-system. A representation gleaned from a simplified form of recasting is proposed and it is possible to divide the characterisation of the steady states into two phases, the first of which is linear, whereas the other is non-linear, but easy to execute. The article discusses a representative pathway with two stable states and one unstable state. The pathway model exhibits strong separation between the stable states as well as hysteresis.


Colorimetric detection of mercury(II) ion using unmodified silver nanoparticles and mercury-specific oligonucleotides.
A sensitive and selective colorimetric detection method for mercury(II) has been well-established in this paper. It was based on the conformation change of mercury-specific oligonucleotides (MSO) from random coil structure to hairpin structure upon the addition of Hg(2+) and the phenomenon of salt-induced unmodified silver nanoparticles (AgNPs) aggregation. The calibration curve showed that the net absorption ratio value at 395 and 570 nm increased linearly over the Hg(2+) concentration range of 25-500 nM with a limit of detection of 17 nM. The other environmentally relevant metal ions did not interfere with the determination of Hg(2+).


Experience with chromogenic substrates in studies of clotting and fibrinolytic systems.
Experiences in the application of chromogenic substrates for the evaluation of clotting variables are reported. The use of a special buffer system enables the determination of factor Xa by the thrombin substrate Chromozym TH. Prothrombin in plasma can be determined using the substrate S-2238 after activation with factor Xa or Ecarin. Factor VII is activated with thromboplastin and is estimated indirectly via factor Xa activity. Comparison of the amidolytic method for factor VII with prothrombin times of patients on oral anticoagulants shows good correlation. Chromogenic substrates can be also used for determining platelet factor 3 (S-2238), plasminogen and alpha 2-antiplasmin.


The new combination of oxygen saturation with age shock index predicts the outcome of COVID-19 pneumonia.
Emergency departments around the world have been struggling to deal with patients with COVID-19 and presumed COVID-19. Triaging patients who need further medical support is the key matter to emergency physicians as the delay of proper treatment may worsen the results. The aim of this study was to validate the ability of age shock index and hypoxia-age-shock index at the time of presentation to the emergency department to predict case fatality in patients with COVID-19 pneumonia. We only included patients who had COVID-19-associated pneumonia who needed in-hospital treatment. The vital signs and oxygen saturation used in the study were collected, especially from the triage sector, before patients were given supplemental oxygen. A total of 241 patients enrolled in the study. The case fatality rate was 27%. The median age of the study samples was 78 (66-86) years with 133 male and 108 female patients. Hypoxia-age-shock index showed the best performance in analysis (odds ratio 15.1, 95% confidence interval: 5.1-44.4; adjusted odds ratio 8.6, 95% confidence interval: 2.8-26.8). The hypoxia-age-shock index was a strong predictor for in-hospital mortality of COVID-19 pneumonia. Furthermore, when it was compared with age shock index, hypoxia-age-shock index showed better performance in predicting fatality of the disease.


Costs of Implementing Teen Dating Violence and Youth Violence Prevention Strategies: Evidence From 5 CDC-Funded Local Health Departments.
In 2016, the Centers for Disease Control and Prevention supported 5 local health departments (LHDs) to implement teen dating violence and youth violence primary prevention strategies across multiple levels of the social-ecological model and build capacity for the expansion of such prevention efforts at the local level. The objective of this study was to estimate the total cost of implementing primary prevention strategies for all LHDs across 3 years of program implementation. We used a microcosting analytic approach to identify resources and compute costs for all prevention strategies implemented by LHDs. We computed the total program cost, total and average cost per strategy by social-ecological model level, and average cost of implementation per participant served by the program. All costs were inflated via the monthly Consumer Price Index and reported in August 2020 dollars. For 3 years of program implementation, the total estimated cost of implementing teen dating violence and youth violence primary prevention strategies was >$7.1 million across all 5 LHDs. The largest shares of program-related costs were program staff (55.9%-57.0%) and contracts (22.4%-25.5%). Among prevention strategies, the largest share of total costs was for strategies implemented at the community level of the social-ecological model (42.8%). The findings from this analysis provide a first look at the total costs of implementing comprehensive teen dating violence and youth violence primary prevention strategies and serve as a foundation for investments in local violence prevention funding for young people.


[Arrhythmia in patients on dialysis treatment for chronic renal failure].
In 6 patients treated with repeated peritoneal dialyses 48-hour ECG monitoring was carried out. In no patient significant heart rhythm disturbances were demonstrated during the dialysis and 24 hours after its completion. On the ground of pathological results of Valsalva's manoeuvre function disturbances of the autonomic nervous system were disclosed but these showed no correlation with premature ventricular and supraventricular++ ectopic beats appearing periodically in some patients. The study showed that under conditions of sufficient control of electrolyte balance (especially potassium) the patients treated with peritoneal dialyses are not a group at risk for arrhythmia development.


[Programmed hemodialysis in middle and old age].
28 patients treated by programmed hemodialysis (PH) were followed up from 1985 to 1991. All the patients were over 60 years old. 16 patients died within month 1-60 since PH initiation. Overall PH duration for the whole group reached 24.6 +/- 3.58 months. Pretreatment urea and creatinine in plasma of senile patients were significantly lower than in young patients not resulting, though, in uremia reduction. The findings show that it is not valid to consider creatinine a determinant for starting hemodialysis in senile patients. Despite multimorbidity, more rapid progression of atherosclerosis and complicated establishment of the vascular approach, senile patients successfully adapt to PH regimen, need less numerous weekly PH hours. By anemia manifestations, incidence of hyperparathyroidism and polyneuropathy, senile patients did not differ much from their younger counterparts.


1,3,5,8-Tetrasubstituted 1,3,4-Benzotriazepin-2-one Scaffolds for β-Turn Mimicry without Stereogenic Carbon Centers: Synthesis and Conformational Analysis.
Topological mimicry of peptide β-turn secondary structures has been investigated using a 1,3,5,8-tetrasubstituted 1,3,4-benzotriazepin-2-one scaffold. Approaches were conceived for the synthesis of tetrasubstituted benzotriazepinones from 4-acetyl-3-aminobenzoate based on aza-amino acid chemistry and different orthogonal protection strategies. Installation of an 8-position carboxylate on the aromatic ring enabled a diverse array of substituents to be introduced for mimicry of the i-position residue. Benzotriazepin-2-one crystallization and X-ray analysis demonstrated that in spite the absence of a stereogenic carbon center, the scaffold could serve as type I and I' β-turn mimics, because pyramidalization of the N3-nitrogen in the benzotriazepin-2-one provides potential for adoptive chirality. 1,3,5,8-Tetrasubstituted 1,3,4-benzotriazepin-2-one scaffolds offer interesting potential for the cost-effective synthesis of nonpeptide β-turn surrogates for peptide mimicry in various recognition events.


Are dendrites in Drosophila homologous to vertebrate dendrites?
Dendrites represent arborising neurites in both vertebrates and invertebrates. However, in vertebrates, dendrites develop on neuronal cell bodies, whereas in higher invertebrates, they arise from very different neuronal structures, the primary neurites, which also form the axons. Is this anatomical difference paralleled by principal developmental and/or physiological differences? We address this question by focussing on one cellular model, motorneurons of Drosophila and characterise the compartmentalisation of these cells. We find that motorneuronal dendrites of Drosophila share with typical vertebrate dendrites that they lack presynaptic but harbour postsynaptic proteins, display calcium elevation upon excitation, have distinct cytoskeletal features, develop later than axons and are preceded by restricted localisation of Par6-complex proteins. Furthermore, we demonstrate in situ and culture that Drosophila dendrites can be shifted from the primary neurite to their soma, i.e. into vertebrate-like positions. Integrating these different lines of argumentation, we propose that dendrites in vertebrates and higher invertebrates have a common origin, and differences in dendrite location can be explained through translocation of neuronal cell bodies introduced during the evolutionary process by which arthropods and vertebrates diverged from a common urbilaterian ancestor. Implications of these findings for studies of dendrite development, neuronal polarity, transport and evolution are discussed.


