Thermal diffusivity of glass ionomer cement systems.
The thermal diffusivity has been measured for 10 glass ionomer and resin-based materials: three conventional (water-hardened) glass ionomer cements, two silver-reinforced glass ionomers, an experimental stainless steel-reinforced glass ionomer, three visible light-cured (VLC) glass ionomer-resin hybrid materials, and a VLC resin-based product developed for the same clinical uses as the hybrid materials. Cube-shaped specimens, c. 10 x 10 x 10 mm, initially at room temperature were immersed in mercury surrounded by an ice-water bath. From the experimental cooling curve a semi-log plot of relative temperature decrease vs. time yielded a straight line whose slope is proportional to the thermal diffusivity. The values ranged from 1.74-5.16 x 10(-3) cm2 s-1, and all of the materials tested would have adequate insulating properties provided normal clinical thickness levels for lining materials are maintained. It was found that the thermal diffusivities for the three metal-reinforced glass ionomers, where composition information is available, do not follow a rule of mixtures applied to the individual components.


Disrupted network cross talk, hippocampal dysfunction and hallucinations in schizophrenia.
Hallucinations characterize schizophrenia, with approximately 59% of patients reporting auditory hallucinations and 27% reporting visual hallucinations. Prior neuroimaging studies suggest that hallucinations are linked to disrupted communication across distributed (sensory, salience-monitoring and subcortical) networks. Yet, our understanding of the neurophysiological mechanisms that underlie auditory and visual hallucinations in schizophrenia remains limited. This study integrates two resting-state functional magnetic resonance imaging (fMRI) analysis methods - amplitudes of low-frequency fluctuations (ALFF) and functional network connectivity (FNC) - to explore the hypotheses that (1) abnormal FNC between salience and sensory (visual/auditory) networks underlies hallucinations in schizophrenia, and (2) disrupted hippocampal oscillations (as measured by hippocampal ALFF) beget changes in FNC linked to hallucinations. Our first hypothesis was supported by the finding that schizophrenia patients reporting hallucinations have higher FNC between the salience network and an associative auditory network relative to healthy controls. Hippocampal ALFF was negatively associated with FNC between primary auditory cortex and the salience network in healthy subjects, but was positively associated with FNC between these networks in patients reporting hallucinations. These findings provide indirect support favoring our second hypothesis. We suggest future studies integrate fMRI with electroencephalogram (EEG) and/or magnetoencephalogram (MEG) methods to directly probe the temporal relation between altered hippocampal oscillations and changes in cross-network functional communication.


The Effect of Freeze-Drying Pretreatment on the Accuracy of Near Infrared Spectroscopic Food Analysis to Predict the Nutritive Values of Japanese Cooked Foods.
The official testing methods for establishing nutritive values are accurate but relatively costly and time-consuming. Near infrared spectroscopy (NIRS) is potentially an alternative method that can analyze several components in a few minutes using an exclusively electronic instrument with no need for a laboratory expert. However, the accuracy of commercial NIRS spectroscopic food analyzers is not sufficient for Japanese food labeling, because of interference from moisture contained in the foods. This study aims to assess the effect of a freeze-drying pretreatment on the accuracy of NIRS food analysis. Thirty-four samples, consisting of six food items habitually consumed in Japan and cooked by different cooking methods were treated by milling then freeze-drying. They were analyzed by a commercial NIRS instrument (Calorie AnswerTM) with calibration curves developed based on other freeze-dried samples. The obtained nutritive values (energy, protein, lipid, carbohydrate and moisture) were corrected to the values before freeze-drying using the vaporized moisture content. The same samples before freeze-drying were also analyzed using the official testing methods to assess the analytical accuracy using NIRS after freeze-drying, and further analyzed using the same NIRS with the commercial calibration curves to assess the effect of freeze-drying. The accuracies were better for the freeze-dried samples than for the wet samples. The magnitude of the error in energy and carbohydrate was significantly associated with the retained moisture content in the freeze-dried sample. In conclusion, freeze-drying was an effective pretreatment for improving the accuracy of NIRS analyses of Japanese cooked foods, although it is still time-consuming and needs additional investment.


Origin of Excitation Dependent Fluorescence in Carbon Nanodots.
The fascinating aspect of excitation dependent fluorescence in carbon nanodots has led to several hypotheses, starting from particle size distribution to the presence of different emissive states and even to sluggish solvent relaxation around nanodot. In this contribution we provide definitive evidence for the involvement of discrete multiple electronic states for the excitation dependent emission in carbon nanodots. The presence of different types of aggregates even at very dilute solutions used in ensemble fluorescence spectroscopy, where fluorescence intensity shows linear dependence with absorbance, is the origin of these multiple electronic states. Inhomogeneous broadening due to slow solvent relaxation leading to excitation dependent spectral shift has negligible influence in conventional solvents.


