Salivary analytes in patients with oral squamous cell carcinoma.
Literature data indicates that measurement of certain salivary constituents might serve as a useful diagnostic/prognostic tool in the patients with oral squamous cell carcinoma (OSCC). In 24 patients with OSCC (60 +/- 2.5 yrs) and in 24 controls (24 +/- 3.7 yrs) we have determined levels of salivary magnesium, calcium, copper, chloride, phosphate, potassium, sodium, total proteins and amylase. Sodium, potassium and chloride were determined by indirect potentiometry whereas copper, magnesium and phosphate were determined by atomic absorption spectrophotometry. Total proteins were determined by pyrogalol colorimetric method. Amylase levels were determined by continued colorimetric method. Statistical analysis was performed by use of chi2 test and Spearman's correlation test. The results of this study indicate that the concentrations of sodium and chloride were significantly elevated in patients with OSCC when compared to the controls. However, level of total protein was significantly decreased when compared to the healthy controls. Furthermore, there was a negative correlation between alcohol consumption and total protein concentration in patients with oral carcinoma. We might conclude that in patients with OSCC increased salivary sodium and chloride might reflect their overall dehydration status due to alcohol consumption rather than consequence of OSCC itself.


[Critical considerations on the behavior of immunoglobulins in rheumatoid arthritis].
Critical evaluation of immunoglobulins in Rheumatoid Arthritis. It has been studied the behavior of the serum and synovial immunoglobulins of 62 patients afftected arthritis reheumatoid in various clinic stages; the valued have been expressed in mg% and mg/g of proteins. The serum levels of the IgG and IgA are higher in the cases of R.A. than in normals. The synovial concentrations of the IgA and IgM are lower than the respective serum values, while the phenomenon is less evident for the IgG probably because the last are synthetised in the synovial means. It exists, however, a interdipendence between the concentration of the serum and synovial immunoglobulins. The concentrations of the immunoglobulines, both serum and synovial, are not in relation with the most usual humoral phlogosis-tests, as well as they are not correlable with the values of the naturals antiproteases and with some fractions of the complement (both of the classic and alternative pathway). The variations of the immunoglobulins are, in the R.A., aspecific and of different intensity therefore their determination is not proposable neither as test of measure of the phlogosis nor as index of disease.


Pulmonary complications following tricyclic antidepressant overdose in an adolescent.
To report a case of pulmonary edema following a tricyclic antidepressant (TCA) overdose in an adolescent. A 14-year-old girl with a history of prior suicide attempts ingested 54 50-mg desipramine hydrochloride tablets (45 mg/kg ingestion). The patient developed a cardiac dysrhythmia and hypotension, which were successfully treated. She subsequently developed pulmonary edema and a clinical picture suggestive of adult respiratory distress syndrome (ARDS). She was successfully managed with fluid restriction, tracheal intubation, application of positive end-expiratory pressure (PEEP), and vasopressors. The patient was discharged without any clinical sequelae. Pulmonary complications secondary to TCA overdose have rarely been reported in children. We reviewed literature pertaining to the etiology, epidemiology, pathophysiology, and management of TCA-induced lung injury, as well as other case reports. We discuss the potential relationship between sequelae resulting from TCA ingestion (e.g., cardiac disturbances, hypotension, acidosis, gastric aspiration, pneumonia) and the development of ARDS and pulmonary edema, and relate this association to our patient. Pulmonary edema and a clinical picture suggestive of ARDS was noted in an adolescent girl who ingested a large quantity of desipramine. Her lung injury may have been the result of a variety of factors including hypotension, metabolic acidosis, possible aspiration, or a direct action on the lung parenchyma by desipramine. We attribute her favorable clinical outcome to early intervention consisting of tracheal intubation, PEEP, fluid restriction, and vasopressor therapy.


Johann Joseph on Geometrical-Optical Illusions: A Translation and Commentary.
The term geometrical-optical illusions was coined by Johann Joseph Oppel (1815-1894) in 1855 in order to distinguish spatial distortions of size and orientation from the broader illusions of the senses. We present a translation of Oppel's article and a commentary on the material described in it. Oppel did much more than give a name to a class of visual spatial distortions. He examined a variety of figures and phenomena that were precursors of later, named illusions, and attempted to quantify and interpret them.


Expression of Vascular Endothelial Growth Factor Receptors in Benign Vascular Lesions of the Orbit: A Case Series.
Vascular lesions of the orbit, although not malignant, can cause morbidity because of their location near critical structures in the orbit. For the same reason, they can be challenging to remove surgically. Anti-vascular endothelial growth factor (VEGF) drugs are increasingly being used to treat diseases with prominent angiogenesis. Our study aimed to determine to what extent VEGF receptors and their subtypes are expressed on selected vascular lesions of the orbit. Retrospective case series of all orbital vascular lesions removed by one of the authors (JAG) at the Mayo Clinic. A total of 52 patients who underwent removal of vascular orbital lesions. The pathology specimens from the patients were retrieved, their pathologic diagnosis was confirmed, demographic and clinical information were gathered, and sections from vascular tumors were stained with vascular endothelial growth factor receptor (VEGFR), vascular endothelial growth factor receptor type 1 (VEGFR1), vascular endothelial growth factor receptor type 2 (VEGFR2), and vascular endothelial growth factor receptor type 3 (VEGFR3). The existence and pattern of staining with VEGF and its subtypes on these lesions. There were 28 specimens of venous malformations, 4 capillary hemangiomas, 7 lymphatic malformations, and 6 lymphaticovenous malformations. All samples stained with VEGF, 55% stained with VEGFR1, 98% stained with VEGFR2, and 96% stained with VEGFR3. Most (94%) of the VEGFR2 staining was diffuse. Most orbital vascular lesions express VEGF receptors, which may suggest a future target for nonsurgical treatment.


Longitudinal coordination of motor output during swimming in Xenopus embryos.
Little is known about the neural mechanisms that control the phenomenon of rostro-caudal delay. In Xenopus embryos there is a constant rostro-caudal delay of 2-5 ms mm-1 during fictive swimming. Rostro-caudal delay is not significantly correlated with cycle period. When NMDA is applied to the caudal spinal cord there is a decrease and in some cases a reversal in rostro-caudal delay. Conversely applying excitatory antagonists to the caudal spinal cord leads to an increase in delay. When caudal mid-cycle inhibition is reduced either pharmacologically using strychnine or surgically through hemisection of the spinal cord, there is an increase in rostro-caudal delay. Rostro-caudal delays are too small to be explainable on the basis of axonal conduction velocities and synaptic delays. This suggests that the central pattern generator of Xenopus behaves as a series of coupled oscillators and that the nature of the coupling, together with a longitudinal gradient in excitability associated with the oscillators, contributes to the observed rostro-caudal delay.


Targeting Jurkat T Lymphocyte Leukemia Cells by an Engineered Interferon-Alpha Hybrid Molecule.
Adult T-cell leukemia/lymphoma (ATL) is a very aggressive T cell malignancy that carries a poor prognosis, primarily due to its resistance to chemotherapy and to life-threatening infectious complications. Interferon-alpha (IFNα) has been used in combination with the anti-retroviral drug zidovudine to treat patients with ATL. However, the efficacy of long-term therapy is significantly limited due to the systemic toxicity of IFNα. We utilized phage display library screening to identify short peptides that specifically bind to Jurkat T lymphocyte leukemia cells. By fusing the Jurkat-binding peptide to the C-terminus of IFNα, we constructed an engineered chimeric IFNα molecule (IFNP) for the treatment of ATL. We found that IFNP exhibited significantly higher activity than wild type IFNα in inhibiting the growth of leukemia cells and inducing cell blockage at the G0/G1 phase. The synthetic IFNP molecule exerted its antitumor activity by upregulating the downstream genes involved in the STAT1 pathway and in apoptosis. Using a cell receptor binding assay, we showed that this Jurkat-binding peptide facilitated the binding affinity of IFNα to the cell surface type I IFN receptor. The isolated Jurkat-binding peptide significantly potentiates the therapeutic activity of IFNα in T lymphocyte leukemia cells. The engineered IFNP molecule may prove to a novel antitumor approach in the treatment of patients with ATL.


A retrospective comparison of cervical intervertebral disk disease in nonchondrodystrophic large dogs versus small dogs.
Medical records of 144 small-breed dogs (< or =15 kg) and 46 medium- to large-breed dogs (>15 kg) with surgically confirmed, Hansen type I, cervical intervertebral disk extrusions were reviewed. The most common clinical presentation was cervical hyperesthesia. The most common sites affected were the second (C(2)) to third (C(3)) cervical intervertebral disk space in small-breed dogs and the sixth (C(6)) to seventh (C(7)) cervical intervertebral disk space in the larger dogs. Following surgery, 99% of the dogs had resolution of cervical hyperesthesia and were able to ambulate unassisted. Seven (4%) dogs required a second surgery; four of these were large-breed dogs.


Super-Bulky Penta-arylcyclopentadienyl Ligands: Isolation of the Full Range of Half-Sandwich Heavy Alkaline-Earth Metal Hydrides.
Hydrogenolysis of the half-sandwich penta-arylcyclopentadienyl-supported heavy alkaline-earth-metal alkyl complexes (CpAr )Ae[CH(SiMe3 )2 ](S) (CpAr =C5 Ar5 , Ar=3,5-i Pr2 -C6 H3; S=THF or DABCO) in hexane afforded the calcium, strontium, and barium metal-hydride complexes as the same dimers [(CpAr )Ae(μ-H)(S)]2 (Ae=Ca, S=THF, 2-Ca; Ae=Sr, Ba, S=DABCO, 4-Ae), which were characterized by NMR spectroscopy and single-crystal X-ray analysis. 2-Ca, 4-Sr, and 4-Ba catalyzed alkene hydrogenation under mild conditions (30 °C, 6 atm, 5 mol % cat.), with the activity increasing with the metal size. A variety of activated alkenes including tri- and tetra-substituted olefins, semi-activated alkene (Me3 SiCH=CH2 ), and unactivated terminal alkene (1-hexene) were evaluated.


Malaria Host Candidate Genes Validated by Association With Current, Recent, and Historical Measures of Transmission Intensity.
Human malaria susceptibility is determined by multiple genetic factors. It is unclear, however, which genetic variants remain important over time. Genetic associations of 175 high-quality polymorphisms within several malaria candidate genes were examined in a sample of 8096 individuals from northeast Tanzania using altitude, seroconversion rates, and parasite rates as proxies of historical, recent, and current malaria transmission intensity. A principal component analysis was used to derive 2 alternative measures of overall malaria propensity of a location across different time scales. Common red blood cell polymorphisms (ie, hemoglobin S, glucose-6-phosphate dehydrogenase, and α-thalassemia) were the only ones to be associated with all 3 measures of transmission intensity and the first principal component. Moderate associations were found between some immune response genes (ie, IL3 and IL13) and parasite rates, but these could not be reproduced using the alternative measures of malaria propensity. We have demonstrated the potential of using altitude and seroconversion rate as measures of malaria transmission capturing medium- to long-term time scales to detect genetic associations that are likely to persist over time. These measures also have the advantage of minimizing the deleterious effects of random factors affecting parasite rates on the respective association signals.