Comparative hydrodynamic and nanoscale imaging study on the interactions of teicoplanin-A2 and bovine submaxillary mucin as a model ocular mucin.
Glycopeptide antibiotics are regularly used in ophthalmology to treat infections of Gram-positive bacteria. Aggregative interactions of antibiotics with mucins however can lead to long exposure and increases the risk of resistant species. This study focuses on the evaluation of potential interactions of the last line of defence glycopeptide antibiotic teicoplanin with an ocular mucin model using precision matrix free hydrodynamic and microscopic techniques: sedimentation velocity in the analytical ultracentrifuge (SV-AUC), dynamic light scattering (DLS) and atomic force microscopy (AFM). For the mixtures of teicoplanin at higher doses (1.25 mg/mL and 12.5 mg/mL), it was shown to interact and aggregate with bovine submaxillary mucin (BSM) in the distributions of both sedimentation coefficients by SV-AUC and hydrodynamic radii by DLS. The presence of aggregates was confirmed by AFM for higher concentrations. We suggest that teicoplanin eye drop formulations should be delivered at concentrations of < 1.25 mg/mL to avoid potentially harmful aggregations.


Neonatal Liver Failure and Congenital Cirrhosis due to Gestational Alloimmune Liver Disease: A Case Report and Literature Review.
Neonatal liver failure (NLF) is a major cause of neonatal morbidity and mortality, presenting as acute liver failure and/or congenital cirrhosis. Many affected patients show antenatal signs of fetal injury. There are several causes of NLF and early diagnosis is mandatory to elucidate the etiology and determine a specific treatment or the best management strategy. Gestational alloimmune liver disease associated with neonatal hemochromatosis (GALD-NH) is a rare but potentially treatable cause of NLF. It should be considered in any neonate with fetal signs of disease and postnatal signs of liver failure with no other identifiable causes. GALD-NH is often diagnosed late and patients are therefore referred late to specialized centers, delaying treatment. This case highlights the consequences of late diagnosis and treatment of GALD-NH and emphasizes the importance of a high grade of suspicion of this disease in order to refer the patient to a specialized center soon enough to perform the appropriate treatment.


Complete denture success for patients and dentists.
The huge prevalence of tooth decay and the gradual ageing of populations in the developed world have combined to produce a steady increase in the need for complete denture treatment. To achieve successful treatment, it is vital to consider a number of issues throughout the denture process. Before treatment even begins, the patient's motivation for denture treatment and emotional attitude towards dentures must be evaluated. Patients will thereby gain realistic expectations of what can and cannot be achieved, and dentists will understand what the patient really wants. Afterwards, the dentist must work with the patient to help achieve success in difficult areas such as neuromuscular control, mastication and speech. By learning to handle patient complaints positively, dentists can educate patients to solve their own problems in future. Finally, patients must be informed that continued success depends on regular denture maintenance at home combined with periodic consultation with the dentist.


CX-4945, an orally bioavailable selective inhibitor of protein kinase CK2, inhibits prosurvival and angiogenic signaling and exhibits antitumor efficacy.
Malignant transformation and maintenance of the malignant phenotype depends on oncogenic and non-oncogenic proteins that are essential to mediate oncogene signaling and to support the altered physiologic demands induced by transformation. Protein kinase CK2 supports key prosurvival signaling pathways and represents a prototypical non-oncogene. In this study, we describe CX-4945, a potent and selective orally bioavailable small molecule inhibitor of CK2. The antiproliferative activity of CX-4945 against cancer cells correlated with expression levels of the CK2α catalytic subunit. Attenuation of PI3K/Akt signaling by CX-4945 was evidenced by dephosphorylation of Akt on the CK2-specific S129 site and the canonical S473 and T308 regulatory sites. CX-4945 caused cell-cycle arrest and selectively induced apoptosis in cancer cells relative to normal cells. In models of angiogenesis, CX-4945 inhibited human umbilical vein endothelial cell migration, tube formation, and blocked CK2-dependent hypoxia-induced factor 1 alpha (HIF-1α) transcription in cancer cells. When administered orally in murine xenograft models, CX-4945 was well tolerated and demonstrated robust antitumor activity with concomitant reductions of the mechanism-based biomarker phospho-p21 (T145). The observed antiproliferative and anti-angiogenic responses to CX-4945 in tumor cells and endothelial cells collectively illustrate that this compound exerts its antitumor effects through inhibition of CK2-dependent signaling in multiple pathways. Finally, CX-4945 is the first orally bioavailable small molecule inhibitor of CK2 to advance into human clinical trials, thereby paving the way for an entirely new class of targeted treatment for cancer.


Effects of rimonabant on the development of single dose-induced behavioral sensitization to ethanol, morphine and cocaine in mice.
The endocannabinoid system has been implicated in the neurobiological mechanism underlying drug addiction, especially the primary rewarding dopamine-dependent processes. Therefore, endocannabinoid receptor antagonists, such as the CB1 cannabinoid antagonist rimonabant, have been proposed as candidates for preventive addiction therapies. Investigate the possible involvement of CB1 receptors in the development of behavioral sensitization to ethanol, morphine and cocaine in mice. We compared the effects of different doses of rimonabant (0.3, 1, 3 and 10mg/kg) on spontaneous locomotor activity in the open-field, hyperlocomotion induced by acute administration of ethanol (1.8g/kg), morphine (20mg/kg) or cocaine (10mg/kg) and on subsequent drug-induced locomotor sensitization using a two-injection protocol in mice. We also investigated a possible depressive-like effect of an acute rimonabant challenge at the highest dose and its potential anxiogenic property. At the highest dose, rimonabant abolished ethanol- and cocaine-induced hyperlocomotion and behavioral sensitization without modifying spontaneous and central locomotor activity or inducing depressive-like behavior on the forced swim test in mice. The other doses of rimonabant also selectively blocked acute ethanol-induced central hyperlocomotion. Although rimonabant at 0.3 and 1mg/kg potentiated the central hyperlocomotion induced by acute morphine injection, it was effective in attenuating morphine-induced behavioral sensitization at all doses. Because the neural basis of behavioral sensitization has been proposed to correspond to some components of addiction, our findings indicate that the endocannabinoid system might be involved in ethanol, cocaine and morphine abuse.


Serum cystine aminopeptidase and leucine aminopeptidase activity in women with benign and malignant uterine and ovarian tumors.
The serum enzymatic activities of cystine aminopeptidase and leucine aminopeptidase were measured in a group of 113 patients of whom 90 had benign uterine or ovarian tumors, and 23 had cancer of the endometrium or ovary. Thirty healthy nonpregnant women and 260 women at different stages of normal pregnancy served as control groups. The presence of pregnancy-specific enzymes in women with uterine or ovarian tumors showed once again that similar processes occur during pregnancy and malignancy. When ovarian or uterine malignancy is suspected on clinical examination, determination of the activities of these enzymes in serum may be of diagnostic value.


Challenging the principle of utility as a barrier for wider use of liver transplantation for hepatocellular cancer.
Although transplant benefit appears superior for patients with advanced hepatocellular cancer (HCC), liver transplantation remains limited to selected low-risk HCC patients to keep their outcomes similar to heterogeneous group of non-HCC patients. The purpose of this study was to assess the rationale for current policy of restricting access to liver transplantation to minority of HCC patients based on utility principle. This retrospective cohort study comprised 1246 liver transplant recipients, including 206 HCC and 1040 non-HCC patients. Patient survival was the primary outcome measure. Patients with HCC and benign diseases were divided into low-, moderate-, and high-risk subgroups basing on independent risk factors for disease-free survival and model for end-stage liver disease (MELD) score (<30, 30-40, >40), respectively. MELD (p < 0.001) and presence of HCC (p = 0.008) were independent risk factors for early and late mortality, respectively. Total tumor volume (p = 0.008) and alpha-fetoprotein (p = 0.013) were independent predictors of recurrence and mortality used for division of HCC patients into low-, moderate-, and high-risk subgroups, with disease-free survival rates of 74.9% (5 years), 51.7% (5 years), and 8.0% (3 years), respectively (p < 0.001). There were no differences in 5-year overall survival between low-risk HCC (74.9%) and non-HCC (81.9%) patients (p = 0.210), moderate-risk HCC (63.3%) and non-HCC (68.0%) patients (p = 0.372), and high-risk HCC (55.0%) and non-HCC (56.0%) patients (p = 0.559). The principle of utility is unequally applied for restriction of access to liver transplantation for HCC patients. The results provide rationale for discussion on reinitiation of liver transplantation for advanced HCCs.