Systematic Characterization of Autophagy in Gestational Diabetes Mellitus.
Autophagy is a dynamic process that degrades and recycles cellular organelles and proteins to maintain cell homeostasis. Alterations in autophagy occur in various diseases; however, the role of autophagy in gestational diabetes mellitus (GDM) is unknown. In the present study, we characterized the roles and functions of autophagy in GDM patient samples and extravillous trophoblasts cultured with glucose. We found significantly enhanced autophagy in GDM patients. Moreover, high glucose levels enhanced autophagy and cell apoptosis, reducing proliferation and invasion, and these effects were ameliorated through knockdown of ATG5. Genome-wide 5-hydroxymethylcytosine data analysis further revealed the epigenomic regulatory circuitry underlying the induced autophagy and apoptosis in GDM and preeclampsia. Finally, RNA sequencing was performed to identify gene expression changes and critical signaling pathways after silencing of ATG5. Our study has demonstrated the substantial functions of autophagy in GDM and provides potential therapeutic targets for the treatment of GDM patients.


Synthesis, kinetics and pharmacological evaluation of mefenamic acid mutual prodrug.
A novel mutual prodrug (MA-P) consisting of mefenamic acid (MA) and paracetamol (P) has been synthesized as a gastrosparing NSAID, devoid of ulcerogenic side effects. The structure of synthesized drug was confirmed by elemental analysis, infrared spectroscopy, 1H NMR spectroscopy and mass spectrometry.The kinetics of ester hydrolysis was studied by HPLC at pH 2, pH 7.4 as well as in human plasma. The pharmacological activities (anti-inflammatory, analgesic and ulcerogenic) were evaluated for the synthesized drug. The ulcerogenic reduction in terms of gastric wall mucosa, hexosamine and total proteins were also measured in glandular stomach of rats. The results indicated that MA-P ester has better ulcer index than the parent drug.


Selective regulation of chemotactic lymphokine production. I. Selective potentiation of eosinophil chemotactic lymphokine production in alum hydroxy gel- and Bordetella pertussis vaccine-treated guinea pigs.
Delayed tissue eosinophilia in DNP-ovalbumin-induced allergic inflammatory skin lesions of guinea pigs was markedly enhanced by previous treatment with alum hydroxy gel (Alum) or Bordetella pertussis vaccine. This enhancement seemed due to increased production of a lymphocyte-derived eosinophil chemotactic factor (ECF) at the skin site. Treatment of animals with Alum potentiated antigen-induced in vitro ECF production by lymphoid cells from spleen and mesenteric lymph node of sensitized animals. The co-culture supernatants of lymphoid cells from Alum-treated animals also potentiated concanavalin A (Con A)-induced in vitro ECF production. The potentiating effect of Alum on ECF production seemed to be ascribed to the release of soluble factors from macrophages of the Alum-treated animals. The macrophage-derived soluble factor ECF-potentiating factor (ECF-PF) selectively potentiated ECF production but not macrophage chemotactic lymphokine production by Con A-stimulated lymphoid cells from normal animals. ECF-PF activity was associated with two separate m.w. fractions: one was 50,000 to 70,000 and the other was 10,000 to 20,000. The present study provides one of the explanations for enhanced ECF production by adjuvants, such as Alum and Bordetella pertussis vaccine.


Public health concerns about Tuberculosis caused by Russia/Ukraine conflict.
According to WHO, Ukraine has the fourth-highest Tuberculosis (TB) incidence in the WHO European region while globally has the fifth-highest number of confirmed cases of extensively drug-resistant TB. Before the Russian invasion in Ukraine several interventions have been employed to mitigate the TB epidemic in the country. However, the ongoing war has demolished meticulous efforts and subsequently worsen the situation. WHO in collaboration with the Ukraine government and other organizations such as EU and UK are required to take up arms against the situation. In this work, implications brought up from the war, efforts, and recommendations to battling TB epidemic due to the war are highlighted.


Biliary cryptosporidiosis in HIV-infected people after the waterborne outbreak of cryptosporidiosis in Milwaukee.
In March 1993, the municipal water supply in Milwaukee became contaminated with cryptosporidium and a widespread outbreak of cryptosporidiosis occurred. We retrospectively studied the relations among the clinical presentation, CD4 count, and survival in a group of 82 patients infected with the human immunodeficiency virus (HIV) in whom cryptosporidiosis developed during the outbreak. Infection was documented by the finding of cryptosporidium in stool. There was a sharp increase in the number of HIV-infected patients with cryptosporidiosis after the period of water contamination. Four of 24 patients with biliary symptoms (17 percent) and 30 of 58 without biliary symptoms (52 percent) were alive one year after the outbreak (P = 0.003). Twenty-one of the patients with biliary symptoms had CD4 counts < or = 50 per cubic millimeter, as compared with 36 of 57 patients without biliary symptoms (88 percent vs. 63 percent, P = 0.03). The CD4 count was not available for one patient in the latter group. Within one year, 41 of the patients with CD4 counts < or = 50 per cubic millimeter had died, as compared with 6 of those with higher counts (72 percent vs. 25 percent, P < 0.001). After adjustment for the CD4 count, independent predictors of death were older age and the presence of nausea and vomiting. When HIV-infected patients are exposed to cryptosporidium, those with CD4 counts < or = 50 per cubic millimeter are at increased risk for biliary symptoms and for death within one year after the infection.