Role of a transcription factor (CREB) in memory processes.
Memory storage includes a short-term phase (STM) which requires the phosphorylation of pre-existing proteins, and a long-term phase (LTM) which needs the novel synthesis of RNA and proteins. Cyclic AMP and a specific transcription factor (cAMP response element binding protein or CREB) play a central role in the formation of LTM in aplysia, drosophila and mice. Following its phosphorylation by protein kinase A, CREB binds to the enhancer element CRE which is located in the upstream region of cAMP-responsive genes, thus triggering transcription. Some of the newly-synthesized proteins are additional transcription factors that ultimately give rise to the activation of late response genes, whose products are responsible for the modification of synaptic efficacy leading to LTM. In aplysia, CREB activation has been interfered with by microinjection of CRE containing oligonucleotides into cultured neurons. Under these conditions LTM is blocked while STM remains unchanged. In drosophila, CREB function has been disrupted using a reverse genetic approach. Thus, LTM has been specifically blocked by the induced expression of a CREB repressor isoform, and enhanced by the induced expression of an activator isoform. In mouse, the role of CREB has been confirmed by behavioural analyses of a knock-out line with a targeted mutation in the CREB gene. In these mutants, learning and STM are normal, whereas LTM is disrupted. On the whole, the data suggest that encoding of long term memories involve highly conserved molecular mechanisms.


IL-1β mediates lung neutrophilia and IL-33 expression in a mouse model of viral-induced asthma exacerbation.
Viral-induced asthma exacerbations, which exhibit both Th1-type neutrophilia and Th2-type inflammation, associate with secretion of Interleukin (IL)-1β. IL-1β induces neutrophilic inflammation. It may also increase Th2-type cytokine expression. We hypothesised that IL-1β is causally involved in both Th1 and Th2 features of asthma exacerbations. This hypothesis is tested in our mouse model of viral stimulus-induced asthma exacerbation. Wild-type (WT) and IL-1β deficient (IL-1β-/-) mice received house dust mite (HDM) or saline intranasally during three weeks followed by intranasal dsRNA (PolyI:C molecule known for its rhinovirus infection mimic) for three consecutive days to provoke exacerbation. Bronchoalveolar lavage fluid was analysed for inflammatory cells and total protein. Lung tissues were stained for neutrophilic inflammation and IL-33. Tissue homogenates were analysed for mRNA expression of Muc5ac, CXCL1/KC, TNF-α, CCL5, IL-25, TSLP, IL-33, IL-1β, CCL11 and CCL2 using RT-qPCR. Expression of IL-1β, neutrophil chemoattractants, CXCL1 and CCL5, the Th2-upstream cytokine IL-33, and Muc5ac were induced at exacerbation in WT mice and were significantly inhibited in IL-1β-/- mice at exacerbation. Effects of HDM alone were not reduced in IL-1β-deficient mice. Without being involved in the baseline HDM-induced allergic asthma, IL-1β signalling was required to induce neutrophil chemotactic factors, IL-33, and Muc5ac expression at viral stimulus-induced exacerbation. We suggest that IL-1β has a role both in neutrophilic and Th2 inflammation at viral-induced asthma exacerbations.


The treatment of cervical pregnancy with high-intensity focused ultrasound followed by suction curettage: report of three cases.
Cervical pregnancy (CP) is a rare type of ectopic pregnancy and is considered to be a life-threatening condition due to the risk of severe hemorrhage. Unfortunately, no consensus on standard conservative treatment for CP has been established. The study objective was to evaluate the efficacy and safety of high-intensity focused ultrasound (HIFU) followed by suction curettage for cervical pregnancy. Three patients with cervical pregnancy undergoing high-intensity focused ultrasound followed by suction curettage were analyzed. Patient age, gestational age, endocervical mass, serum human chorionic gonadotrophin (HCG) level, blood loss, and time for normal menstruation recovery were recorded. Three patients with cervical pregnancy were successfully treated with HIFU followed by suction curettage. After HIFU treatment, the fetal cardiac activity disappeared or the blood flow in the pregnancy tissue significantly decreased. The termination of the cervical pregnancy of all three patients was performed successfully without heavy bleeding. The estimated blood loss was 10-20 ml. The time for menstruation recovery was 30-45 days. No obvious complications of HIFU were observed in these cases. High-intensity focused ultrasound followed by suction curettage seems to be considered as conservative management for patients who desire to preserve their uterus.


Wetting Transition of Condensed Droplets on Nanostructured Superhydrophobic Surfaces: Coordination of Surface Properties and Condensing Conditions.
Nanostructured superhydrophobic surfaces have been actively explored to promote favorable droplet dynamics for a wide range of technological applications. However, the tendency of condensed droplets to form as pinned states greatly limits their applicability in enhancing condensation heat transfer efficiency. Despite recent progresses, the understanding of physical mechanisms governing the wetting transition of condensed droplets is still lacking. In this work, a nanostructured superhydrophobic surface with tapered nanogaps is fabricated to demonstrate the coordination of surface wetting property, topography, and the condensing condition on the wetting state and dynamic behavior of condensed droplets. Combining the environmental scanning electron microscopy and optical visualization methods, we systematically show the morphology of nucleated droplets in nanostructures and the droplet dynamic evolution throughout the growth stages, which provides the direct evidence of condensing condition-induced droplet wetting transition. When the surface subcooling is smaller than 0.3 K, the droplets formed as the Cassie-Baxter state, followed by coalescence-induced droplet jumping. With the increase of surface subcooling up to 0.6 K, however, droplet formation occurs randomly inside nanogaps, resulting in the loss of superhydrophobicity. These new observations along with the new insights about the coordination of surface properties and condensing conditions on droplet wetting transition are useful for guiding the development of novel surfaces for improving droplet removal and phase-change heat transfer.


Comparison of Collagen Cross-Linking and Amniotic Membrane Transplantation in an Experimental Alkali Burn Rabbit Model.
To compare the effects of collagen cross-linking (CXL) and amniotic membrane transplantation (AMT) on acute corneal alkali burns. After establishment of an alkali burn model, 32 rabbits were divided into 4 groups: control group, AMT group, CXL group, and AMT + CXL (combined) group. Clinical parameters, including epithelial wound, opacity, ulceration, and neovascularization, were evaluated on postinjury days 1, 7, 14, and 18. Histological parameters were examined in hematoxylin/eosin (H&E) and Masson trichrome-stained corneal sections. Immunohistochemical analyses, including a terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate nick-end labeling assay and cluster of differentiation 68 (CD68) labeling, were performed to determine the apoptotic index and macrophage activation. On postinjury day 18, the epithelial wound of AMT {4.08% [interquartile range (IQR), 0.68%-5.22%]}, CXL [1.84% (IQR, 0.01%-3.89%)], and combined [3.44% (IQR, 0.01%-4.36%)] groups were significantly lower than the control [15.23% (IQR, 9.86%-23.06%)] group (P = 0.003). No significant difference was detected between the groups in terms of opacity (P = 0.303). Neovascularization was the least severe in the CXL group [16.18% (IQR, 8.39%-21.28%)] and the most severe in the AMT [34.47% (IQR, 17.71%-62.77%)] and combined [35.12% (IQR, 31.96%-59.98%)] groups on day 18 (P = 0.033). Significant increases in the apoptotic index and CD68 labeling were detected in the CXL and combined groups compared with those in the control group (P = 0.047 and P = 0.001, respectively). CXL treatment is an effective adjuvant treatment for promoting reepithelialization, reducing inflammation and neovascularization, and preventing ulceration in acute alkali burns. Providing AMT after suppressing inflammation may be a more effective treatment.


Coherent interactions in femtosecond transient grating.
Transient grating of a dye in liquid has been measured as a function of the electronic coherence period. A diffractive beam splitter and a pair of wedge prisms are implemented to achieve precise spatial phase overlap and interferometrically accurate control of the time delay between the pump pulses. As the electronic coherence period is varied, coherent interactions lead to an enhancement or loss of the sharp feature in the transient grating signal near time zero, which is usually called coherent spike. Sensitivity of the transient grating signal to the solvation process also changes by the coherence time delay. All the features can be accounted for by invoking third-order nonlinear response functions. Numerical simulations have been performed to corroborate our description. This work identifies a major source of the coherent spike in the transient grating and transient absorption experiments. In addition, it allows us to propose a method that measures the solvation function more efficiently than conventional transient grating technique does.


In situ crystallization of low-melting ionic liquid [BMIM][PF6] under high pressure up to 2 GPa.
To develop a new practical method of purifying and recycling ionic liquids, we performed direct microscopic observations and in situ crystallization of low-melting ionic liquid, 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF(6)]), in detail by high pressure Raman spectroscopy. Compression of [BMIM][PF(6)] was measured under pressures up to about 2.0 GPa at temperatures 293-353 K by using a high pressure diamond anvil cell (DAC). At room temperature, with pressure increasing, the characteristic bands of [BMIM][PF(6)] displayed nonmonotonic pressure-induced frequency shifts, and [BMIM][PF(6)] experienced the liquid-solid phase transition at about 0.50 GPa. In separate experiments, in situ crystallization of low-melting ionic liquid [BMIM][PF(6)] were also measured at various P-T regions, in order to improve the understanding of its stability limits. Finally, the T versus P phase diagram of [BMIM][PF(6)] was constructed, and it showed that the melting point was an increase function of pressure. It was also indicated that the structure changes in the crystalline and liquid states under high pressure might also be associated with conformational changes in the butyl chain. Pressure-released Raman spectra also showed that the phase transition of [BMIM][PF(6)] was reversible.


Ultrasonic scattering properties of three random media with implications for tissue characterization.
Random media with different structural properties were used to simulate some of the differences in liver morphology that may occur with disease. First, a reference medium consisting of glass spheres in agar was studied to verify the accuracy and precision of the data obtained with our equipment and processing procedures. Then, studies were conducted on a pair of media comprised of graphite particles in gelatin, one of the pair with twice as many particles as the other. Finally, studies were carried out on a set of media composed of Sephadex particles in water. Three samples were employed, each with a different size of Sephadex. The average differential scattering cross section per unit volume sigma sd (v) of each media was obtained as a function of scattering angle v and frequency. The measured sigma sd were compared with predictions based on models of scattering from the media. The agreement between the measured and predicted sigma sd of the glass sphere medium was excellent. The graphite medium with twice the number of particles as the other was observed to scatter twice as much power as the other. The shape of the angular scattering pattern measured from each size of Sephadex followed the prediction reasonably well. The largest size exhibited marked variations in the shape of sigma sd as a function of frequency, while the absolute magnitude of sigma sd of the smallest size grade was extremely sensitive to frequency. Our results suggest that the dependence of sigma sd (v) on scatterer number density and size, both in absolute magnitude and shape, can provide reliable information which may be useful in the diagnosis of some diseases.