The Diagnostic Accuracy and Prognostic Value of Lung ultrasound in Suspected COVID-19 a retrospective service evaluation.
We read with interest the paper from Knight et al in Acute Medicine1 in particular the use of a lung ultrasound (LUS) score to predict outcome in patients with suspected COVID-19. LUS has been shown to be useful in the diagnosis and prognosis for COVID-19 by other authors. We have carried out a service evaluation project on our data from East Surrey Hospital looking into prognostic and diagnostic performance of LUS in suspected COVID-19. In contrast to the data used by Knight et al we had discharge diagnosis data available which allowed us to split the cohort into patients with COVID-19 and patients with other diagnoses and compare the LUS score between the two groups.


Reduced cerebral injury in CRH-R1 deficient mice after focal ischemia: a potential link to microglia and atrocytes that express CRH-R1.
Corticotropin releasing hormone (CRH) and its family of related peptides are involved in regulating physiologic responses to multiple stressors, including stroke. Although CRH has been implicated in the exacerbation of injury after stroke, the mechanism remains unclear. After ischemia, both excitotoxic damage and inflammation contribute to the pathology of stroke. CRH is known to potentiate excitotoxic damage in the brain and has been shown to modulate inflammatory responses in the periphery. Here the present authors examine the relative contribution of the two known CRH receptors, CRH-R1 and CRH-R2, to ischemic injury using CRH receptor knockout mice. These results implicate CRH-R1 as the primary mediator of ischemic injury in this mouse model of stroke. In addition, the authors examine a potential role for CRH in inflammatory injury after stroke by identifying functional CRH receptors on astrocytes and microglia, which are cells that are known to be involved in brain inflammation. By single cell PCR, the authors show that microglia and astrocytes express mRNA for both CRH-R1 and CRH-R2. However, CRH-R1 is the primary mediator of cAMP accumulation in response to CRH peptides in these cells. The authors suggest that astrocytes and microglia are cellular targets of CRH, which could serve as a link between CRH and inflammatory responses in ischemic injury via CRH-R1.


Pharmacologic interventions in chronic obstructive pulmonary disease: bronchodilators.
Chronic obstructive pulmonary disease (COPD) is a treatable disease characterized by progressive airflow limitation. Prevention of disease progression, improvement of symptoms, exercise tolerance, health status, and decrease in exacerbations and in mortality are the main goals of the management of COPD. Bronchodilators play a pivotal role in the treatment of symptomatic patients with COPD. Inhaled short-acting bronchodilators are currently recommended for rescue of symptoms in patients with mild disease, whereas inhaled long-acting bronchodilators are recommended as first-line agents for maintenance therapy in patients with moderate and severe disease and those with daily symptoms. Long-acting bronchodilators improve symptoms, exercise tolerance, and health status, and reduce exacerbations in patients COPD. However, their effects on long-term decline in lung function and mortality are currently under investigation. When symptoms are not sufficiently controlled by the use of one bronchodilator, combining bronchodilators of different classes may be a more effective approach. In fact, recent evidence supports the regular use of a combination of a long-acting beta2-adrenoceptor agonist and a long-acting anticholinergic agent in patients with severe COPD. Combining a long-acting beta2-adrenoceptor agonist with an inhaled corticosteroid has also been shown to be more effective than the use of either agent alone. The use of theophylline has declined in recent years because of its narrow therapeutic index, and should be reserved as a third-line option in patients with very severe disease. Several novel bronchodilators are now in different stages of development for use alone or in combination with other agents.


Light emission of sonoluminescent bubbles containing a rare gas and water vapor.
We present numerical simulations of sonoluminescent rare-gas bubbles in water, which account for (i) time variations of the water vapor content, (ii) chemical reactions, and (iii) the ionization of the rare gas and the H2O dissociation products. Peak temperatures exceed 10 000 K at densities of a few hundred amagat ( approximately 10(28) particles per m(3)). The gas mixture in the bubble is weakly ionized. Our model accounts for the light emission by electron-atom, electron-ion, and ion-atom bremsstrahlung, recombination radiation, and radiative attachment of electrons to hydrogen and oxygen atoms, which are all more or less important for single bubble sonoluminescence. Spectral shapes, spectral intensities, and durations of the light pulses are computed for helium, argon, and xenon bubbles. We generally obtain good agreement with the observations for photon numbers and pulse durations. Some calculated spectral profiles agree, however, less well with observations, especially in the case of the low water temperature and for helium bubbles. We try to identify the reasons why computed and observed spectral profiles might discernibly differ when all other computed features considered here seem to be quite consistent with observations. We show that by allowing the bubble to heat somewhat nonisotropically, agreement between observed and computed spectral profiles may be obtained, even in the case of helium bubbles at freezing water temperatures. In this case, charge exchange radiation and related processes involving helium atoms and ions become important.


A Systematic Review of Polyvictimization among Children with Attention Deficit Hyperactivity or Autism Spectrum Disorder.
Children with Autism Spectrum Disorder (ASD) or Attention Deficit Hyperactivity Disorder (ADHD) have shown an increased risk for violence and victimization. However, research on exposure to multiple forms of victimization in different contexts are scarce. Hence, the current aim is to review the evidence about polyvictimization among children with ASD or ADHD. PsycInfo, ERIC, ERC, Scopus, and PubMed databases were systematically searched until 12 March 2019 to identify empirical studies with reported prevalence rates of at least four forms of victimization among children with ASD or ADHD. A total of 6/1300 articles were included in the review, ranging in sample sizes from 92 to 4114. The reported prevalence rates for polyvictimization were 1.8% and 23.1% for children with ASD and 7.3% for children with ADHD. The results emphasize the high prevalence of violence and victimization, including polyvictimization, among children with ASD or ADHD. Polyvictimization among children with ASD or ADHD is a highly under researched area. Significant knowledge gaps and important methodological considerations that provide important implications for future research include lack of information on cyber bullying, frequency or intensity of victimization, and the failure to include children as informants and to report health outcomes associated with polyvictimization.


Inter-site generalizability of EEG based age prediction algorithms in the preterm infant.
Objective. To overcome the effects of site differences in EEG-based brain age prediction in preterm infants.Approach. We used a 'bag of features' with a combination function estimated using support vector regression (SVR) and feature selection (filter then wrapper) to predict post-menstrual age (PMA). The SVR was trained on a dataset containing 138 EEG recordings from 37 preterm infants (site 1). A separate set of 36 EEG recordings from 36 preterm infants was used to validate the age predictor (site 2). The feature distributions were compared between sites and a restricted feature set was constructed using only features that were not significantly different between sites. The mean absolute error between predicted age and PMA was used to define the accuracy of prediction and successful validation was defined as no significant differences in error between site 1 (cross-validation) and site 2.Main results. The age predictor based on all features and trained on site 1 was not validated on site 2 (p< 0.001; MAE site 1 = 1.0 weeks,n= 59 versus MAE site 2 = 2.1 weeks,n= 36). The MAE was improved by training on a restricted features set (MAE site 1 = 1.0 weeks,n= 59 versus MAE site 2 = 1.1 weeks,n= 36), resulting in a validated age predictor when applied to site 2 (p= 0.68). The features selected from the restricted feature set when training on site 1 closely aligned with features selected when trained on a combination of data from site 1 and site 2.Significance. The ability of EEG classifiers, such as brain age prediction, to maintain accuracy on data collected at other sites may be challenged by unexpected, site-dependent differences in EEG signals. Permitting a small amount of data leakage between sites improves generalization, leading towards universal methods of EEG interpretation in preterm infants.