ESGAR consensus statement on liver MR imaging and clinical use of liver-specific contrast agents.
To develop a consensus and provide updated recommendations on liver MR imaging and the clinical use of liver-specific contrast agents. The European Society of Gastrointestinal and Abdominal Radiology (ESGAR) formed a multinational European panel of experts, selected on the basis of a literature review and their leadership in the field of liver MR imaging. A modified Delphi process was adopted to draft a list of statements. Descriptive and Cronbach's statistics were used to rate levels of agreement and internal reliability of the consensus. Three Delphi rounds were conducted and 76 statements composed on MR technique (n = 17), clinical application of liver-specific contrast agents in benign, focal liver lesions (n = 7), malignant liver lesions in non-cirrhotic (n = 9) and in cirrhotic patients (n = 18), diffuse and vascular liver diseases (n = 12), and bile ducts (n = 13). The overall mean score of agreement was 4.84 (SD ±0.17). Full consensus was reached in 22 % of all statements in all working groups, with no full consensus reached on diffuse and vascular diseases. The consensus provided updated recommendations on the methodology, and clinical indications, of MRI with liver specific contrast agents in the study of liver diseases. • Liver-specific contrast agents are recommended in MRI of the liver. • The hepatobiliary phase improves the detection and characterization of hepatocellular lesions. • Liver-specific contrast agents can improve the detection of HCC.


Estimating directed brain-brain and brain-heart connectivity through globally conditioned Granger causality approaches.
While a large body of research has focused on the study of within-brain physiological networks (i.e. brain connectivity) as well as their disease-related aberration, few investigators have focused on estimating the directionality of these brain-brain interaction which, given the complexity of brain networks, should be properly conditioned in order to avoid the high number of false positives commonly encountered when using bivariate approaches to brain connectivity estimation. Additionally, the constituents of a number of brain subnetworks, and in particular of the central autonomic network (CAN), are still not completely determined. In this study we present and validate a global conditioning approach to reconstructing directed networks using complex synthetic networks of nonlinear oscillators. We then employ our framework, along with a probabilistic model for heartbeat generation, to characterize the directed functional connectome of the human brain and to establish which parts of this connectome effect the directed central modulation of peripheral autonomic cardiovascular control. We demonstrate the effectiveness of our conditioning approach and unveil a top-down directed influence of the default mode network on the salience network, which in turn is seen to be the strongest modulator of directed autonomic cardiovascular control.


Making the cut: the chemical biology of cytokinesis.
Cytokinesis is the last step in the cell cycle, where daughter cells finally separate. It is precisely regulated in both time and space to ensure that each daughter cell receives an equal share of DNA and other cellular materials. Chemical biology approaches have been used very successfully to study the mechanism of cytokinesis. In this review, we discuss the use of small molecule probes to perturb cytokinesis, as well as the role naturally occurring small molecule metabolites such as lipids play during cytokinesis.


Posttraumatic stress disorder and mild brain injury: controversies, causes and consequences.
Posttraumatic stress disorder (PTSD) is an anxiety condition that often arises following a traumatic experience. It has commonly been argued that impaired consciousness associated with mild brain injury (MBI) precludes encoding of the traumatic experience, and this prevents PTSD development. This review considers the available evidence on PTSD following MBI and indicates the distinctive nature of PTSD after MBI. The review then discusses the possible mechanisms that may mediate PTSD in this population. The interaction of PTSD and postconcussive symptoms is discussed within a cognitive model that emphasizes the role of catastrophic interpretations of postconcussive symptoms. Finally, the implications of PTSD after MBI for assessment and treatment are reviewed.


First Synthesis of an Oridonin-Conjugated Iridium(III) Complex for the Intracellular Tracking of NF-κB in Living Cells.
NF-κB is a critical transcription factor that plays an important role in mediating inflammation, the immune response, and cell proliferation. The activation of NF-κB leads to an enhancement of proinflammatory mediator expression, which is implicated in the pathogenesis of a variety of diseases. Therefore, methods that allow the intracellular tracking of NF-κB are particularly attractive because they can provide information regarding the pathways or stimulation responses that are involved in the activation of NF-κB. In this work, we report a novel platform to track intracellular NF-κB by employing the conjugated iridium(III) complex 1, which was synthesized through the unique combination of a luminescent iridium(III) moiety with the natural product oridonin. Experiments conducted with p50 knockdown cells revealed that complex 1 could detect the p50 subunit of NF-κB in cellulo. Furthermore, complex 1 tracked NF-κB translocation induced by tumor necrosis factor-α (TNF-α) as a model stimulus, without affecting the translocation process itself. To the best of our knowledge, complex 1 is the first metal-based compound that has been reported to be capable of monitoring intracellular NF-κB in living cells.