Cystathionine β-synthase mediated PRRX2/IL-6/STAT3 inactivation suppresses Tregs infiltration and induces apoptosis to inhibit HCC carcinogenesis.
Hepatocellular carcinoma (HCC) is characterized by inflammation and immunopathogenesis. Accumulating evidence has shown that the cystathionine β-synthase/hydrogen sulfide (CBS/H2S) axis is involved in the regulation of inflammation. However, roles of CBS in HCC development and immune evasion have not been systematically investigated, and their underlying mechanisms remain elusive. Here, we investigated the roles of CBS in tumor cells and tumor microenvironment of HCC. 236 HCC samples were collected to detect the expression of CBS, cleaved Caspase-3 and paired related homeobox 2 (PRRX2) and the number of immune cells. HCC cell lines were employed to examine the effects of CBS on cellular viability, apoptosis and signaling in vitro. Cbs heterozygous knockout mice, C57BL/6 mice, nude mice and non-obese diabetic severe combined immunodeficiency mice were used to investigate the in vivo functions of CBS. Downregulation of CBS was observed in HCC, and low expression of CBS predicted poor prognosis in HCC patients. CBS overexpression dramatically promoted cellular apoptosis in vitro and inhibited tumor growth in vivo. Activation of the Cbs/H2S axis also reduced the abundance of tumor-infiltrating Tregs, while Cbs deficiency promoted Tregs-mediated immune evasion and boosted tumor growth in Cbs heterozygous knockout mice. Mechanistically, CBS facilitated the expression cleaved Caspase-3 in tumor cells, and on the other hand, suppressed Foxp3 expression in Tregs via inactivating IL-6/STAT3 pathway. As a transcription factor of IL-6, PRRX2 was reduced by CBS. Additionally, miR-24-3p was proven to be an upstream suppressor of CBS in HCC. Our results indicate the antitumor function of CBS in HCC by inactivation of the PRRX2/IL-6/STAT3 pathway, which may serve as a potential target for HCC clinical immunotherapy.


The celiac axis compression syndrome (CACS): critical review in the laparoscopic era.
The celiac axis compression syndrome (CACS) due to median arcuate ligament (MAL) was first described by Harjola in 1963; originating postpandrial abdominal pain, weight loss, epigastric bruit and celiac axis stenosis > 75% in angiographic studies. This clinical condition has been the origin of controversies about its pathogenesis, diagnosis and its long term clinical results. Advances in diagnostic imaging as 64 multidetector-row CT (MDCT), 3-D reconstruction, magnetic resonance (MR) and color duplex ultrasonography, provide better understanding of the syndrome and allow to identify the best candidates for surgical division of MAL fibers. Since the introduction of laparoscopic approach, and also endovascular procedures, in 2000, a new perspective has established in this challenging syndrome. With the occasion of our own experience, a critical review of the syndrome is presented.


A new approach to assessing the health benefit from obesity interventions in children and adolescents: the assessing cost-effectiveness in obesity project.
To report on a new modelling approach developed for the assessing cost-effectiveness in obesity (ACE-Obesity) project and the likely population health benefit and strength of evidence for 13 potential obesity prevention interventions in children and adolescents in Australia. We used the best available evidence, including evidence from non-traditional epidemiological study designs, to determine the health benefits as body mass index (BMI) units saved and disability-adjusted life years (DALYs) saved. We developed new methods to model the impact of behaviours on BMI post-intervention where this was not measured and the impacts on DALYs over the child's lifetime (on the assumption that changes in BMI were maintained into adulthood). A working group of stakeholders provided input into decisions on the selection of interventions, the assumptions for modelling and the strength of the evidence. The likely health benefit varied considerably, as did the strength of the evidence from which that health benefit was calculated. The greatest health benefit is likely to be achieved by the 'Reduction of TV advertising of high fat and/or high sugar foods and drinks to children', 'Laparoscopic adjustable gastric banding' and the 'multi-faceted school-based programme with an active physical education component' interventions. The use of consistent methods and common health outcome measures enables valid comparison of the potential impact of interventions, but comparisons must take into account the strength of the evidence used. Other considerations, including cost-effectiveness and acceptability to stakeholders, will be presented in future ACE-Obesity papers. Information gaps identified include the need for new and more effective initiatives for the prevention of overweight and obesity and for better evaluations of public health interventions.


Motor axonal regeneration after partial and complete spinal cord transection.
We subjected rats to either partial midcervical or complete upper thoracic spinal cord transections and examined whether combinatorial treatments support motor axonal regeneration into and beyond the lesion. Subjects received cAMP injections into brainstem reticular motor neurons to stimulate their endogenous growth state, bone marrow stromal cell grafts in lesion sites to provide permissive matrices for axonal growth, and brain-derived neurotrophic factor gradients beyond the lesion to stimulate distal growth of motor axons. Findings were compared with several control groups. Combinatorial treatment generated motor axon regeneration beyond both C5 hemisection and T3 complete transection sites. Yet despite formation of synapses with neurons below the lesion, motor outcomes worsened after partial cervical lesions and spasticity worsened after complete transection. These findings highlight the complexity of spinal cord repair and the need for additional control and shaping of axonal regeneration.


Nerve growth factor restores p53 function in pituitary tumor cell lines via trkA-mediated activation of phosphatidylinositol 3-kinase.
Two groups of prolactinomas were identified, one slowly proliferating and responsive to bromocriptine and one fast proliferating and bromocriptine resistant. Nerve growth factor (NGF) inhibits proliferation of bromocriptine-resistant cells by mechanisms that are still unclear. The tumor suppressor p53 is one of the key regulators of cell proliferation and in most tumors, but not pituitary adenomas, it is inactivated by genomic mutations. Here we investigated whether in prolactinoma cell lines NGF influences cell cycle-related pathways involving p53. By using conformation-specific antibodies and immunocytochemistry we found that in bromocriptine-resistant cells p53 adopts a mutant conformation that precludes its nuclear translocation and transcriptional activity. NGF administration to these cells refolds p53 into wild-type tertiary structure, promotes its nuclear translocation, and restores its DNA-binding activity as demonstrated by the transcriptional activation of p21Cip1/WAF1 and the resulting down-regulation of different cyclins and cyclin-dependent kinase 2. Inactivation of trkA, but not of p75NTR, and wortmannin prevented NGF-induced p53 nuclear translocation. Thus, in prolactinoma cells p53 is inactivated by conformational mutation and cytoplasmic segregation. This defect is reversible because NGF reconstitutes active p53 in these cells. This effect of NGF is exclusively mediated by trkA through activation of phosphatidylinositol-3-kinase and may be related to its growth-inhibitory action.


High Anisotropy in Tubular Layered Exfoliated KP15.
Two-dimensional (2D) materials with high anisotropic properties, such as black phosphorus and ReS2, show amazing potential for applications in future nanoelectronic and optoelectronic devices. However, degradation of black phosphorus under ambient conditions and the expensiveness of Re block their application. In this study, another layered material, KP15, that has highly anisotropic properties was successfully prepared. The detailed crystal structure and electron-density distribution calculation reveal that KP15 exhibits an anisotropic layered structure with two rows of P tubes connected by K atoms that are antiparallel in a single layer. Outstanding chemical stability, angular dependence of the Raman response, excitation, and exciton emission at room temperature have been found in exfoliated KP15 nanoribbons. Importantly, the exciton emission at room temperature suggests the existence of a large exciton binding energy. Our results indicate that, because this layered material, KP15, has high anisotropic properties and ultrachemical stability and is derived from abundant raw materials, it has great potential for applications in optoelectronic devices.


Transition readiness and quality of life in emerging adult college students.
To examine the relative contribution of transition readiness (i.e., healthcare self-management) to health-related quality of life (HRQoL) among emerging adult (EA) college students without a chronic medical condition (CMC).Participants: College students (n = 2372; Mage = 19.32, SD = 1.26) from a Midwestern university.Methods: Participants completed online measures of demographics, HRQoL, and transition readiness.Results: Hierarchical regression analyses found transition readiness accounted an additional 3-4% of the variability in mental and physical HRQoL (p < .001), beyond demographic factors. 11.3% of EAs reported overall mastery of transition readiness, with navigating health insurance being the weakest area.Conclusions: Findings support the consensus that transition readiness is relevant to HRQoL for all EAs, including those without a CMC. EAs without a CMC demonstrate relatively weak transition readiness skills. Primary and university-based healthcare might consider programs supporting transition readiness and HRQoL among underresourced EAs.


Ski pole thumb injury.
Disabling injuries can occur in the area of the MP joint of the thumb when a skier falls against the planted ski pole while holding the ski strap in the usual fashion. This is presently the most common ski injury of the upper extremity. It is important to determine if instability has resulted, because there may be disruption of the ulnar aspect of joint capsule as well as of the extensoradductor hood mechanism. If this has occurred, it is immediately to prevent the development of the chronic "gamekeeper's thumb."


Brainstem auditory evoked responses in coma due to meningoencephalitis.
Prognosticating the outcome of an unconscious patient continues to pose a serious challenge to the clinicians. BAERs are the latest addition to neurological diagnostic aids for predicting the outcome of coma. The relative value of BAERs in predicting the outcome of 15 comatosed meningoencephalitis patients has been studied. The results points to a rôle of BAERs in the detection of brain stem dysfunction in a large majority of patients. However, when used as a prognostic indicant, the traditional bed-side clinical assessment (GCS and vestibulo-ocular cold caloric response) still holds a slight advantage over advanced technology. BAERs may have a place in assessing brain stem dysfunction in neurologic conditions where an adequate clinical assessment may not be possible.


Gating Modulation of the Tumor-Related Kv10.1 Channel by Mibefradil.
Several reports credit mibefradil with tumor suppressing properties arising from its known inhibition of Ca2+ currents. Given that mibefradil (Mb) is also known to inhibit K+ channels, we decided to study the interaction between this organic compound and the tumor-related Kv10.1 channel. Here we report that Mb modulates the gating of Kv10.1. Mb induces an apparent inactivation from both open and early closed states where the channels dwell at hyperpolarized potentials. Additionally, Mb accelerates the kinetics of current activation, in a manner that depends on initial conditions. Our observations suggest that Mb binds to the voltage sensor domain of Kv10.1 channels, thereby modifying the gating of the channels in a way that in some, but not all, aspects opposes to the gating effects exerted by divalent cations. J. Cell. Physiol. 232: 2019-2032, 2017. © 2016 Wiley Periodicals, Inc.