Effects of passive hyperthermia versus exercise-induced hyperthermia on immune responses: hormonal implications.
Different stress hormones are released during prolonged exercise and passive hyperthermia. We hypothesized that these different hormonal responses could contribute to the different changes in the immune response during these two challenges. Eight subjects completed three trials in a randomized order. In the control trial (C), the subjects remained in a sitting posture for three hours in thermoneutral conditions. In the exercise hyperthermia trial (E), they exercised for two hours on a treadmill at 65% max in thermoneutral conditions, followed by 1-h recovery in thermoneutral conditions; in the passive hyperthermia trial (PH), the subjects remained in a semi-recumbent position in a climatic chamber for two hours in hot conditions, followed by 1-h recovery in thermoneutral conditions. During the E and PH trials, wind speed and thermal conditions were modulated to reach a rectal temperature (Tre) of 38.5 degrees C at 60 min and 39 degrees C at 120 min. The subjects did not drink during the experiments. Blood samples (10 mL) were taken at 0, 60, 120 and 180 min of each trial. The total white cell count and its subsets were measured; plasma catecholamines, cortisol and prolactin were assayed. In a whole blood assay, blood leukocytes were stimulated by lipopolysaccharide (LPS) or phytohemagglutinin (PHA) for 24 and 48 hours, respectively. Cytokines, such as TNF-alpha, IL-10 and INF-gamma were measured in the culture supernatant. The plasma levels of catecholamines were increased only during E, prolactin was increased only during PH, and cortisol was increased in both E and PH. Only the exercise caused a mobilization of blood leukocytes and leukocyte subsets. The INF-gamma and TNF-alpha production by PHA- and LPS-stimulated blood, respectively, were inhibited in a substantial way in both E and PH compared to control when Tre reached 39 degrees C. Only LPS-induced IL-10 production was enhanced during the exercise. The effects of the challenges were increased with 39 degrees C compared to 38.5 degrees C. Catecholamines play a major role in the mobilization of immunocompetent cells and the production of IL-10 during exercise. Prolactin and catecholamines have adverse role on the immune response, whereas cortisol exerts similar effects during both trials. The consequence could be a protection against inflammatory overshooting.


A prospective study of nosocomial infections in a chronic care facility.
To elucidate the epidemiology of nosocomial infections occurring in nursing homes and chronic care facilities, the authors undertook a prospective study of patients requiring two different levels of nursing care. The overall rate of infection was higher on the intermediate care ward than on the nursing home ward (1.35 versus 0.67 infections/100 patient care days). Pneumonias and symptomatic urinary tract infections accounted for 49 per cent of all infections. Eight of ten cases of pneumonia occurring on the nursing home ward were diagnosed in the winter months, and no case was diagnosed in the summer months. Resistance to gentamicin, tobramycin, ampicillin, and trimethoprim-sulfa was common among organisms causing symptomatic urinary tract infections.


circ_0005379 inhibits the progression of oral squamous cell carcinoma by regulating the miR-17-5p/acyl-CoA oxidase 1 axis.
To investigate the effects of circ_0005379 on the proliferation, apoptosis, migration, and invasion of oral squamous cell carcinoma (OSCC) cells and its mechanism. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression levels of circ_0005379 and miR-17-5p in OSCC tissues and SCC15 cell lines. Western blot was used to detect the expression levels of acyl-CoA oxidase 1 (ACOX1). The circ_0005379 overexpression vector was transfected into SCC15 cells. Methyl thiazolyl tetrazolium blue staining, flow cytometry, Transwell, and Western blot were used to detect the effects of circ_0005379 overexpression on the proliferation, apoptosis, migration, and invasion of SCC15 cells and the expression of E-cadherin, β-catenin, and Snail proteins. Dual luciferase reporter assay and RNA immunoprecipitation were used to examine the regulation of circ_0005379, miR-17-5p, miR-17-5p, and ACOX1 in SCC15 cells. A nude mouse xenograft model of SCC15 cells stably overexpressing circ_0005379 was established, and the effect of circ_0005379 overexpression on the growth of xenografts in nude mice was observed. Compared with adjacent cancer tissues, the expression levels of circ_0005379 and ACOX1 proteins in OSCC tissues were decreased (P<0.05), and the expression level of miR-17-5p was increased (P<0.05). Compared with HOK-16A cells, the expression levels of circ_0005379 and ACOX1 proteins in SCC15 cell lines were decreased (P<0.05), and the expression level of miR-17-5p was increased (P<0.05). After overexpressing circ_0005379, the activity and number of migrating and invading SCC15 cells and the expression levels of β-catenin and Snail proteins were decreased (P<0.05); however, the apoptosis rate and expression level of E-cadherin protein were increased (P<0.05). In SCC15 cells, circ_0005379 targeted the negative regulation of miR-17-5p expression, and miR-17-5p targeted the negative regulation of ACOX1 expression. Overexpressing miR-17-5p or silencing ACOX1 could reverse the effects of circ_0005379 overexpression on the proliferation, apoptosis, migration, and invasion of OSCC cell lines. The tumor volume and weight of nude mice overexpressing circ_0005379 were decreased (P<0.05), the expression levels of circ_0005379 and ACOX1 protein in tumor tissues were increased (P<0.05), and the expression level of miR-17-5p was decreased (P<0.05). circ_0005379 may inhibit the proliferation, migration, and invasion of OSCC cells by downregulating the expression of miR-17-5p and upregulating ACOX1, which promote apoptosis and inhibit tumor growth in vivo. circ_0005379 may be a potential target for OSCC treatment.


[Fatal side-effects of all-trans retinoic acid in the treatment of acute promyelocytic leukemia].
Of 82 patients with acute promyelocytic leukemia (APL) who were treated with all-trans retinoic acid (ATRA), 35 developed leukocytosis and 22 fatal side-effects(15 with retinoic acid syndrome and 7 intracranial bleeding). There was a high mortality in the patient with fatal side-effects. The relationship between leukocytosis and fatal side-effects was analyzed and the effect of therapeutic interventions on the development and prognosis of the fatal side-effects was investigated. The results showed that leukocytosis was a risk factor of the development of fatal side-effects in APL treated with ATRA. ATRA combined with small dose of harringtonin in treating APL can reduce the incidence of intracranial bleeding resulted from leukocytosis and corticosteroid can decrease the mortality of retinoic acid syndrome.


Extracellular superoxide dismutase attenuates lipopolysaccharide-induced neutrophilic inflammation.
Extracellular superoxide dismutase (EC-SOD) is an abundant antioxidant in the lung and vascular walls. Previous studies have shown that EC-SOD attenuates lung injury in a diverse variety of lung injury models. In this study, we examined the role of EC-SOD in mediating lipopolysaccharide (LPS)-induced lung inflammation. We found that LPS-induced neutrophilic lung inflammation was exaggerated in EC-SOD-deficient mice and diminished in mice that overexpressed EC-SOD specifically in the lung. Similar patterns were seen for bronchoalveolar lavage cytokines, such as tumor necrosis factor-alpha, keratinocyte-derived chemokines, and macrophage inflammatory protein-2 as well as expression of lung intercellular adhesion molecule-1, vascular cell adhesion molecule-1, endothelial cell selectin, and platelet selectin. In a macrophage cell line, EC-SOD inhibited LPS-induced macrophage cytokine release, but did not alter expression of intercellular adhesion molecules in endothelial cells. These results suggest that EC-SOD plays an important role in attenuating the inflammatory response in the lung most likely by decreasing release of proinflammatory cytokines from phagocytes.


Bone histomorphometry and vitamin D status after biliopancreatic bypass for obesity.
Bone histomorphometry and vitamin D status were investigated in 41 patients studied 1-5 yr after partial or total biliopancreatic bypass. Metabolic bone disease, characterized by defective mineralization, decreased bone formation rate, and increased surface extent of resorption, was present in 30 patients (73%). Nine patients (22%) were hypocalcemic, but serum 25-hydroxyvitamin D concentrations were normal in all 41 patients. We conclude that metabolic bone disease is common after biliopancreatic bypass and usually occurs in the absence of simple vitamin D deficiency. The pathogenesis of the bone disease is unclear.