Abnormal excretion of oestrogens in complicated pregnancies.
The tremendous interpatient variations that occur for oestrogen excretion during pregnancy are largely overcome by expressing results in terms of relative concentrations (i.e., as percent of total oestrogens excreted). Specimens of urine from 28 pregnant patients with a variety of complications were assayed for their oestrogen content by an "oestrogen profile" technique and the results thus expressed were compared with those from 20 normal pregnancies. Statistically significant changes are shown in the group of patients in the "above" normal range (normal range = normal mean +/- 3 X SE) for five oestrogens (oestrone, 2-hydroxyoestrone, 2-methoxyoestrone, 2-hydroxyoestradiol, and 2-hydroxyoestriol) and "below" the normal range for one oestrogen (oestriol). When the means of the oestrogen values for the different groups of patients were examined, two things became obvious; firstly, only patients with hypertension showed these changes, and secondly, two additional oestrogens (16-hydroxyoestrone and 16-epioestriol) were excreted in large amounts by the normotensive "high risk" patients. A comparison of the two methods of expressing oestrogen assay results is made quantitatively (as milligrams per day) versus relatively (as percent of total oestrogens excreted), and advantages and disadvantages of each are discussed.


iPSC reprogramming-mediated aneuploidy correction in autosomal trisomy syndromes.
Trisomy 21, 18, and 13 are the major autosomal aneuploidy disorders in humans. They are mostly derived from chromosome non-disjunction in maternal meiosis, and the extra trisomic chromosome can cause several congenital malformations. Various genes on the trisomic chromosomes are intricately involved in the development of disease, and fundamental treatments have not yet been established. However, chromosome therapy has been developed to correct the extra chromosome in cultured patient cells, and it was recently reported that during reprogramming into iPSCs, fibroblasts from a Down syndrome patient lost the extra chromosome 21 due to a phenomenon called trisomy-biased chromosome loss. To gain preliminary insights into the underlying mechanism of trisomy rescue during the early stages of reprogramming, we reprogrammed skin fibroblasts from patients with trisomy syndromes 21, 18, 13, and 9 to iPSC, and evaluated the genomes of the individual iPSC colonies by molecular cytogenetic techniques. We report the spontaneous correction from trisomy to disomy upon cell reprogramming in at least one cell line examined from each of the trisomy syndromes, and three possible combinations of chromosomes were selected in the isogenic trisomy-rescued iPSC clones. Single nucleotide polymorphism analysis showed that the trisomy-rescued clones exhibited either heterodisomy or segmental uniparental isodisomy, ruling out the possibility that two trisomic chromosomes were lost simultaneously and the remaining one was duplicated, suggesting instead that one trisomic chromosome was lost to generate disomic cells. These results demonstrated that trisomy rescue may be a phenomenon with random loss of the extra chromosome and subsequent selection for disomic iPSCs, which is analogous to the karyotype correction in early preimplantation embryos. Our finding is relevant for elucidating the mechanisms of autonomous karyotype correction and future application in basic and clinical research on aneuploidy disorders.


Improvement of the Properties of Direct-Current Magnetron-Sputtered Al-Doped ZnO Polycrystalline Films Containing Retained Ar Atoms Using 10-nm-Thick Buffer Layers.
The use of a 10-nm-thick buffer layer enabled tailoring of the characteristics, such as film deposition and structural and electrical properties, of magnetron-sputtered Al-doped ZnO (AZO) films containing unintentionally retained Ar atoms. The AZO films were deposited on glass substrates coated with the buffer layer via direct-current magnetron sputtering using Ar gas, a substrate temperature of 200 °C, and sintered AZO targets with an Al2O3 content of 2.0 wt %. The use of a Ga-doped ZnO film possessing a texture with a specific well-defined orientation as the buffer layer was very effective for improving the crystallographic orientation, reducing the residual stress, and improving the carrier transport of the AZO films. The residual compressive stress and in-grain carrier mobility were responsible for the retention of Ar atoms by the films, as observed using an electron probe microanalyzer.


[CT-angiography with a 16-row CT scanner for perioperative evaluation of the hepatic arteries].
To evaluate the efficiency of CT angiography (CTA) with 16-row MSCT compared with MR angiography (MRA) in analyzing the arterial anatomy in patients undergoing liver surgery. In 30 patients, MRA and CTA studies of the abdominal vessels were reviewed. CT parameters: slice thickness 3 mm; collimation 1.5; reconstruction interval 2 mm (Philips MX 8000 IDT); 120 ml contrast media (400 mg/ml) at a rate of 4 ml/sec; acquisition of arterial-phase scans. The anatomy of the hepatic artery was evaluated from axial and reconstructed maximum-intensity-projection (MIP) images ("Slab-Viewer", Philips). MR parameters: contrast-enhanced coronal FLASH-3D sequences; slice thickness 1.4 mm; TR 3.47, TE 1.3; 1.5 T scanner (Siemens Somatom). Image quality was rated with a scoring system. Contrast enhancement of the hepatic artery and the liver parenchyma was measured. The image quality of CTA was rated as excellent in 18 (MRA 5); good in 8 (MRA 22); satisfactory in 4 patients (MRA 3), and non-diagnostic in 0 patient (MRA 1). Compared to MRA, the image quality of CTA was better in 15/30 patients; equal for both in 13 and worse in 2 patients. CTA provided a better depiction of the segmental branches of the hepatic arteries in 15/30 patients and revealed important anatomic variations of the hepatic artery in 8/30 patients. These variations were not be seen in MRA: e. g., MRA missed a left gastric arterial supply to the left liver. The ratio of contrast enhancement in liver parenchyma and hepatic artery was 4.7 in CTA and 4.5 in MRA. CTA with multislice scanners delivers better image quality and depiction of the hepatic arteries than MRA. Thus, MRI of the hepatic arteries can be replaced by routine CT, which is already part of the preoperative evaluation for liver transplantation.