Molecular and prognostic distinction between serous ovarian carcinomas of varying grade and malignant potential.
Profiles of gene transcription have begun to delineate the molecular basis of ovarian cancer, including distinctions between carcinomas of differing histology, tumor progression and patient outcome. However, the similarities and differences among the most commonly diagnosed noninvasive borderline (low malignant potential, LMP) lesions and invasive serous carcinomas of varying grade (G1, G2 and G3) have not yet been explored. Here, we used oligonucleotide arrays to profile the expression of 12,500 genes in a series of 57 predominantly stage III serous ovarian adenocarcinomas from 52 patients, eight with borderline tumors and 44 with adenocarcinomas of varying grade. Unsupervised and supervised analyses showed that LMP lesions were distinct from high-grade serous adenocarcinomas, as might be expected; however, well-differentiated (G1) invasive adenocarcinomas showed a strikingly similar profile to LMP tumors as compared to cancers with moderate (G2) or poor (G3) cellular differentiation, which were also highly similar. Comparative genomic hybridization of an independent cohort of five LMP and 63 invasive carcinomas of varying grade demonstrated LMP and G1 were again similar, exhibiting significantly less chromosomal aberration than G2/G3 carcinomas. A majority of LMP and G1 tumors were characterized by high levels of p21/WAF1, with concomitant expression of cell growth suppressors, gadd34 and BTG-2. In contrast, G2/G3 cancers were characterized by the expression of genes associated with the cell cycle and by STAT-1-, STAT-3/JAK-1/2-induced gene expression. The distinction between the LMP-G1 and G2-G3 groups of tumors was highly correlated to patient outcome (chi(2) for equivalence of death rates=7.681189; P=0.0056, log-rank test). Our results are consistent with the recent demonstration of a poor differentiation molecular 'meta-signature' in human cancer, and underscore a number of cell-cycle- and STAT-associated targets that may prove useful as points of therapeutic intervention for those patients with aggressive disease.


Benzofuran derivatives from alkynyl-substituted benzynes and aryl halides.
A palladium(0)-catalyzed cascade reaction for the efficient synthesis of 2,3-disubstituted benzofuran derivatives 3 containing a 3-trisubstituted alkene functional group in moderate yields from alkynyl-substituted benzynes 1 and aryl halides 2 has been developed. This method provides an efficient and alternative approach to benzofurans which are very useful heterocyclic compounds with biological and pharmacological potentials. A plausible mechanism involving intramolecular ene reaction, intermolecular insertion, and β-H elimination is proposed.


[Expression of cytochrome P450 related genes in oral submucous fibrosis tissue].
To examine the expression of cytochrome P450 related genes in oral submucous fibrosis tissue and to investigate the possible role of the genes in pathogenesis of oral submucous fibrosis (OSF). Buccul mucosa tissues were obtained from OSF patients in early, medium and advanced stages, with each stage including 10 patients. Normal buccul mucosa tissues were collected from 10 patients undergoing oral and maxillofacial surgery as control. Oral submucous fibrosis-related genes were analysed by cDNA chips, and the results were submitted to the gene network database. Differentially expressed genes related to the pathway of CYP metabolism were indentifyed by the database analysis. Reverse transcription-polymerase chain reaction (RT-PCR) was used to verify the results from cDNA chips by increasing sample volume. There were eight genes [CYP2B6, CYP2C18, CYP2F1, CYP3A5, microsomal glutathione S-transferase 2 (MGST2), alcohol dehydrogenase (ADH), UDP glucuronosyl transferase 2B15 (UGT2B15), ADH1C] which were related to the pathway of CYP metabolism. These genes were low expressed in all stages of OSF (P < 0.001).There were no differences in genes expression among the three stages of OSF (P > 0.05). There were down-regulated genes related to the pathway of CYP metabolism in oral submucous fibrosis tissue. The ability of the pathway of CYP to metabolize and clear betel nut ingredients was reduced in OSF patients, which may play a role in the pathogenesis of OSF.


Body Builder's Shoulder: Posterior Labrum Periosteal Sleeve Avulsion (POLPSA) and Glenoid Posterior Rim Stress Fracture due to Intense Bench Pressing.
Shoulder overuse, both occupational and sports-related, is a major cause of shoulder pain with an estimated incidence of 0.9%-2.5% in the general population and a prevalence of 7%-27% in Europe and United States. We report on a young amateur bodybuilder presenting with a complex shoulder overuse lesion. A posterior labrum periosteal sleeve avulsion (POLPSA) with a chondral lesion of the posterior glenoid cavity and a SLAP lesion was diagnosed. Case presentation. A 33-year-old male construction worker complained of 9 months worsening right shoulder pain. He was an amateur body builder who would bench press heavy weights (up to 170 kg). A magnetic resonance arthrogram showed a posterior labrum sleeve avulsion, a stress chondral fracture of the posterior glenoid cavity and a SLAP lesion. Arthroscopic repair of the bicipital anchor, posterior labrum fixation and removal of the chondral fragment, proved successful and allowed the patient to return to his previous sports activity. Bench press creates major forces along the anteroposter axis of the upper limbs, pushing the humeral head posteriorly and increasing joint reaction force on the posterior glenoid quadrant considerably as the scapula is locked resting on the bench. This may result in a tendency for the humeral head to subluxate posteriorly which, aggravated by the high number of repetitions, puts the posterior labrum and capsula under very high stress eventually leading to labrum failure. Arthroscopic repair was shown to restore shoulder function in these athletes.


Dialysis patients who smoke are more hypertensive, more fluid overloaded and take more antihypertensive medications than nonsmokers.
Background: Smoking remains a powerful risk factor for death in end-stage renal disease (ESRD) and so is the presence of fluid overload. The relationship between smoking, blood pressure (BP) control and volume overload is insufficiently explored in patients on maintenance dialysis.Methods: This is a retrospective cross-sectional cohort study, utilizing existing patients' data generated during routine ESRD care, including bimonthly protocol bioimpedance fluid assessment of the volume status.Results: We analyzed the data of 63 prevalent patients receiving thrice weekly maintenance hemodiafiltration treatments at one rural dialysis unit in Hungary. The cohort's mean ± SD age was 61.5 ± 15.3 years; 65% male, 38% diabetic, with a mean arterial blood pressure (MAP) 99.5 ± 16.8 mmHg and Charlson score 3.79 ± 2.04. Of these, 38 patients were nonsmokers and 25 smokers. The nonsmokers' MAP was 94.3 ± 14.0 versus smokers' 105.9 ± 18.9 mmHg (p: .002); nonsmokers took an average 0.73 ± 0.92 antihypertensive medications vs. 1.73 ± 1.21 for smokers (p: .0001). The distribution of taking more antihypertensive medications is skewed toward a higher number among the smokers (2x5 chi square p: .004). By bioimpedance spectroscopy, nonsmokers had an average 10.93 ± 7.65 percent overhydration (OH) over the extracellular space compared to 17.63 ± 8.98 in smokers (p: .005).Conclusions: Smoking may be a significant mediator of not only BP but also of chronic fluid overload in ESRD patents. Additional, larger studies are needed to explore the mechanistic link between smoking and volume overload.


Anal fissure nanocarrier of lercanidipine for enhanced transdermal delivery: formulation optimization, ex vivo and in vivo assessment.
Pathogenesis of anal fissure (AF) is associated with raised resting anal pressures (RAP) involving contraction of smooth muscle. Therefore, the drug delivery strategy should be customized to reduce this raised RAP. In this investigation, in order to achieve this task, a transdermal nanoemulsion (NE) gel of lercanidipine (LER) was developed and optimized to evaluate its permeation ability and in vivo performance. Further, the same formulation was explored for droplet size analysis, zeta potential measurement and stability studies. Pseudo-ternary phase diagram was constructed to determine NE region. The NE was optimized (OPT) by employing three-factor, three-level Box-Behnken design expert software; the independent variables decided were composition of oil, Smix and water and dependent variables, that is, responses were cumulative amount of drug permeated across rat abdominal skin in 24 h (Q24), steady-state flux (Js) and viscosity. The in vivo efficacy was assessed by measuring anorectal pressure in male Wistar rats. The OPT NE formulation, composed of Capryol 90 (12.70% w/w), Cremophor EL (18.0% w/w), Transcutol HP (18.0% w/w) and water (60.00%) w/w was found to have permeation flux of 60.27 µg/cm(2)/h, release of 1699.52 µg/24 h and 491.95 cP viscosity. In addition, a small average droplet size (82.71 ± 9.96 nm) and long-term stability at room temperature (1.666 years) was observed. The in vivo investigation demonstrated direct evidence on significant reduction (27.75%) in anorectal pressure over a period of 4 h. These preliminary finding suggested that NE-based gel system of LER may provide promising perspective in management of AF.


[Anomalies of the biliary tract. Review and report about two distal intrapancreatic common bile ducts (author's transl)].
A brief review about occurrence and experience of abnormalities of the biliary system is reported. The knowledge of these rare anomalies is important for the difficult diagnosis, an effective surgical therapy, and to avoide diagnostical misconstructions. 2 cases of distal intrapancreatic common bile ducts with misleading symptoms are described, which had not been yet reported in the literature.


Physical fitness status of Egyptian children aged 9-18 years.
Male (n = 399) and female (n = 311) Egyptian school children, aged 9-18 yrs, had their fitness evaluated using the 6-item AAHPER test. Comparisons of the 50th percentiles of the AAHPER norms with the median scores for the Egyptian sample revealed that the latter were substantially below average fitness levels. Egyptian boys performed significantly better than girls on all comparable test items, even when the effects of age, height, and weight were held constant by covariance. Eight weeks of twice weekly intensified physical education instruction produced significant improvements in all test items for both sexes.