Memory Self-Appraisal and Cerebral Glucose Metabolism in Age-Associated Memory Impairment.
The authors used positron emission tomography to measure cerebral glucose metabolism in 43 people with age-associated memory impairment to determine relationships between memory self-appraisal and brain function. People with lower frontal metabolism during a resting state reported more frequent prior mnemonics usage, a measure of memory self-appraisal. A multiple regression analysis indicated that reported mnemonics usage was the most significant predictor of left (P = 0.0004) and right (P = 0.0014) frontal metabolism. These models indicated that mnemonics usage, along with depression ratings, accounted for 39% of left frontal lobe function and, along with visual spatial memory, accounted for 40% of right frontal metabolism. These results suggest that mnemonics usage may compensate for subtle frontal dysfunction or reflect greater efficiency of memory processing.


Comprehensive Analysis of the Immune and Prognostic Implication of TRIM8 in Breast Cancer.
Background: Breast cancer remains one of most lethal illnesses and the most common malignancies among women, making it important to discover novel biomarkers and therapeutic targets for the disease. Immunotherapy has become a promising therapeutic tool for breast cancer. The role of TRIM8 in breast cancer has rarely been reported. Method: Here we identified TRIM8 expression and its potential function on survival in patients with breast cancer using TCGA (The cancer genome atlas), GEO (Gene expression omnibus) database and METABRIC (Molecular Taxonomy of Breast Cancer International Consortium). Then, TIMER and TISIDB databases were used to investigate the correlations between TRIM8 mRNA levels and immune characteristics. Using stepwise cox regression, we established an immune prognostic signature based on five differentially expression immune-related genes (DE-IRGs). Finally, a nomogram, accompanied by a calibration curve was proposed to predict 1-, 3-, and 5-year survival for breast cancer patients. Results: We found that TRIM8 expression was dramatically lower in breast cancer tissues in comparison with normal tissues. Lower TRIM8 expression was related with worse prognosis in breast cancer. TIMER and TISIDB analysis showed that there were strong correlations between TRIM8 expression and immune characteristics. The receiver operating characteristic (ROC) curve confirmed the good performance in survival prediction and showed good accuracy of the immune prognostic signature. We demonstrated the model usefulness of predictions by nomogram and calibration curves. Our findings indicated that TRIM8 might be a potential link between progression and prognosis survival of breast cancer. Conclusion: This is a comprehensive study to reveal that tripartite motif 8 (TRIM8) may serve as a potential prognostic biomarker associating with immune characteristics and provide a novel therapeutic target for the treatment of breast cancer.


The effects of tegaserod on oesophageal function and bolus transport in healthy volunteers: studies using concurrent high-resolution manometry and videofluoroscopy.
Tegaserod is a partial 5-hydroxytryptamine 4 receptor agonist with prokinetic effects on the gastrointestinal tract, its effects on oesophageal function are unknown. A randomized, placebo controlled, double-blind trial assessed the effect of tegaserod on the oesophagus in healthy, asymptomatic subjects. A 7-day course of tegaserod 6 mg b.d. vs. placebo was prescribed (n = 17/21 completed both phases of study). High-resolution manometry and pH measurements were performed before and after a test meal. Bolus transport of liquids and solids was studied by high-resolution manometry and videofluoroscopy. Tegaserod had no effect on lower oesophageal sphincter pressure compared with placebo, peristaltic velocity increased (P < 0.001) and distal contractile pressure decreased slightly (P < 0.05). Transient lower oesophageal sphincter relaxations and reflux were infrequent regardless of treatment. During the studies of bolus transport, high-resolution manometry revealed that tegaserod promoted mid-oesophageal contractility (P < 0.02) and shortened the 'proximal transition zone' (P < 0.05), the level where bolus escape occurred most frequently. These effects had no effect on liquid bolus transport; however a non-significant trend to improved solid bolus transport was observed (66% vs. 31%;P = 0.07). Tegaserod did not alter lower oesophageal sphincter pressure, but had significant effects on peristaltic function. High-resolution manometry promoted mid-oesophageal contractility during bolus transport. This effect was associated with a non-significant trend to improved solid bolus transit.


Intervalence charge transfer luminescence: interplay between anomalous and 5d - 4f emissions in Yb-doped fluorite-type crystals.
In this paper, we report the existence of intervalence charge transfer (IVCT) luminescence in Yb-doped fluorite-type crystals associated with Yb(2+)-Yb(3+) mixed valence pairs. By means of embedded cluster, wave function theory ab initio calculations, we show that the widely studied, very broad band, anomalous emission of Yb(2+)-doped CaF2 and SrF2, usually associated with impurity-trapped excitons, is, rather, an IVCT luminescence associated with Yb(2+)-Yb(3+) mixed valence pairs. The IVCT luminescence is very efficiently excited by a two-photon upconversion mechanism where each photon provokes the same strong 4f(14)-1A1g→ 4f(13)((2)F7/2)5deg-1T1u absorption in the Yb(2+) part of the pair: the first one, from the pair ground state; the second one, from an excited state of the pair whose Yb(3+) moiety is in the higher 4f(13)((2)F5/2) multiplet. The Yb(2+)-Yb(3+) → Yb(3+)-Yb(2+) IVCT emission consists of an Yb(2+) 5deg → Yb(3+) 4f7/2 charge transfer accompanied by a 4f7/2 → 4f5/2 deexcitation within the Yb(2+) 4f(13) subshell: [(2)F5/25deg,(2)F7/2] → [(2)F7/2,4f(14)]. The IVCT vertical transition leaves the oxidized and reduced moieties of the pair after electron transfer very far from their equilibrium structures; this explains the unexpectedly large band width of the emission band and its low peak energy, because the large reorganization energies are subtracted from the normal emission. The IVCT energy diagrams resulting from the quantum mechanical calculations explain the different luminescent properties of Yb-doped CaF2, SrF2, BaF2, and SrCl2: the presence of IVCT luminescence in Yb-doped CaF2 and SrF2; its coexistence with regular 5d-4f emission in SrF2; its absence in BaF2 and SrCl2; the quenching of all emissions in BaF2; and the presence of additional 5d-4f emissions in SrCl2 which are absent in SrF2. They also allow to interpret and reproduce recent experiments on transient photoluminescence enhancement in Yb(2+)-doped CaF2 and SrF2, the appearance of Yb(2+) 4f-5d absorption bands in the excitation spectra of the IR Yb(3+) emission in partly reduced CaF2:Yb(3+) samples, and to identify the broadband observed in the excitation spectrum of the so far called anomalous emission of SrF2:Yb(2+) as an IVCT absorption, which corresponds to an Yb(2+) 4f5/2 → Yb(3+) 4f7/2 electron transfer.