Impact of diabetes mellitus and cardiometabolic syndrome on the risk of Alzheimer's disease among postmenopausal women.
In spite of an increase in the incidence and prevalence of diabetes mellitus (DM) and Alzheimer's disease (AD) in the aging population worldwide, limited attention has been paid to their potential association. To investigate the association of DM and cardiometabolic syndrome (CMS, a precursor to DM) with risk of incident AD among postmenopausal women. Postmenopausal women aged 50-79 (n = 63117) who participated in the U.S. Women's Health Initiative Observational Study (WHIOS), recruited in 1993-1998, without baseline AD and followed up through March 1, 2019, were analyzed. AD was classified by participant-reported history of doctor-diagnosis of incident AD in the WHIOS. DM was defined by participant-report or treated because of diabetes or serum glucose concentrations ≥ 126 mg/dL. CMS was defined as having ≥ 3 of five CMS components: large waist circumference, high blood pressure, elevated triglycerides, elevated glucose, and low high-density lipoprotein cholesterol. The associations of DM and CMS with AD were analyzed using Cox's proportional hazards regression analysis. During a median follow-up of 20 years (range: 3.36 to 23.36 years), of 63117 participants, 8340 developed incident AD. Women with DM had significantly higher incidence of AD [8.5, 95% confidence interval (CI): 8.0-9.0 per 1000 person-years (PY)] than those without DM (7.1, 95%CI: 6.9-7.2 per 1000 PY). Multivariate Cox's regression analysis indicated that women with DM or CMS had a significantly higher risk of AD than those without DM or CMS. The corresponding hazard ratios [HR (95%CI)] were 1.22 (1.13-1.31, P < 0.001) in subjects with DM, and 1.18 (1.09-1.27, P < 0.001) in subjects with CMS. The HRs diminished with age and became non-significant in the oldest age group. During a median follow-up of 20 years, DM and CMS were significantly associated with the risk of AD among postmenopausal women. More specifically, women aged 50-69 with DM or CMS vs those without these conditions had significantly higher relative risks of AD than the relative risks of AD in those aged 70-79 with DM or CMS vs those without DM or CMS.


When Doctors Struggle: Current Stressors and Evaluation Recommendations for Physicians Contemplating Suicide.
The objective of this study was to document current risk factors associated with physicians' suicide ideation among a group of doctors enrolled in a Physician Health Program. A retrospective cohort study was drawn from administrative data. The study compared intake information between doctors who reported recent thoughts of suicide (n = 70) and those who did not (n = 1,572) using adjusted regression analysis. Current stressors included personal, financial, health, and occupational problems; ideation was more likely with multiple stressors. Physicians endorsing suicidal ideation lacked personal supports and scored differently on Short Form-36 measures. Evaluators treating physicians should assess enduring risks and current stressors, particularly multiple stressors, to help detect suicidal patients. Current stressors should not be viewed as transitory and it is critical to bring in collateral information.


Immunohistochemical expression of RANKL, RANK and OPG in gingival tissue of patients with periodontitis.
To evaluate the expression of the receptor activator of NF-κB (RANK), the receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG), in the gingival tissue of patients with periodontitis. Gingival tissue was obtained from 14 systemically healthy subjects with chronic periodontitis during conventional periodontal surgery. Immunohistochemistry was used to detect the expression of RANK, RANKL and OPG in the oral and periodontal pocket epithelium as well as in the connective tissue cells. RANKL was negatively expressed in both oral and periodontal pocket epithelium. OPG was also negative or weakly positive in the whole epithelium. RANK showed moderate/strong positive staining mainly in the basal and suprabasal layer of oral and periodontal pocket epithelium. In most of the cases, more than 60% of the inflammatory cell infiltrate stained for RANK and RANKL. In these cases the intensity of the stained cells ranged from moderate-to-strong. In less than half of the cases, OPG was positive in more than 60% of the stained cells of the inflammatory cell infiltrate. The RANK, RANKL and OPG proteins are differentially expressed in periodontal tissues and may play a major role in the bone loss occurring in periodontitis.