Post-Chemotherapy Rebound Thymic Hyperplasia Mimicking Relapse in Breast Implant-Associated Anaplastic Large Cell Lymphoma: A Case Report.
Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an unusual form of T-cell non-Hodgkin lymphoma. Surgical management is essential; however, adjuvant therapy is recommended for advanced stages of cancer. A 40-year-old woman with textured silicone implants placed 7 years earlier, presented with breast nodules. Physical examination and computed tomography (CT) revealed a left parasternal mass, 2 left-breast nodules, and axillary lymphadenopathies. A soft-tissue lesion in the anterior mediastinum consistent with thymic remnants was detected. BIA-ALCL was diagnosed based on ultrasound-guided core biopsies of an axillary lymph node and a breast nodule. She underwent total bilateral capsulectomy and received anthracycline-based adjuvant chemotherapy. End-of-treatment positron emission tomography-computed tomography (PET-CT) scan at 4 months showed no evidence of disease, except for the persistence of the mediastinal lesion (Deauville score 4). Three months later, a new PET-CT scan showed enlargement of the lesion and increased radiotracer uptake, suggesting metabolic progression. A mediastinal biopsy was performed and rebound thymic hyperplasia (RTH) was observed in the histopathologic study. Once complete remission (CR) was achieved, the patient was followed up continually and has shown no signs of relapse to date. Further studies are required to determine the best adjuvant therapy for advanced BIA-ALCL. RTH may be suspected when thymic enlargement without the involvement of other areas is observed in patients with cancer. Mediastinal biopsy is mandatory to rule out relapse.


Central amygdala lesions inhibit pontine nuclei acoustic reactivity and retard delay eyeblink conditioning acquisition in adult rats.
In delay eyeblink conditioning (EBC) a neutral conditioned stimulus (CS; tone) is repeatedly paired with a mildly aversive unconditioned stimulus (US; periorbital electrical shock). Over training, subjects learn to produce an anticipatory eyeblink conditioned response (CR) during the CS, prior to US onset. While cerebellar synaptic plasticity is necessary for successful EBC, the amygdala is proposed to enhance eyeblink CR acquisition. In the current study, adult Long-Evans rats received bilateral sham or neurotoxic lesions of the central nucleus of the amygdala (CEA) followed by 1 or 4 EBC sessions. Fear-evoked freezing behavior, CS-mediated enhancement of the unconditioned response (UR), and eyeblink CR acquisition were all impaired in the CEA lesion rats relative to sham controls. There were also significantly fewer c-Fos immunoreactive cells in the pontine nuclei (PN)-major relays of acoustic information to the cerebellum-following the first and fourth EBC session in lesion rats. In sham rats, freezing behavior decreased from session 1 to 4, commensurate with nucleus-specific reductions in amygdala Fos+ cell counts. Results suggest delay EBC proceeds through three stages: in stage one the amygdala rapidly excites diffuse fear responses and PN acoustic reactivity, facilitating cerebellar synaptic plasticity and the development of eyeblink CRs in stage two, leading, in stage three, to a diminution or stabilization of conditioned fear responding.


Chemical dissection of the APC Repeat 3 multistep phosphorylation by the concerted action of protein kinases CK1 and GSK3.
A crucial event in machinery controlled by Wnt signaling is the association of beta-catenin with the adenomatous polyposis coli (APC) protein, which is essential for the degradation of beta-catenin and requires the multiple phosphorylation of APC at six serines (1501, 1503, 1504, 1505, 1507, and 1510) within its repeat three (R3) region. Such a phosphorylation is believed to occur by the concerted action of two protein kinases, CK1 and GSK3, but its mechanistic aspects are a matter of conjecture. Here, by combining the usage of variably phosphorylated peptides reproducing the APC R3 region and Edman degradation assisted localization of residues phosphorylated by individual kinases, we show that the process is initiated by CK1, able to phosphorylate S1510 and S1505, both specified by non-canonical determinants. Phosphorylation of S1505 primes subsequent phosphorylation of S1501 by GSK3. In turn, phospho-S1501 triggers the hierarchical phosphorylation of S1504 and S1507 by CK1. Once phosphorylated, S1507 primes the phosphorylation of both S1510 and S1503 by CK1 and GSK3, respectively, thus completing all six phosphorylation steps. Our data also rule out the intervention of CK2 despite the presence of a potential CK2 phosphoacceptor site, S1510LDE, in the R3 repeat. S1510 is entirely unaffected by CK2, while it is readily phosphorylated even in the unprimed peptide by CK1delta but not by CK1gamma. This discloses a novel motif significantly different from non-canonical sequences phosphorylated by CK1 in other proteins, which appears to be specifically recognized by the delta isoform of CK1.


Survey on knowledge, attitude, acceptance and related factors among pregnant women in Thailand regarding antenatal thalassaemia screening.
Thalassaemia is a common haematologic health condition in Southeast Asian countries (SEA) including Thailand. Reducing the birth of new thalassaemia cases is an effective method to control disease. The background level of knowledge and attitude of pregnant women on the disease influences their decision to perform antenatal screening. Unfortunately, the information about pregnant women's knowledge and attitude on antenatal thalassaemia screening in a developing country such as Thailand is lacking. We therefore conducted this cross-sectional study to examine patients' knowledge and to evaluate the factors which influence the patient's knowledge and attitude on antenatal thalassaemia screening. 1006 pregnant women who attended antenatal care at the Maha Chakri Sirindhorn Medical Center, Faculty of Medicine, Srinakharinwirot University, Ongkharak, Nakhon Nayok, Thailand were enrolled. We found that women's knowledge on antenatal thalassaemia screening is low. A maternal age of ≥35 years was associated with a higher level of knowledge. A higher level of education and multigravidity, a family history of thalassaemia and a positive level of attitude were found more likely to have higher scores for knowledge. A higher level of education and level of knowledge score were also more likely to have a positive attitude score, but multigravidity negatively affected the attitude score. Effective counselling should be monitored among women with a lower levels of education, those with no family history of thalassaemia, and in primigravidas. Lastly, a concurrent Down syndrome screening or foetal sex determination may be useful incentives to encourage the decision to undergo screening. Impact statement What is already known about this subject? Screening for the paternal and maternal thalassaemia carrier status is important for reducing the incidence of severely thalassaemia-affected children. Poorer education and receiving genetic counselling for the first time were the predictive factors for the low post-counselling knowledge in genetic counselling before second trimester genetic amniocentesis. What do the results of this study add? Pregnant women's knowledge of antenatal thalassaemia screening was low. We found that pregnant women aged ≥35 years had a higher level of knowledge. Women with a higher level of education, multigravidity, the presence of a family history of thalassaemia and a positive attitude were more likely to have higher scores for knowledge. A higher level of education and level of knowledge score were also more likely to have a positive attitude score but multigravidity negatively affected the attitude score. The encouraging factors, such as an adjunctive Down syndrome screening or foetal structural screening or foetal sex determination may be useful as the incentive tools. What are the implications of these finding for clinical practice and/or further research? The awareness of a possible incorrect understanding is important for the antenatal counselling in the developing countries. Intensive monitoring of effective counselling using a post-counselling test should be scheduled. The methods of effective counselling for antenatal thalassaemia in developing countries should be evaluated.


Systematic analysis of nucleation-dependent polymerization reveals new insights into the mechanism of amyloid self-assembly.
Self-assembly of misfolded proteins into ordered fibrillar aggregates known as amyloid results in numerous human diseases. Despite an increasing number of proteins and peptide fragments being recognised as amyloidogenic, how these amyloid aggregates assemble remains unclear. In particular, the identity of the nucleating species, an ephemeral entity that defines the rate of fibril formation, remains a key outstanding question. Here, we propose a new strategy for analyzing the self-assembly of amyloid fibrils involving global analysis of a large number of reaction progress curves and the subsequent systematic testing and ranking of a large number of possible assembly mechanisms. Using this approach, we have characterized the mechanism of the nucleation-dependent formation of beta(2)-microglobulin (beta(2)m) amyloid fibrils. We show, by defining nucleation in the context of both structural and thermodynamic aspects, that a model involving a structural nucleus size approximately the size of a hexamer is consistent with the relatively small concentration dependence of the rate of fibril formation, contrary to expectations based on simpler theories of nucleated assembly. We also demonstrate that fibril fragmentation is the dominant secondary process that produces higher apparent cooperatively in fibril formation than predicted by nucleated assembly theories alone. The model developed is able to explain and predict the behavior of beta(2)m fibril formation and provides a rationale for explaining generic properties observed in other amyloid systems, such as fibril growth acceleration and pathway shifts under agitation.


In vitro performance characteristics of a high-flux hemodialyzer with a novel polyester-polymer-alloy (PEPA) membrane.
Despite improvements in hemodialyzers with respect to their clearance of middle and high molecular mass molecules, accumulation of specific solutes in the circulation of dialysis patients continues to be a medical problem. A new membrane material, polyester-polymer alloy (PEPA) which has been developed to have a filtration profile akin to that of the natural kidney, is now being used in hemodialyzers. This study evaluates the performance of a PEPA-based hemodialyzer alongside a selection of available competing high-flux dialyzers using official standardized methods. The new membrane material appears to be a viable alternative which offers performance at least as good as that of the competition. The promising results obtained with the PEPA membrane suggest that a detailed clinical performance study should be undertaken.


Role of cyclophilin B in tumorigenesis and cisplatin resistance in hepatocellular carcinoma in humans.
Cyclophilin B (CypB) performs diverse roles in living cells, but its role in hepatocellular carcinoma (HCC) is largely unclear. To reveal its role in HCC, we investigated the induction of CypB under hypoxia and its functions in tumor cells in vitro and in vivo. Here, we demonstrated that hypoxia-inducible factor 1α (HIF-1α) induces CypB under hypoxia. Interestingly, CypB protected tumor cells, even p53-defective HCC cells, against hypoxia- and cisplatin-induced apoptosis. Furthermore, it regulated the effects of HIF-1α, including those in angiogenesis and glucose metabolism, via a positive feedback loop with HIF-1α. The tumorigenic and chemoresistant effects of CypB were confirmed in vivo using a xenograft model. Finally, we showed that CypB is overexpressed in 78% and 91% of the human HCC and colon cancer tissues, respectively, and its overexpression in these cancers reduced patient survival. These results indicate that CypB induced by hypoxia stimulates the survival of HCC via a positive feedback loop with HIF-1α, indicating that CypB is a novel candidate target for developing chemotherapeutic agents against HCC and colon cancer.


Porobeltraniella gen. nov. to accommodate two species of Beltraniella.
The genus Beltraniella Subramanian is characterized by setiform conidiophores with radially lobed basal cells, separating cells and lageniform conidia with the distal free end truncate, proximal end rostrate, with a subhyaline transverse band at equatorial zone. Beltraniella porosa and Beltraniella patilii are two species that show characteristics distinct from Beltraniella: They have sterile lateral setae arising at the conidiogenous apparatus and several equatorial pores in place of the continuous band. A new genus, Porobeltraniella, is described to accommodate them.