Transfer of clinically relevant gene expression signatures in breast cancer: from Affymetrix microarray to Illumina RNA-Sequencing technology.
Microarrays have revolutionized breast cancer (BC) research by enabling studies of gene expression on a transcriptome-wide scale. Recently, RNA-Sequencing (RNA-Seq) has emerged as an alternative for precise readouts of the transcriptome. To date, no study has compared the ability of the two technologies to quantify clinically relevant individual genes and microarray-derived gene expression signatures (GES) in a set of BC samples encompassing the known molecular BC's subtypes. To accomplish this, the RNA from 57 BCs representing the four main molecular subtypes (triple negative, HER2 positive, luminal A, luminal B), was profiled with Affymetrix HG-U133 Plus 2.0 chips and sequenced using the Illumina HiSeq 2000 platform. The correlations of three clinically relevant BC genes, six molecular subtype classifiers, and a selection of 21 GES were evaluated. 16,097 genes common to the two platforms were retained for downstream analysis. Gene-wise comparison of microarray and RNA-Seq data revealed that 52% had a Spearman's correlation coefficient greater than 0.7 with highly correlated genes displaying significantly higher expression levels. We found excellent correlation between microarray and RNA-Seq for the estrogen receptor (ER; rs = 0.973; 95% CI: 0.971-0.975), progesterone receptor (PgR; rs = 0.95; 0.947-0.954), and human epidermal growth factor receptor 2 (HER2; rs = 0.918; 0.912-0.923), while a few discordances between ER and PgR quantified by immunohistochemistry and RNA-Seq/microarray were observed. All the subtype classifiers evaluated agreed well (Cohen's kappa coefficients >0.8) and all the proliferation-based GES showed excellent Spearman correlations between microarray and RNA-Seq (all rs >0.965). Immune-, stroma- and pathway-based GES showed a lower correlation relative to prognostic signatures (all rs >0.6). To our knowledge, this is the first study to report a systematic comparison of RNA-Seq to microarray for the evaluation of single genes and GES clinically relevant to BC. According to our results, the vast majority of single gene biomarkers and well-established GES can be reliably evaluated using the RNA-Seq technology.


Analysis of subwavelength bandpass plasmonic filters based on single and coupled slot nanocavities.
Subwavelength surface plasmon polariton optical filters based on metal-insulator-metal slot nanocavites are proposed and analyzed by using coupled mode theory and a finite element method. Simulation results reveal that a single slot cavity coupled with two access waveguides possesses a bandpass-filtering characteristic with its performance affected by its geometric parameters. To further improve the filtering performance, we explore coupled slot cavities as high-order plasmonic filters. When the slot cavities are side-coupled, the bandpass filtering spectrum is dependent on the positions of the access waveguides. The two slot cavities can also be set orthogonal, leading to strong mutual coupling. With careful tuning of the relative length between the two cavities, improved filtering spectrum can be obtained. Given the subwavelength footprint of the proposed plasmonic filters, they can be used in an ultradense plasmonic integrated circuit for optical signal processing.


The role of quantitative ultrasound in the assessment of bone: a review.
Quantitative ultrasound (QUS) bone measurement is a promising, relatively new technique for the diagnosis of osteoporosis. Unlike to the more established method of bone densitometry [measurement of bone mineral density (BMD) e.g. using dual X-ray absorptiometry (DEXA)], QUS does not use ionizing radiation. It is cheaper, takes up less space and is easier to use than densitometry techniques. The two QUS parameters currently measured are broadband ultrasound attenuation (BUA) and speed of sound (SOS). The reported age-related changes for healthy women range from -0.27% to -1.62% per year for BUA and from -0.06% to -0.19% per year for SOS. Precision ranges from 1.0 to 3.8% (CV) for BUA and from 0.19 to 0.30% (CV) for SOS. The new method of imaging ultrasound has improved the precision of QUS measurements. QUS is significantly correlated with BMD. Studies with the latest equipment have shown r-values between 0.6 and 0.9 in site-specific measurements, and QUS is thus believed to reflect mainly BMD. However, other studies indicate that QUS measures something other than the actual mineral content of bone, namely bone quality, e.g. in vitro studies have shown that QUS reflects trabecular orientation independently of BMD. In both cross-sectional and prospective studies, QUS seems to be as good a predictor of osteoporotic fractures as BMD. In two large prospective studies, QUS also predicted fracture risk independently of BMD. QUS has just begun to be used systematically for monitoring the response to anti-osteoporotic treatments in prospective trials. In the studies performed, QUS has been found to be useful in the follow-up of patients. QUS is thus a promising new technique for bone assessment.


The Application of FOXO1A Expression Predicts Aggressive Behavior and Poor Prognosis in Gliomas.
Forkhead box, class O, 1A (FOXO1A) is an important factor related to some human malignancies. We tested the association between FOXO1A cytoplasmic expression and World Health Organization grading system in primary brain tumors (PBTs). First of all, Western blot analysis was also performed in normal brain tissue and U87MG, LN229, GBM8401, and U118MG glioma cell lines protein lysates. Then, in order to realize FOXO1A gene expression in gliomas, U87MG, LN229, GBM8401 mRNA were applied to performed quantitative reverse transcription polymerase chain reaction (RT-PCR). At last, the immunohistochemical (IHC) analysis of FOXO1A was performed in 8 non-neoplastic brain tissues and 126 PBTs. The immunostain scores were obtained as the degree of cytoplasmic FOXO1A intensity multiplied by the percentage of positively stained tumor area. On the basis of the results of these in vitro studies, marked increase FOXO1A protein and mRNA expressions in glioma cell lines than in normal human tissue. On the view point of IHC stains, the average immunostain score of FOXO1A in all PBTs was significantly higher than non-neoplastic brain tissues. In addition, the immunostain scores of FOXO1A in high grade were higher than low-grade gliomas. Furthermore, higher cytoplasmic expression of FOXO1A might indicate the shorter overall survival rate in gliomas. Furthermore, FOXO1A expression was associated with isocitrate dehydrogenase I /2, ATRX, and p53 mutation by IHC staining. Therefore, the application of FOXO1A IHC stain might have some benefits to improve diagnostic accuracy, predict tumor progression, and evaluate survival time in glioma patients.


Prevalence of thermophilic Campylobacter spp. in ready-to-eat foods and raw poultry in Northern Ireland.
Although there have been numerous studies investigating the prevalence of campylobacters in animals and raw meats, there are limited data on the persistence of these organisms in ready-to-eat (RTE) foodstuffs. Although poultry is now well established as a major reservoir of thermophilic campylobacters, it is widely assumed that hazard analysis critical control point (HACCP) controls in commercial and industrial settings are effective in eliminating this hazard through thorough cooking of RTE products. Therefore, it was the primary aim of this study to investigate the effectiveness of HACCP controls in eliminating campylobacters in such cooked RTE foods by attempting to isolate viable organisms from product. Concurrently, the results of this study demonstrate that local poultry is highly contaminated with campylobacters. Commercially available RTE foodstuffs (n = 2,030) consisting of 1,061 poultry-related cooked products and 969 other products were analyzed and were not found to contain thermophilic Campylobacter spp. In addition, 107 raw chickens (63 fresh birds and 44 frozen birds) were sampled, and 94% of the fresh birds and 77% of the frozen birds examined were demonstrated to be contaminated with campylobacters, with Campylobacter jejuni, Campylobacter coli, and Campylobacter lari accounting for 69, 30, and 1% of the contaminating organisms, respectively. In general, commercially available RTE foodstuffs, including cooked poultry, are not commonly contaminated with campylobacters and thus do not appear to represent a significant cause of clinical infection of Campylobacter spp. in Northern Ireland. However, raw poultry produce, including fresh and frozen chicken, frequently tested positive for campylobacters. Implementation of HACCP systems by food processors will help to minimize and/or eliminate the risk posed by this organism to the consumer.


[Submucosal lipoma of the colon: abdominal cramps with rectal bleeding and weight loss].
An 81-year-old woman had abdominal cramps, rectal bleeding since 2 weeks and weight loss. Colonoscopy showed an ulcerating tumour of about 4 cm in the transverse colon. Pathological examination of biopsies taken during colonoscopy indicated moderately active chronic colitis. Based on the colonoscopy findings, the tumour appeared to be malignant and laparotomy was performed and the transverse colon was resected. Pathological examination of the resected lesion revealed a submucosal lipoma. The patient recovered fully. Lipomas account for 4% of benign gastrointestinal tumours and 90% of lipomas are submucosal. Their presentation is often similar to malignant tumours. The naked fat sign after biopsy and the elasticity of the lesion are typical features encountered during colonoscopy. Given the high fat content of these lesions, they are easily discernible with CT and MRI. Lipomas with a diameter < 2 cm can be safely removed endoscopically. Larger lesions should be removed by segment resection.