[The evaluation of the effect of venodilatation in 2 different systems of transdermal nitroglycerin release].
The aim of our study was to compare the activity of two different nitroglycerin controlled release systems (active matrix versus polyptychial matrix) on venous lower limbs circulation evaluated with strain-gauge plethysmography. Ten patients with stable coronary heart disease (M 5, F 5, mean age 65.1 +/- 4.6) were recruited and randomized to receive transdermal placebo and 5 or 10 mg of nitroglycerin carried by polyptychial or active matrix in a sequential and variable order. Five transdermal delivery systems were used with different content: placebo, nitroglycerin 5 or 10 mg on two different matrices (active matrix or polyptychial matrix). Venous strain-gauge plethysmography was performed in basal conditions and after 30, 60, 90, 120, 180, 240, 480, 1440 minutes, to evaluate the following parameters: maximal venous incremental volume at 40 and 60 mmHg (MVIV40 and MVIV60); time of maximal venous incremental volume at 60 mmHg (tMVIV60); maximal volume of outflow (MVO); time of maximal volume of outflow (tMVO); index of venous distensibility (dV/dP); index of venous tone (dP/dP); venous pressure (PV). Statistical data analysis was performed by one-way A.NO.VA and two-tailed Student's t test. The results of our study have shown that both transdermal systems, active and polyptychial matrix, are able to induce a venodilatation, but venodilatation induced by active matrix carried transdermal nitroglycerin along 24 hours is more stable and higher than that induced by polyptychial matrix carried transdermal nitroglycerin.


Dementia Patient Segmentation Using EMR Data Visualization: A Design Study.
(1) Background: The Electronic Medical Record system, which is a digital medical record management architecture, is critical for reliable medical research. It facilitates the investigation of disease patterns and efficient treatment via collaboration with data scientists. (2) Methods: In this study, we present multidimensional visual tools for the analysis of multidimensional datasets via a combination of 3-dimensional radial coordinate visualization (3D RadVis) and many-objective optimization (e.g., Parallel Coordinates). Also, we propose a user-driven research design to facilitate visualization. We followed a design process to (1) understand the demands of domain experts, (2) define the problems based on relevant works, (3) design visualization, (4) implement visualization, and (5) enable qualitative evaluation by domain experts. (3) Results: This study provides clinical insight into dementia based on EMR data via visual analysis. Results of a case study based on questionnaires surveying daily living activities indicated that daily behaviors influenced the progression of dementia. (4) Conclusions: This study provides a visual analytical tool to support cluster segmentation. Using this tool, we segmented dementia patients into clusters and interpreted the behavioral patterns of each group. This study contributes to biomedical data interpretation based on a visual approach.


Thioether S-ligation in a side-on micro-eta2:eta2-peroxodicopperii complex.
[(ANS)Cu(I)(CH(3)CN)](+) reacts with O(2) giving [{(ANS)Cu(II)}(2)(micro-eta(2):eta(2)-O(2)(2-))](2+), nu(O-O) = 731 cm(-1), shown to possess S-thioether ligation, based on comparisons with analogues having all N-ligands or a -S(Ph) group. The finding is a rare occurrence and new for side-on O(2)(2-) binding.


[Analysis on Focus of Clinical Evaluation of Dental Implants (Systems)].
From the perspective of technical evaluation, this article introduces the focus of clinical evaluation of dental implants (systems) in comparison with the comparable devices and discusses the clinical evaluation of such products,combined with the clinical evaluation review of dental implants (systems) products in recent years, in order to provide reference for the registration of these products.


Performance and exhaust emission characteristics investigation of compression ignition engine fuelled with microalgae biodiesel and its diesel blends.
Biofuels extracted from plant biomass can be used as fuel in CI engines to lower a hazardous atmospheric pollutant and mitigate climate risks. Furthermore, its implementation is hampered by inevitable obstacles such as feedstocks and the crop area required for their cultivation, leading to a lack of agricultural land for the expansion of food yields. Despite this, microalgae have been discovered to be the most competent and unwavering source of biodiesel due to their distinguishing characteristics of being non-eatable and requiring no cropland for cultivation. The objectives of this paper was to look into the potential of a novel, formerly underappreciated biodiesel from microalgae species which could be used as a fuel substitute. Transesterification is being used to extract the biodiesel. Microalgae are blended with petroleum diesel in percentage to create microalgae blends (MAB) as needed for experimentation. The impact of biodiesel on performance as well as exhaust emission attributes of a 1-cylinder diesel engine was experimentally studied. Compared to petroleum diesel, different blend of microalgae biodiesel showed a decline in torque and hence brake power, resulting in an average fall of 7.14 % in brake thermal efficiency and 11.54 % increase in brake-specific fuel consumption. There were wide differences in exhaust emission characteristics, including carbon monoxide and hydrocarbon, as the blend ratio in diesel increased. Moreover, nitrogen oxides and carbon dioxides increase in all algae biodiesel blends, but they are still within the acceptable range of petroleum diesel.