Mechanism of inhibition of endothelin-1-stimulated proteoglycan and collagen synthesis in rat articular chondrocytes.
The aim of this study was to determine the effects of endothelin-1 (ET-1) on proteoglycan (PG) and collagen synthesis by rat articular chondrocytes (RAC). PG and collagen synthesis was measured by [(35)S]-sulphate and [(3)H]-glycine incorporation, respectively into monolayers of confluent RAC exposed to ET-1 (10(-11) M-10(-7) M). ET-1 stimulated PG and collagen synthesis in these cells in a concentration-dependent manner during the first 24 h of incubation. Prolonged contact of the cells with ET-1 resulted in a gradual decrease, and finally, inhibition of ET-1 effects. This inhibition is mediated by nitric oxide (NO) released in response to ET-1 since: (1) nitric oxide synthase inhibitor, nitro-L-arginine-methyl ester (L-NAME), enhanced both basal and ET-1-induced [(35)S]-sulphate and [(3)H]-glycine incorporations; (2) sodium nitroprusside (SNP), which spontaneously releases NO, inhibited both basal and ET-1-induced incorporations, and was also able to suppress the effects of L-NAME; (3) NO levels in the culture media were also correlated with the inhibition of [(35)S]-sulphate and [(3)H]-glycine incorporation; and (4) SNP also inhibited aggrecan and collagen II transcriptions, probably via cGMP. This effect was mimicked with 8-bromo-cGMP. Interestingly, the LY83583, which blocks the NO-dependent production and release of cGMP, inhibited PG-collagen synthesis but had no effect on their mRNA expressions. Thus, normal levels of cGMP appeared to be necessary for PG-collagen synthesis, whereas decreased levels are detrimental. In conclusion, NO, produced by rat AC in response to ET-1, counteracts the stimulation and finally induces inhibition of PG-collagen synthesis by ET-1 in these cells but NO-induced cGMP is only partially responsible for this inhibition.


The Economic Value of the Centers for Disease Control and Prevention Carbapenem-Resistant Enterobacteriaceae Toolkit.
OBJECTIVEWhile previous work showed that the Centers for Disease Control and Prevention toolkit for carbapenem-resistant Enterobacteriaceae (CRE) can reduce spread regionally, these interventions are costly, and decisions makers want to know whether and when economic benefits occur.DESIGNEconomic analysisSETTINGOrange County, CaliforniaMETHODSUsing our Regional Healthcare Ecosystem Analyst (RHEA)-generated agent-based model of all inpatient healthcare facilities, we simulated the implementation of the CRE toolkit (active screening of interfacility transfers) in different ways and estimated their economic impacts under various circumstances.RESULTSCompared to routine control measures, screening generated cost savings by year 1 when hospitals implemented screening after identifying ≤20 CRE cases (saving $2,000-$9,000) and by year 7 if all hospitals implemented in a regional coordinated manner after 1 hospital identified a CRE case (hospital perspective). Cost savings was achieved only if hospitals independently screened after identifying 10 cases (year 1, third-party payer perspective). Cost savings was achieved by year 1 if hospitals independently screened after identifying 1 CRE case and by year 3 if all hospitals coordinated and screened after 1 hospital identified 1 case (societal perspective). After a few years, all strategies cost less and have positive health effects compared to routine control measures; most strategies generate a positive cost-benefit each year.CONCLUSIONSActive screening of interfacility transfers garnered cost savings in year 1 of implementation when hospitals acted independently and by year 3 if all hospitals collectively implemented the toolkit in a coordinated manner. Despite taking longer to manifest, coordinated regional control resulted in greater savings over time.Infect Control Hosp Epidemiol 2018;39:516-524.


Increased proto-oncogene expression in peripheral blood T lymphocytes from patients with systemic sclerosis.
The expression of c-myc, c-myb, and c-ras proto-oncogenes, determined using RNA hybridization techniques (slot-blot), was significantly increased in peripheral blood T lymphocytes, but not in B cells, from 17 patients with systemic sclerosis with diffuse scleroderma, compared with the expression in normal control subjects. The magnitude of expression of c-myc and c-myb tended to be higher in patients with early, active disease. These results demonstrate an in vivo activation of T cells from systemic sclerosis patients, which may play an important role in the pathogenesis of the disease.


Self-Registered Self-Assembly of Block Copolymers.
Directed self-assembly (DSA) of block copolymer (BCP) thin films, especially with density multiplication, is one of the most promising options for further improving resolution and throughput in nanolithography. However, controlling defect density has been one of the major hurdles for many DSA applications. Both thermodynamically and kinetically, defect-free patterns favor the use of low density multiplication factors and thinner films, which undermine the promise of enhanced resolution and the formation of robust masks for pattern transfer. Here, we demonstrate a self-registered self-assembly method to enable nearly perfect DSA on loosely defined chemical patterns with high density multiplication factor. Self-registered self-assembly involves two DSA steps. In the first step, an ultrathin BCP blend film is used to obtain vanishingly low defect densities. Concurrently as the film is annealed, preloaded chemical markers separate into the different polymer blocks and graft to the substrate locking in a new chemical contrast pattern with 1:1 feature registration. After thorough removal of the blend film, the remaining self-registered chemical pattern can establish defect-free DSA of thick BCP films.


Hypoxemia during hemodialysis.
Decrease in arterial oxygen tension has been reported during hemodialysis.(1-3) The etiology of the hypoxemia has not been clearly demonstrated. Intravascular leukostasis,(1) pulmonary arterial microembolization,(3) and loss of CO(2) through the dialyzer are some of the explanations given for this abnormality.(2,4) Why a small percentage of hemodialysis patients develop profound, symptomatic hypoxemia has not been satisfactorily explained.


Development of a Loop-Mediated Isothermal Amplification Assay for the Detection of Dickeya spp.
Dickeya and Pectobacterium spp. are responsible for soft-rotting diseases of several plant species, some with overlapping host range. On potato, symptoms caused by these pathogens cannot be clearly differentiated. Disease results in the downgrading and rejection of potato seed, thus requiring additional phytosanitary restrictions across Northern Europe and other parts of the world. In an effort to provide a more timely and accurate diagnostic to distinguish these two groups of pathogens, a method for detecting Dickeya spp. using loop-mediated isothermal amplification (LAMP) was developed. The LAMP assay can be used to test crude extracts prepared directly from symptomatic lesions. The entire test can be completed in less than 30 min, making it faster than the current diagnostic standard, the pelADE conventional polymerase chain reaction. Additionally, the LAMP assay was able to detect Dickeya DNA in samples spiked with varying amounts of Pectobacterium DNA, thus demonstrating the highly specific and sensitive nature of the assay, which can be applied on survey samples with mixed soft-rotting bacterial populations.


Competing risks as a multi-state model.
This paper deals with the competing risks model as a special case of a multi-state model. The properties of the model are reviewed and contrasted to the so-called latent failure time approach. The relation between the competing risks model and right-censoring is discussed and regression analysis of the cumulative incidence function briefly reviewed. Two real data examples are presented and a guide to the practitioner is given.


Induction of high level IL-2 production in CD4+8- T helper lymphocytes requires post-thymic development.
Triggering of the CD3:TCR complex by optimal concentrations of anti-CD3, anti-TCR beta-chain, and allogeneic stimulator cells induced dramatically higher levels (fivefold for anti-CD3, greater than 10-fold for anti-TCR beta-chain, 84-fold for alloantigen) of IL-2 production in spleen CD4+8- T cells than their thymic counterparts, despite comparable levels of CD3 and TCR beta-chain expression. The nature of the reduced IL-2 production was examined by analysis of anti-CD3-induced IL-2 production at the single cell level. The frequency of IL-2-producing cells in spleen CD4+8- T cells (40.0%) was approximately threefold that of thymus CD4+8- T cells (14.5%). Furthermore, the average IL-2 levels among positive IL-2 producers was also approximately threefold higher in spleen CD4+8- T cells than their thymic counterparts. Adoptive transfer of purified Thy-1.2+ CD4+8- T cells into Thy-1.1-congenic hosts provided a physiologic and histocompatible system that enabled identification of transferred donor (Thy-1.2+) among a sea of host (Thy-1.2-) CD4+ T cells, whose immune function with respect to IL-2 inducibility was examined after isolation by electronic cell sorting. Donor CD4+ T cells thus isolated from host spleen shortly (1 day) after i.v. transfer of thymus CD4+8- T cells were similar to freshly isolated thymus CD4+8- T cells in that they both produced little IL-2 in response to anti-CD3. However, by day 3 post-transfer, IL-2 production by donor CD4+8- T cells had more than doubled and by day 8, they produced IL-2 levels comparable to those of host spleen CD4+8- T cells. A similar acquisition of high level IL-2 inducibility in thymus CD4+8- T cells upon i.v. transfer into Thy-1.1-congenic hosts was also observed using allogeneic cells as the stimulus of IL-2 production. When thymus CD4+8- T cells were intra-thymically transferred into Thy-1.1-congenic hosts, those donor cells that emigrated to the periphery became high IL-2 producers in a time-dependent manner, whereas those that remained inside the thymus showed no signs of up-regulation in IL-2 inducibility. Intrathymic transfer of CD4-8- thymocytes revealed that the most recent thymic emigrant CD4+8- T cells contained few IL-2-producing cells and were not functionally mature with respect to high level IL-2 inducibility.


De-noising and retrieving algorithm of Mie lidar data based on the particle filter and the Fernald method.
The signal-to-noise ratio (SNR) of an atmospheric lidar decreases rapidly as range increases, so that maintaining high accuracy when retrieving lidar data at the far end is difficult. To avoid this problem, many de-noising algorithms have been developed; in particular, an effective de-noising algorithm has been proposed to simultaneously retrieve lidar data and obtain a de-noised signal by combining the ensemble Kalman filter (EnKF) and the Fernald method. This algorithm enhances the retrieval accuracy and effective measure range of a lidar based on the Fernald method, but sometimes leads to a shift (bias) in the near range as a result of the over-smoothing caused by the EnKF. This study proposes a new scheme that avoids this phenomenon using a particle filter (PF) instead of the EnKF in the de-noising algorithm. Synthetic experiments show that the PF performs better than the EnKF and Fernald methods. The root mean square error of PF are 52.55% and 38.14% of that of the Fernald and EnKF methods, and PF increases the SNR by 44.36% and 11.57% of that of the Fernald and EnKF methods, respectively. For experiments with real signals, the relative bias of the EnKF is 5.72%, which is reduced to 2.15% by the PF in the near range. Furthermore, the suppression impact on the random noise in the far range is also made significant via the PF. An extensive application of the PF method can be useful in determining the local and global properties of aerosols.