Effect of intravenous pamidronate on bone markers and local bone mineral density in fibrous dysplasia.
Bisphosphonates have proven to be effective in patients with fibrous dysplasia of the bone (FD) as shown by their effect on bone pain, markers of bone turnover, or radiological changes. The aim of this study was to evaluate the usefulness of measuring bone mineral density (BMD) of affected bones to assess the efficacy of bisphosphonate treatment. Seven patients (mean age 26 years) received courses of 180 mg intravenous infusion of pamidronate every 6 months (60 mg/day during 3 days). Clinical symptoms, serum alkaline phosphatase, and urinary C-terminal cross-linking telopeptide of type I collagen were assessed every 3 months. BMD of total skeleton and X-rays of FD areas (FDa) were performed at baseline and at 12 months. BMD of FDa was compared with the contralateral side (CL) using the region of interest program on the total skeleton scan. BMD of total skeleton was normal at baseline. Average BMD of FDa was -11.4% compared with CL, a significantly greater difference than that observed between the left and right sides in healthy controls, -0.7% (P < 0.02). At 12 months bone pain diminished in all patients. Bone turnover markers decreased. Mean total skeleton BMD increased 3.3% (P < 0.02). Subregions of the total skeleton scan presenting FD lesions augmented: arms +9.6% (P < 0.02), legs +4.2%, and pelvis +3.5% (P < 0.05). The increase in mean BMD of FDa was +6.8% compared with +2.6% in CL. No changes were observed on the X-ray. These results indicate that simultaneous determination of markers of bone turnover and BMD of FDa is useful in short-term follow-up to determine the efficacy of intravenous pamidronate.


Surface cooling for rapid induction of mild hypothermia after cardiac arrest: design determines efficacy.
Recently, a novel cooling pad was developed for rapid induction of mild hypothermia after cardiac arrest. The aim of this study was to evaluate the cooling efficacy of three different pad designs for in-hospital cooling. Included in this prospective interventional study were patients with esophageal temperature (Tes) > 34 degrees C on admission. The cooling pad consists of multiple cooling units, filled with a combination of graphite and water, which is precooled to -18 degrees C (design A) or to -9 degrees C (designs B and C) before use. The designs of the cooling pad differed in number, shape, and thickness of the cooling units, with weights of 9.7 kg (design A), 5.3 kg (design B), and 6.2 kg (design C). All three designs were tested in sequential order and were changed according to the results found in the previous trial. Cooling was started after admission until Tes = 34 degrees C, when the cooling pad was removed. The target temperature of Tes = 32-34 degrees C was maintained for 24 hours. Data are presented as medians and interquartile ranges (IQRs = 25%-75%) or proportions. Cooling rates were 3.4 degrees C/hour (IQR = 2.5-3.7) with design A (n = 12), 2.8 degrees C/hour (IQR = 1.6-3.3) with design B (n = 7), and 2.9 degrees C/hour (IQR = 1.9-3.6) with design C (n = 10; p = 0.5). To reach 34 degrees C, the cooling pad had to be exchanged with a new one due to melting and therefore depleting cooling capacity in three patients with design A, in five patients with design B, and in no patient with design C (p = 0.004). With adequate design and storage temperature, the cooling pad proved to be efficient for rapid in-hospital cooling of patients resuscitated from cardiac arrest.


Contradicting habitat type-extinction risk relationships between living and fossil amphibians.
Trait analysis has become a crucial tool for assessing the extinction risk of species. While some extinction risk-trait relationships have been often identical between different living taxa, a temporal comparison of fossil taxa with related current taxa was rarely considered. However, we argue that it is important to know if extinction risk-trait relations are constant or changing over time. Herein we investigated the influence of habitat type on the persistence length of amphibian species. Living amphibians are regarded as the most threatened group of terrestrial vertebrates and thus of high interest to conservationists. Species from different habitat types show differences in extinction risk, i.e. species depending on flowing waters being more threatened than those breeding in stagnant sites. After assessing the quality of the available amphibian fossil data, we show that today's habitat type-extinction risk relationship is reversed compared to fossil amphibians, former taxa persisting longer when living in rivers and streams, thus suggesting a change of effect direction of this trait. Neither differences between amphibian orders nor environmentally caused preservation effects could explain this pattern. We argue this change to be most likely a result of anthropogenic influence, which turned a once favourable strategy into a disadvantage.


All low voltage lateral junction scanning tunneling microscope with very high precision and stability.
We describe the first lateral junction and fully low voltage scanning tunneling microscope, featuring very high precision, stability, compactness, and image quality (highly oriented pyrolytic graphite atomic resolution images). In its core, the tip and sample each sit on one of two parallel-mounted piezoelectric tube scanners so that the tip-sample gap is regulated along the scanners' pairing direction. The scanner's large lateral deflection provides a large gap regulation range even under low voltages, allowing exclusively using only low voltage (less than +/-15 V) operational amplifiers to precisely implement the coarse (inertial slider) and fine approach, feedback control, and hence the entire electronics. Because the scanners are identical and adjacent, thermal drifts are minimal.


Cost of Dengue Vector Control Activities in Malaysia.
Dengue fever, an arbovirus disease transmitted by Aedes mosquitoes, has recently spread rapidly, especially in the tropical countries of the Americas and Asia-Pacific regions. It is endemic in Malaysia, with an annual average of 37,937 reported dengue cases from 2007 to 2012. This study measured the overall economic impact of dengue in Malaysia, and estimated the costs of dengue prevention. In 2010, Malaysia spent US$73.5 million or 0.03% of the country's GDP on its National Dengue Vector Control Program. This spending represented US$1,591 per reported dengue case and US$2.68 per capita population. Most (92.2%) of this spending occurred in districts, primarily for fogging. A previous paper estimated the annual cost of dengue illness in the country at US$102.2 million. Thus, the inclusion of preventive activities increases the substantial estimated cost of dengue to US$175.7 million, or 72% above illness costs alone. If innovative technologies for dengue vector control prove efficacious, and a dengue vaccine was introduced, substantial existing spending could be rechanneled to fund them.


A Combination Analysis of IVIM-DWI Biomarkers and T2WI-Based Texture Features for Tumor Differentiation Grade of Cervical Squamous Cell Carcinoma.
To explore the value of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and texture analysis on T2-weighted imaging (T2WI) for evaluating pathological differentiation of cervical squamous cell carcinoma. This retrospective study included a total of 138 patients with pathologically confirmed poor/moderate/well-differentiated (71/49/18) who underwent conventional MRI and IVIM-DWI scans. The values of ADC, D, D ∗ , and f and 58 T2WI-based texture features (18 histogram features, 24 gray-level co-occurrence matrix features, and 16 gray-level run length matrix features) were obtained. Multiple comparison, correlation, and regression analyses were used. For IVIM-DWI, the ADC, D, D ∗ , and f were significantly different among the three groups (p < 0.05). ADC, D, and D ∗ were positively correlated with pathological differentiation (r = 0.262, 0.401, 0.401; p < 0.05), while the correlation was negative for f (r = -0.221; p < 0.05). The comparison of 52 parameters of texture analysis on T2WI reached statistically significant levels (p < 0.05). Multivariate logistic regression analysis incorporated significant IVIM-DWI, and texture features on T2WI showed good diagnostic performance both in the four differentiation groups (poorly vs. moderately, area under the curve(AUC) = 0.797; moderately vs. well, AUC = 0.954; poorly vs. moderately and well, AUC = 0.795; and well vs. moderately and poorly, AUC = 0.952). The AUCs of each parameters alone were smaller than that of each regression model (0.503∼0.684, 0.547∼0.805, 0.511∼0.712, and 0.636∼0.792, respectively; pairwise comparison of ROC curves between regression model and individual variables, p < 0.05). IVIM-DWI biomarkers and T2WI-based texture features had potential to evaluate the pathological differentiation of cervical squamous cell carcinoma. The combination of IVIM-DWI with texture analysis improved the predictive performance.