[Value of double contrast-enhanced ultrasound QontraXt three-dimensional pseudocolor quantitative analysis to therapeutic effect evaluation of preoperative neoadjuvant chemotherapy in advanced gastric cancer patients].
Objective: To investigate the value of tumor perfusion parameter measured by using double contrast-enhanced ultrasound (DCEUS) QontraXt three-dimensional pseudocolor quantitative analysis to the therapeutic effect evaluation of preoperative neoadjuvant chemotherapy (NAC) in advanced gastric cancer (AGC) patients. Methods: Eighty-nine AGC patients underwent 3 cycles of preoperative NAC (XELOX) followed by complete resection of lesion. The DCEUS QontraXt three-dimensional pseudocolor was performed one or two weeks before the NAC and operation were applied, respectively. The peak enhancement (PE), time to peak (TP), sharpness of the bolus (β) and area under the enhancement curve (AUC) of primary gastric tumor were measured by QontraXt three-dimensional pseudocolor quantitative analysis. These DCEUS parameters between respond and non-respond groups before and after NAC therapy were compared. The prediction accuracy of DCEUS to the therapeutic effect evaluation of preoperative NAC was determined by the receive operating characteristic (ROC) curves. Results: Among 89 AGC patients, 52 patients responded to NAC therapy, while 37 patients resisted to NAC therapy. Twelve cases in respond group and 26 cases in non-respond group were mucinous carcinoma. Forty cases in respond group and 11 cases in non-respond group were non-mucinous carcinoma (P<0.05). In responder group, the PE and TP before NAC were (53.7±9.3)% and (14 521±2 667) ms, and (32.2±5.5)% and (17 235±1 898) ms after NAC. The ratio of changes of PE (ΔPE) and TP (ΔTP) were 0.43±0.17 and 0.36±0.14, respectively. In non-respond group, the PE and TP before NAC were (54.4±7.2)% and (13 869±3 247) ms, and (45.3±6.1)% and (15 127±1 423) ms after NAC therapy. The ratio of ΔPE and ΔTP were 0.24±0.20 and 0.22±0.12. The PE and TP after NAC, the ratio of ΔPE and ΔTP were significant different among these two groups (all of P<0.05). The ROC curves showed that the ratio of ΔPE in assessing the respond of gastric cancer patients to NAC was superior compared to other parameters (AUC=0.784, P=0.004). The optimal cut-off value of the ratio of ΔPE was 24% and its sensitivity and specificity to the therapeutic effect evaluation of NAC in gastric cancer were 82.7% and 64.9%. Conclusion: DCEUS QontraXt three-dimensional pseudocolor quantitative analysis might be a novel, noninvasive and reliable method to evaluate the therapeutic effect of preoperative NAC in AGC patients.


Neutron diffraction study of liquid N-methylformamide using EPSR simulation.
The structure of N-methylformamide (NMF) in liquid state has been investigated using a combination of neutron diffraction measurements augmented with isotopic substitution and empirical potential structure refinement computer simulations. The reference potential used was optimized previously and consisted of Coulomb and 6-12 Lennard-Jones interactions for the atoms. The results show that the three-dimensional model of the liquid structure constructed at the correct atomic number density is consistent with the diffraction experimental data. The liquid structure is orientated by the hydrogen bonds among the molecules. Each NMF molecule is, on average, hydrogen bonded to two others. The findings indicate that dimers and "linear" trimers are very stable species in the liquid bulk. Because of that, the liquid is strongly structured into a chain-like structure. Neighboring chains are stabilized with respect to each other by weak O...H(C) hydrogen bonds. The results are consistent with the known physicochemical properties of the liquid.


Context differences reveal insulator and activator functions of a Su(Hw) binding region.
Insulators are DNA elements that divide chromosomes into independent transcriptional domains. The Drosophila genome contains hundreds of binding sites for the Suppressor of Hairy-wing [Su(Hw)] insulator protein, corresponding to locations of the retroviral gypsy insulator and non-gypsy binding regions (BRs). The first non-gypsy BR identified, 1A-2, resides in cytological region 1A. Using a quantitative transgene system, we show that 1A-2 is a composite insulator containing enhancer blocking and facilitator elements. We discovered that 1A-2 separates the yellow (y) gene from a previously unannotated, non-coding RNA gene, named yar for y-achaete (ac) intergenic RNA. The role of 1A-2 was elucidated using homologous recombination to excise these sequences from the natural location, representing the first deletion of any Su(Hw) BR in the genome. Loss of 1A-2 reduced yar RNA accumulation, without affecting mRNA levels from the neighboring y and ac genes. These data indicate that within the 1A region, 1A-2 acts an activator of yar transcription. Taken together, these studies reveal that the properties of 1A-2 are context-dependent, as this element has both insulator and enhancer activities. These findings imply that the function of non-gypsy Su(Hw) BRs depends on the genomic environment, predicting that Su(Hw) BRs represent a diverse collection of genomic regulatory elements.


G6PD--an old bottle with new wine.
The major role of glucose-6-phosphate dehydrogenase (G6PD) is to generate reduced nicotinamide adenine dinucleotide phosphate (NADPH), which is indispensable to reductive metabolism and maintenance of cellular redox homeostasis. Most advances in this field have been made in the pathophysiology of G6PD-deficient erythrocytes and the molecular characterization of different G6PD variants. Recently, numerous studies have shown the importance of G6PD in cell growth, development and disease progression.


Antibody Isotypes for Tumor Immunotherapy.
Compared to the evolutionary diversity of antibody isotypes, the spectrum of currently approved therapeutic antibodies is biased to the human IgG1 isotype. Detailed studies into the different structures and functions of human isotypes have suggested that other isotypes than IgG1 may be advantageous for specific indications - depending on the complex interplay between the targeted antigen or epitope, the desired mode of action, the pharmacokinetic properties, and the biopharmaceutical considerations. Thus, it may be speculated that with the increasing number of antibodies becoming available against a broadening spectrum of target antigens, identification of the optimal antibody isotype for particular therapeutic applications may become critical for the therapeutic success of individual antibodies. Thus, investments into this rather unexplored area of antibody immunotherapy may provide opportunities for distinction in the increasingly busy 'antibody space'. Therefore, IgG, IgA, IgE as well as IgM isotypes will be discussed in this review.