Plant Cysteine Oxidase Oxygen-Sensing Function Is Conserved in Early Land Plants and Algae.
All aerobic organisms require O2 for survival. When their O2 is limited (hypoxia), a response is required to reduce demand and/or improve supply. A hypoxic response mechanism has been identified in flowering plants: the stability of certain proteins with N-terminal cysteine residues is regulated in an O2-dependent manner by the Cys/Arg branch of the N-degron pathway. These include the Group VII ethylene response factors (ERF-VIIs), which can initiate adaptive responses to hypoxia. Oxidation of their N-terminal cysteine residues is catalyzed by plant cysteine oxidases (PCOs), destabilizing these proteins in normoxia; PCO inactivity in hypoxia results in their stabilization. Biochemically, the PCOs are sensitive to O2 availability and can therefore act as plant O2 sensors. It is not known whether oxygen-sensing mechanisms exist in other phyla from the plant kingdom. Known PCO targets are only conserved in flowering plants, however PCO-like sequences appear to be conserved in all plant species. We sought to determine whether PCO-like enzymes from the liverwort, Marchantia polymorpha (MpPCO), and the freshwater algae, Klebsormidium nitens (KnPCO), have a similar function as PCO enzymes from Arabidopsis thaliana. We report that MpPCO and KnPCO show O2-sensitive N-terminal cysteine dioxygenase activity toward known AtPCO ERF-VII substrates as well as a putative endogenous substrate, MpERF-like, which was identified by homology to the Arabidopsis ERF-VIIs transcription factors. This work confirms functional and O2-dependent PCOs from Bryophyta and Charophyta, indicating the potential for PCO-mediated O2-sensing pathways in these organisms and suggesting PCO O2-sensing function could be important throughout the plant kingdom.


Applying Electrospun Gelatin/Poly(lactic acid-co-glycolic acid) Bilayered Nanofibers to Fabrication of Meniscal Tissue Engineering Scaffold.
The menisci are fibrocartilaginous tissues composed primarily of an interlacing network of collagen fibers with nanoscale diameter. Electrospinning is a suitable process of producing nanoscale fibers that mimic collagen fibers. In this study, a bilayered scaffold (group B), which consists of a gelatin nanofiber mesh and a PLGA nanofiber mesh, has been fabricated through an electrospinning method. At the same time, we electrospun pure PLGA fibrous mesh (group A) and gelatin/PLGA composite fibrous mesh (group C) as control groups. In order to compare all scaffold morphologies, the scaffolds were imaged by SEM and some parameters were measured and analyzed as following: Diameters of fibrils are from the smallest of less than average 0.14 μm for group C to the biggest of nearly average 0.38 μm for group B. The scaffolds pore diameters are from average 4.9 μm for group A to average 11.2 μm for group B. Porosity rates show that the group B has the highest porosity rate at about 91%. The scaffolds' properties were compared and analyzed, including hydrophilicity property (water contact angle) and mechanical properties (tensile strength). The results of water contact angle showed the group B is the most hydrophil among the groups. The results of tensile strength showed the tensile strength of group C is the weakest among the groups. All the results showed significant differences between the groups. Finally, in vitro, the meniscal cells derived from New Zealand white rabbits menisci were seeded in the scaffolds. We observed the cells proliferation behavior in the scaffolds. All above demonstrates that a bi-layered gelatin/PLGA scaffold reveals not only concurrent effects of mechanics and cytocompatibility in a fibrous context, but also a promising scaffold for future meniscal repair strategies.


Connectomes for 40,000 UK Biobank participants: A multi-modal, multi-scale brain network resource.
We mapped functional and structural brain networks for more than 40,000 UK Biobank participants. Structural connectivity was estimated with tractography and diffusion MRI. Resting-state functional MRI was used to infer regional functional connectivity. We provide high-quality structural and functional connectomes for multiple parcellation granularities, several alternative measures of interregional connectivity, and a variety of common data pre-processing techniques, yielding more than one million connectomes in total and requiring more than 200,000 h of compute time. For a single subject, we provide 28 out-of-the-box versions of structural and functional brain networks, allowing users to select, e.g., the parcellation and connectivity measure that best suit their research goals. Furthermore, we provide code and intermediate data for the time-efficient reconstruction of more than 1000 different versions of a subject's connectome based on an array of methodological choices. All connectomes are available via the UK Biobank data-sharing platform and our connectome mapping pipelines are openly available. In this report, we describe our connectome resource in detail for users, outline key considerations in developing an efficient pipeline to map an unprecedented number of connectomes, and report on the quality control procedures that were completed to ensure connectome reliability and accuracy. We demonstrate that our structural and functional connectivity matrices meet a number of quality control checks and replicate previously established findings in network neuroscience. We envisage that our resource will enable new studies of the human connectome in health, disease, and aging at an unprecedented scale.


HNK-1 in Morphological Study of Development of the Cardiac Conduction System in Selected Groups of Sauropsida.
Human natural killer (HNK)-1 antibody is an established marker of developing cardiac conduction system (CCS) in birds and mammals. In our search for the evolutionary origin of the CCS, we tested this antibody in a variety of sauropsid species (Crocodylus niloticus, Varanus indicus, Pogona vitticeps, Pantherophis guttatus, Eublepharis macularius, Gallus gallus, and Coturnix japonica). Hearts of different species were collected at various stages of embryonic development and studied to map immunoreactivity in cardiac tissues. We performed detection on alternating serial paraffin sections using immunohistochemistry for smooth muscle actin or sarcomeric actin as myocardial markers, and HNK-1 to visualize overall staining pattern and then positivity in specific myocyte populations. We observed HNK-1 expression of various intensity distributed in the extracellular matrix and mesenchymal cell surface of cardiac cushions in most of the examined hearts. Strong staining was found in the cardiac nerve fibers and ganglia in all species. The myocardium of the sinus venosus and the atrioventricular canal exhibited transitory patterns of expression. In the Pogona and Crocodylus hearts, as well as in the Gallus and Coturnix ones, additional expression was detected in a subset of myocytes of the (inter)ventricular septum. These results support the use of HNK-1 as a conserved marker of the CCS and suggest that there is a rudimentary CCS present in developing reptilian hearts. Anat Rec, 302:69-82, 2019. © 2018 Wiley Periodicals, Inc.


Self-oscillating polymer fueled by organic acid.
Here we report the biomimetic polymer that causes self-oscillation driven by the addition of biorelated organic acid. We constructed the built-in system where all of the substrates of the BZ reaction other than biorelated organic substrates were incorporated into the polymer chain. The quarternary copolymer, which includes both of the pH-control and oxidant-supplying sites in the poly(N-isopropylacrylamide-co-Ru(bpy)3) chain was synthesized. By using the polymer, we first succeeded in causing the self-oscillation of the polymer only in the coexistence of organic acid.


Exposure to persistent organic pollutants and thyroid cancer risk: a study protocol of systematic review and meta-analysis.
The thyroid cancer incidence has been increasing all over the world. However, the aetiology of thyroid cancer remains unclear. A growing body of evidence suggested exposure to persistent organic pollutants (POPs) may play a role in the initiation of thyroid cancer, but the results are generally inconsistent across studies. This review aims to synthesise the evidence for the health effects of POPs on the risk of thyroid cancer. This protocol was reported in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA) statements. A comprehensive search, including electronic database search (eg, PubMed, Embase, ProQuest and CNKI), website search and manual search, will be performed to identify all eligible studies. The Population, Exposure, Comparator and Outcome framework was used to clarify the inclusion and exclusion criteria. The Newcastle-Ottawa Scale will be used to assess the quality of included studies. Maximally adjusted effect estimates from individual studies will be summarised with random-effect models in a conservative manner. I2 statistics and Q-tests will be used to test the heterogeneity across studies. We will perform extensive sensitivity analyses, such as confounding risk ratio (confounding), E-value, fixed-effect models, excluding the most relatively weighted study, including only the high-quality studies and many predesigned subgroup analyses, etc. The findings will be reported in accordance to the PRISMA guidelines. Ethical approval is not required in this systematic review of published literatures. The results will be published in a peer-reviewed journal and presented at relevant conferences. CRD42020181343.


The minimum mass of detectable planets in protoplanetary discs and the derivation of planetary masses from high-resolution observations.
We investigate the minimum planet mass that produces observable signatures in infrared scattered light and submillimetre (submm) continuum images and demonstrate how these images can be used to measure planet masses to within a factor of about 2. To this end, we perform multi-fluid gas and dust simulations of discs containing low-mass planets, generating simulated observations at 1.65, 10 and 850 μm. We show that the minimum planet mass that produces a detectable signature is ∼15 M⊕: this value is strongly dependent on disc temperature and changes slightly with wavelength (favouring the submm). We also confirm previous results that there is a minimum planet mass of ∼20 M⊕ that produces a pressure maximum in the disc: only planets above this threshold mass generate a dust trap that can eventually create a hole in the submm dust. Below this mass, planets produce annular enhancements in dust outwards of the planet and a reduction in the vicinity of the planet. These features are in steady state and can be understood in terms of variations in the dust radial velocity, imposed by the perturbed gas pressure radial profile, analogous to a traffic jam. We also show how planet masses can be derived from structure in scattered light and submm images. We emphasize that simulations with dust need to be run over thousands of planetary orbits so as to allow the gas profile to achieve a steady state and caution against the estimation of planet masses using gas-only simulations.


Functional optoacoustic neuro-tomography of calcium fluxes in adult zebrafish brain in vivo.
Genetically-encoded calcium indicators (GECIs) have revolutionized neuroimaging by enabling mapping of the activity of entire neuronal populations in vivo. Visualization of these powerful activity sensors has to date been limited to depth-restricted microscopic studies due to intense light scattering in the brain. We demonstrate, for the first time, in vivo real-time volumetric optoacoustic monitoring of calcium transients in adult transgenic zebrafish expressing the GCaMP5G calcium indicator. Fast changes in optoacoustic traces associated with GCaMP5G activity were detectable in the presence of other strongly absorbing endogenous chromophores, such as hemoglobin. The new functional optoacoustic neuroimaging method can visualize neural activity at penetration depths and spatio-temporal resolution scales not covered with the existing neuroimaging techniques.


Diagnostic methods in planning palliation of spinal metastases.
In a prospective study of 30 patients with newly diagnosed spinal metastases the benefit of different imaging techniques in planning palliation was studied. Magnetic resonance imaging (MRI) was compared to scintigraphy, conventional radiography and computerized tomography (CT), prior to radiotherapy or surgery. In the first comparison, a total of 159 pathologic lesions could be evaluated. MRI was superior in the detection of suspect metastases compared to conventional radiography and scintigraphy (P less than 0.0001 and p less than 0.01, respectively). MRI also gave useful information about adjacent soft tissue components, vessels, nerves and spinal cord compression, i.e. useful information when planning stabilizing surgery. Both MRI and CT were sensitive and specific methods but when comparing 120 pathologic lesions the detection rate of MRI was significantly higher than that of CT (p less than 0.01). In conclusion, scintigraphy and conventional radiography are adequate enough if palliative radiotherapy is planned. When considering surgery MRI is advocated preoperatively for defining operability.