Structured Set Intra Prediction With Discriminative Learning in a Max-Margin Markov Network for High Efficiency Video Coding.
This paper proposes a novel model on intra coding for High Efficiency Video Coding (HEVC), which simultaneously predicts blocks of pixels with optimal rate distortion. It utilizes the spatial statistical correlation for the optimal prediction based on 2-D contexts, in addition to formulating the data-driven structural interdependences to make the prediction error coherent with the probability distribution, which is desirable for successful transform and coding. The structured set prediction model incorporates a max-margin Markov network (M3N) to regulate and optimize multiple block predictions. The model parameters are learned by discriminating the actual pixel value from other possible estimates to maximize the margin (i.e., decision boundary bandwidth). Compared to existing methods that focus on minimizing prediction error, the M3N-based model adaptively maintains the coherence for a set of predictions. Specifically, the proposed model concurrently optimizes a set of predictions by associating the loss for individual blocks to the joint distribution of succeeding discrete cosine transform coefficients. When the sample size grows, the prediction error is asymptotically upper bounded by the training error under the decomposable loss function. As an internal step, we optimize the underlying Markov network structure to find states that achieve the maximal energy using expectation propagation. For validation, we integrate the proposed model into HEVC for optimal mode selection on rate-distortion optimization. The proposed prediction model obtains up to 2.85% bit rate reduction and achieves better visual quality in comparison to the HEVC intra coding.


Ultrasonography as a tool in predicting the severity of dengue fever in children--a useful aid in a developing country.
Dengue fever accounts for significant mortality in developing countries. Dengue fever serology takes a week at least to be reported positive, thus necessitating the need for other markers of diagnosis and prognosis. The purpose of this study was to investigate the role of ultrasonography as a tool in diagnosing and predicting the severity of dengue fever in children. This was a prospective study conducted in a tertiary pediatric centre from September 2010 to July 2012. Three hundred twenty-four children with confirmed dengue fever were compared with 422 children of suspected dengue fever. Severity of illness was graded as per WHO criteria and sonography findings were correlated to the grade of illness. Gallbladder wall thickening was seen in 75% of the children with confirmed dengue fever. A significant difference was seen between survivors and non-survivors with respect to pericholecystic fluid collection (P = 0.002), hepatic intraparenchymal fluid (P < 0.001), splenomegaly (P = 0.002), splenic subcapsular fluid (P < 0.001), peripancreatic fluid (P < 0.001), perirenal fluid (P < 0.001) and pericardial fluid (P < 0.001). Other findings included ascites, pleural effusion, hepatomegaly and splenomegaly, which were present irrespective of grade of illness. Ultrasonography can be used as a useful tool in developing countries to predict the severity of dengue fever in children.


[Mitochondrial Antioxidant Plastomitin Improves Cardiac Function in Doxorubicin-Induced Cardiomyopathy].
The aim of the study was to ascertain whether the use of plastomitin, the mitochondrial antioxidant, can affect the development of systolic dysfunction that occurs in rats after 4 weeks of doxorubicin treatment (2 mg/kg weekly). Materials and methods. Male Wistar rats weighing 320-380 g were used in this work. Echocardiographic study was carried out using Vevo 1100 with linear probe 13-24 MHz frequency. Results. Echocardiographic study of rats through 8 weeks from the beginning of doxorubicin treatment showed the presence of systolic dysfunction with decrease of ejection fraction of the left ventricle (LV) by 32%. Hearts of rats, to which plastomitin (0.32 mg/kg daily) was administered simultaneously with doxorubicin, showed significantly increased ejection fraction and shortening fraction as compared with doxorubicin group, and these values were close to the control. In experiments with simultaneous registration of LV pressure and volume, it was found that the hearts of all rats treated with doxorubicin showed reduced contractility index and stroke work, while maintaining normal cardiac output. Such compensation in experiments with treatment with doxorubicin alone was achieved through significant reduction in the peripheral resistance, slowing of myocardial relaxation, and facilitation of LV diastolic filling during prolonged diastolic pause (the heart rate was slowed by 23%). In experiments with simultaneous application of doxorubicin and plastomitin, the compensation was achieved through preservation of myocardial contractility and relaxability, the heart rate and peripheral resistance. This method of compensation is more beneficial for the body, because it does not restrict the supply of organs and tissues with oxygen, and has significant advantage over doxorubicin group at equal heart rate. Conclusion. The results allow to conclude that the use of plastomitin together with doxorubicin prevents the development of doxorubicin-induced systolic dysfunction.


To deliberate or not? The role of intuition and deliberation when controlling for irrelevant information in selection decisions.
In selection decisions, decision makers often struggle to ignore irrelevant information, such as candidates' age, gender and attractiveness, which can lead to suboptimal decisions. One way to correct the effects of these irrelevant attributes is to consider them as suppressor variables, and penalize individuals who unjustifiably benefit from them. Previous research demonstrated that people have difficulties doing so. In five experiments (N = 1325), we examined the mechanism at the core of people's ability to do so. We found that triggering System 2 did not improve participants' ability to correct for this bias. The majority of those who were successful did so even when denied the opportunity to deliberate. We suggest that logic intuition-not deliberation-is the basis for successfully considering irrelevant information as suppressors. Our results are in line with a revised dual-process approach, in which solving reasoning problems can occur directly through System 1 and does not require an override by a System 2's-based process.


Synthetic high-energy computed tomography image via a Wasserstein generative adversarial network with the convolutional block attention module.
Computed tomography (CT) is now universally applied into clinical practice with its non-invasive quality and reliability for lesion detection, which highly improves the diagnostic accuracy of patients with systemic diseases. Although low-dose CT reduces X-ray radiation dose and harm to the human body, it inevitably produces noise and artifacts that are detrimental to information acquisition and medical diagnosis for CT images. This paper proposes a Wasserstein generative adversarial network (WGAN) with a convolutional block attention module (CBAM) to realize a method of directly synthesizing high-energy CT (HECT) images through low-energy scanning, which greatly reduces X-ray radiation from high-energy scanning. Specifically, our proposed generator structure in WGAN consists of Visual Geometry Group Network (Vgg16), 9 residual blocks, upsampling and CBAM, a subsequent attention block. The convolutional block attention module is integrated into the generator for improving the denoising ability of the network as verified by our ablation comparison experiments. Experimental results of the generator attention module ablation comparison indicate an optimization boost to the overall generator model, obtaining the synthesized high-energy CT with the best metric and denoising effect. In different methods comparison experiments, it can be clearly observed that our proposed method is superior in the peak signal-to-noise ratio (PSNR), structural similarity index measure (SSIM) and most of the statistics (average CT value and its standard deviation) compared to other methods. Because P<0.05, the samples are significantly different. The data distribution at the pixel level between the images synthesized by the method in this paper and the high-energy CT images is also most similar. Experimental results indicate that CBAM is able to suppress the noise and artifacts effectively and suggest that the image synthesized by the proposed method is closest to the high-energy CT image in terms of visual perception and objective evaluation metrics.


Metformin improves cardiac functional recovery after ischemia in rats.
The biguanide, metformin, is widely used for the treatment of type 2 diabetes mellitus. In the recently published United Kingdom Prospective Diabetes Study (UKPDS), it was shown that the use of metformin was associated with a reduction of macrovascular complications compared to other blood glucose-lowering strategies. The present study was aimed at determining whether metformin has direct beneficial effects on the heart. We tested the effects of metformin on cardiac functional recovery after a mild ischemic incident (stunning) in our isolated, erythrocyte perfused, rat working-heart model. Three groups were tested: vehicle, 50 and 500 micromol/l metformin (total n = 6). In diabetic rats, a concentration of 50 microM has been shown to reduce the blood glucose concentration. Slight metformin-induced increases in coronary blood flow during normoxia (pre-ischemically) and during reperfusion (post-ischemically) were observed and compared to vehicle (p < 0.05). Both metformin concentrations significantly reduced cardiac functional loss induced by the 12-min global ischemic incident compared with vehicle (3.4 +/- 1.0 % and 3.5 +/- 0.6 % loss during metformin versus 10.7 +/- 0.8 % during vehicle, p < 0.001). This study clearly shows that metformin acutely improves cardiac function after a mild ischemic incident (stunning) in rats.