[Two cases of idiopathic carotid-cavernous fistula with headache and ophthalmoplegia].
We report two cases of idiopathic carotid-cavernous fistula (CCF) with primary symptoms of headache and diplopia. A 47-year-old woman presented with throbbing headache in her right frontal region followed by right trochlear nerve palsy. Brain magnetic resonance imaging (MRI) was normal but magnetic resonance angiography (MRA) and computed tomographic angiography (CTA) revealed abnormal signals around the right cavernous sinus. CCF was diagnosed by conventional angiography. The symptoms improved naturally but after about 1 year she suddenly exhibited conjunctival congestion. A 41-year-old man complained of fluctuating headache with sudden left abducens nerve palsy. MRI and MRA were normal but CTA showed abnormal signals around the left cavernous sinus. A final diagnosis of CCF was made by conventional angiography and he was transferred to another hospital for stereotactic radiosurgery. Diagnosis of CCF tends to be delayed in cases presenting with only headache and external ophthalmoplegia. However, CCF with cortical vein drainage can lead to cerebral hemorrhage and early correct diagnosis is needed. Our cases showed a dilated superior ophthalmic vein in enhanced CT and an abnormal signal around the cavernous sinus in CTA. Therefore, CTA may be useful as a relatively non-invasive method that can provide diagnostic clues for CCF.


Fatty Acid Diversity is Not Associated with Neutral Genetic Diversity in Native Populations of the Biodiesel Plant Jatropha curcas L.
Jatropha curcas L. (Euphorbiaceae) is a shrub native to Mexico and Central America, which produces seeds with a high oil content that can be converted to biodiesel. The genetic diversity of this plant has been widely studied, but it is not known whether the diversity of the seed oil chemical composition correlates with neutral genetic diversity. The total seed oil content, the diversity of profiles of fatty acids and phorbol esters were quantified, also, the genetic diversity obtained from simple sequence repeats was analyzed in native populations of J. curcas in Mexico. Using the fatty acids profiles, a discriminant analysis recognized three groups of individuals according to geographical origin. Bayesian assignment analysis revealed two genetic groups, while the genetic structure of the populations could not be explained by isolation-by-distance. Genetic and fatty acid profile data were not correlated based on Mantel test. Also, phorbol ester content and genetic diversity were not associated. Multiple linear regression analysis showed that total oil content was associated with altitude and seasonality of temperature. The content of unsaturated fatty acids was associated with altitude. Therefore, the cultivation planning of J. curcas should take into account chemical variation related to environmental factors.


Convection-enhanced delivery into the rat brainstem.
Convection-enhanced delivery (CED) can be used safely to achieve high local infusate concentrations within the brain and spinal cord. The use of CED in the brainstem has not been previously reported and may offer an alternative method for treating diffuse pontine gliomas. In the present study the authors tested CED within the rat brainstem to assess its safety and establish distribution parameters. Eighteen rats underwent stereotactic cannula placement into the pontine nucleus oralis without subsequent infusions. Twenty rats underwent stereotactic cannula placement followed by infusion of fluorescein isothiocyanate (FITC)-dextran at a constant rate (0.1 microl/minute) until various total volumes of infusion (V(i)s) were reached: 0.5, 1, 2, and 4 microl. Additional rats underwent FITC-dextran infusion (V, 4 microl) and were observed for 48 hours (five animals) or 14 days (five animals). Serial (20-microm thick) brain sections were imaged using confocal microscopy with ultraviolet illumination, and the volume of distribution (Vd) was calculated using computer image analysis. Histological analysis was performed on adjacent sections. No animal exhibited a postoperative neurological deficit, and there was no histological evidence of tissue disruption. The Vd increased linearly (range 15.4-55.8 mm3) along with increasing Vi, with statistically significant correlations for all groups that were compared (p < 0.022). The Va/Vi ratio ranged from 14 to 30.9. The maximum cross-sectional area of fluorescence (range 9.8-20.9 mm2) and the craniocaudal extent of fluorescence (range 2.8-5.1 mm) increased with increasing Vi. Convection-enhanced delivery can be safely applied to the rat brainstem with substantial and predictable V(d)s. This study provides the basis for investigating delivery of various candidate agents for the treatment of diffuse pontine gliomas.


Proposal of a New System for Essential Oil Classification Based on Low-Cost Gas Sensor and Machine Learning Techniques.
Essential oils are valuable in various industries, but their easy adulteration can cause adverse health effects. Electronic nasal sensors offer a solution for adulteration detection. This article proposes a new system for characterising essential oils based on low-cost sensor networks and machine learning techniques. The sensors used belong to the MQ family (MQ-2, MQ-3, MQ-4, MQ-5, MQ-6, MQ-7, and MQ-8). Six essential oils were used, including Cistus ladanifer, Pinus pinaster, and Cistus ladanifer oil adulterated with Pinus pinaster, Melaleuca alternifolia, tea tree, and red fruits. A total of up to 7100 measurements were included, with more than 118 h of measurements of 33 different parameters. These data were used to train and compare five machine learning algorithms: discriminant analysis, support vector machine, k-nearest neighbours, neural network, and naive Bayesian when the data were used individually or when hourly mean values were included. To evaluate the performance of the included machine learning algorithms, accuracy, precision, recall, and F1-score were considered. The study found that using k-nearest neighbours, accuracy, recall, F1-score, and precision values were 1, 0.99, 0.99, and 1, respectively. The accuracy reached 100% with k-nearest neighbours using only 2 parameters for averaged data or 15 parameters for individual data.


Clinical Response and Safety of Angiotensin Receptor and Neprilysin Inhibitor Combination in Advanced Chronic Kidney Disease and Heart Failure with Reduced Ejection Fraction.
Though the combination of an angiotensin receptor blocker (ARB) and a neprilysin inhibitor (ARNi) has been shown to be useful in heart failure with reduced ejection fraction (HFrEF), its use has mostly been restricted to chronic kidney disease (CKD) patients with an estimated glomerular filtration rate (eGFR) >30 mL/minute/1.73 m2 . We studied the role of ARNi in advanced CKD. Patients with HFrEF and advanced CKD with an eGFR of <30 mL/ minute/1.73 m2 were given ARNi (sacubitril with valsartan) and prospectively studied for changes in hospitalization rate for HF, clinical symptoms, levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP), eGFR, and potassium. Of 34 patients who received ARNi, five were excluded due to hyperkalemia and three due to a decrease in eGFR >30% occurring within 1 month. The remaining 26 patients included 17 with diabetes mellitus (DM) and 23 with underlying coronary artery disease. A total of eight patients had stage 4 and 18 stage 5 CKDs, amongst which eight required hemodialysis. Following ARNi, there was a significant decrease in the need for hospitalization for breathlessness (2.04 ± 1.03-0.23 ± 0.51; p < 0,05), New York Heart Association (NYHA) and Kansas City Cardiomyopathy Questionnaire (KCCQ) scores (3.77 ± 0.43-2.19 ± 0.56 and 28.58 ± 9.04-64.81 ± 14.3, respectively, p < 0.001) and NT-pro-BNP levels (24761 ± 12157.51-20149.92 ± 13555.269, p < 0.05) without significant change in eGFR after 6 months. There were no significant differences in the need for hospitalization, changes in NT proBNP levels and eGFR between stages 4 and 5. Neprilysin inhibitor (ARNi) is effective and can be used with care even in patients with CKD stages 4 and 5 having HFrEF with monitoring of eGFR and potassium.


Quantitative Ultrasound Measurement at the Hand Phalanges Does Not Reveal Skeletal Disturbances in Children With Bronchial Asthma: A Longitudinal Observation.
To assess the skeletal status in asthmatic children treated with inhaled corticosteroids in a longitudinal observation by quantitative ultrasound (US) measurement at the hand phalanges. Thirty-four children were studied prospectively. Quantitative US measurements were performed at baseline and after a mean ± SD of 2.35 ± 0.20 years. The obtained results were compared to age-, sex-, and body size-matched control participants selected from a database of previously examined healthy children. Individual changes in the amplitude-dependent speed of sound (Ad-SoS) during the follow-up period were also analyzed. The mean age of the asthmatic children was 10.6 ± 2.5 years. The mean Ad-SoS in the asthmatic children at baseline was 1940.5 ± 49.6 m/s, and the mean Z score was -0.26 ± 0.80. Corresponding values at the follow-up examination were 1976.2 ± 63.6 m/s and -0.18 ± 1.16. The results did not differ significantly in comparison to the healthy controls. The analysis of individual changes in Ad-SoS revealed that 18 participants had a significant increase in this parameter (ie, exceeding the least significant change threshold), and 16 did not have a significant change in their values. No one had a significant decrease in Ad-SoS. Quantitative US at the hand phalanges applied as a diagnostic tool revealed no essential differences in the pattern of skeletal development between asthmatic children treated with inhaled glucocorticosteroids and healthy controls.


Measures of Heart Rate Variability in 24-h ECGs Depend on Age but Not Gender of Healthy Children.
Many methods computing heart rate variability (HRV) have been applied in studies in children. Not all of these methods have a comprehensive physiological interpretation, and not all of studies are in agreement with the Task Force Standards on HRV from 1996, and the New Joint Position Statement on the advances of HRV from 2015. The study aim was to analyse HRV in the 24-h ECGs of healthy children by the Poincare plots and Lomb-Scargle periodograms, and to follow proper HRV recommendations. Additionally, we investigated the associations between age, children's sex and measured HRV indices. One hundred healthy children, aged 3-18 underwent 24-h ECG Holter monitoring. HRV was analyzed by the Poincaré plots and spectral by Lomb-Scargle periodograms of RR intervals. The Mann-Whitney test was used to compare sex differences in HRV, the van Elteren's test was used to correct for the age-gender interaction, and non-parametric Spearman correlation was applied to analyse the association between age and HRV indices. None of the HRV measures differed significantly between boys and girls. None of the HRV indices was modified by the age-gender interaction. There were statistically significant associations of age with measures of ultra-low (rho = 0.42; p < 0.0001), very low (rho = 0.35; p = 00004) and low (rho = 0.30; p = 0.0028) frequency powers, the ratio of the low to high frequency power (rho = 0.38; p = 0.0001), indices of long-term (SD2; rho = 0.37; p = 0.0002) and total (SDNN; rho = 0.33; p = 0.0008) HRV, and the contribution of the long-term HRV to total HRV (CL; rho = 0.32; p = 0.0012). In general, HRV parameters derived from the analyses of Poincaré plots and Lomb-Scargle periodograms appear not to be affected by gender, however, most of them increase with age in the 24-h ECG recordings in healthy children.