[Effect of Ebosin on the inflammatory cytokines in THP-1 cells].
Ebosin is a novel exopolysaccharide produced by Streptomyces sp.139 with remarkable activity against rheumatic arthritis in vivo. In this paper, we reported effects of Ebosin on the inflammatory cytokines including interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFalpha) in THP-1 cells. With the special fluorogenic peptide as substrates, the enzymatic activities of interleukin-1beta converting enzyme (ICE) and TNFalpha-converting enzyme (TACE) were inhibited by Ebosin separately. Using the real-time reverse transcription polymerase chain reaction (real-time PCR), the mRNA synthesis of the three cytokines were identified decline separately by Ebosin. The secretion quantum of three cytokines in THP-1 cells with Ebosin was lower than that of normal THP-1 cells determined by ELISA assay and Western blotting. All of these results showed that Ebosin has remarkably suppressed synthesis of the three cytokines in THP-1 cells through different pathways. The primary study of Ebosin on anti-inflammation mechanism was promoted developing the new drugs treating rheumatic arthritis.


Interleukin-4 and interleukin-13 differentially regulate epithelial chloride secretion.
Intestinal epithelia are in intimate contact with subepithelial and intraepithelial lymphocytes. When stimulated, mucosal lymphocytes generate cytokines that act locally and influence functional aspects of many cell types. We have previously defined functional epithelial receptors for interferon-gamma, interleukin (IL)-4, and a recently described IL-4-like cytokine IL-13. In this study, we examine the ion transport properties of T84 cells, a crypt-like epithelial cell line, following exposure to IL-4 and IL-13. Basolateral exposure of epithelial monolayers to both IL-4 and IL-13 attenuated epithelial barrier function and increased paracellular flux of a dextran marker by greater than 65% in a dose- and time-dependent fashion. Stimulated Cl- secretion, as measured by epithelial short circuit current, however, was diminished only by IL-4 and not IL-13, demonstrating cytokine specificity in this epithelial function. Decreased Cl- secretion following IL-4 exposure was associated with diminished Cl- channel activity and IL-4 pretreatment of epithelia decreased expression of the cystic fibrosis transmembrane regulator. Finally, stimulated fluid transport across cultured epithelia was diminished following exposure to IL-4, but not IL-13. These results indicate that while post-receptor signaling events induced by IL-13 and IL-4 may be similar, end point function is cytokine-specific.


Estimation of diversity and combining abilities in Helianthus annuus L. under water stress and normal conditions.
Sunflower cannot produce high yields under water-limiting conditions. The aim of the present study was to prevent the impediments on yield and to develop varieties with high-yield potential under water scarce conditions. For achieving this objective, it is necessary to detect parents with desirable traits that mainly depend on the action of genes controlling the trait under improvement, combining ability, and genetic makeup of the parents. Heterosis can also be used to pool the desirable genes from genetically divergent varieties and these divergent parents could be detected by molecular studies. Ten tolerant and five susceptible tester lines were selected, crossed, and tested for genetic diversity using simple sequence repeat primers. We identified two parents (A-10.8 and G-60) that showed maximum (46.7%) genetic dissimilarity. On an average 3.1 alleles per locus were detected for twenty pair of primers. Evaluation of mean values revealed that under stress conditions the mean performances of the genotypes were reduced for all traits under study. Parent A-10.8 was consistent as a good general combiner for achene yield per plant under both non-stress and stress conditions. Line A-10.8 in the hybrid A-10.8 x G-60 proved to be a good combiner as it showed negative specific combining ability (SCA) effects for plant height and internodal length and positive SCA effects for head weight, achene yield per plant, and membrane stability index. Valuable information on gene action, combining ability, and heterosis was generated, which could be used in further breeding programs.


Subjective quantification of earplug occlusion effect using external acoustical excitation of the mouth cavity.
Occlusion of the ear canal by hearing aids or hearing protectors often results in an occlusion effect, which creates a discomfort to wearers in that it changes their perception of their own voice. As no account was found in the literature on the quantification of this subjective voice occlusion effect, an experimental method is proposed based on the use of an artificial sound source emitting within the subject's mouth to replace his own voice. A block diagram is constructed to identify the different internal sound path components involved in the perception of one's own voice and is used to show that the subjective voice occlusion effect is the weighted energy summation of two components. The first component, the voice air and body conduction occlusion effect for which data is obtained from the experiments reported in the present paper, constitute the lower limit of the subjective voice occlusion effect. The second component, the voice body conduction occlusion effect for which data is available in the literature, constitutes the upper limit. From these limits, order of magnitudes for subjective voice occlusion effect intervals are estimated to be [+5+20] dB below 2000 Hz and [-10+5] dB above 2000 Hz.


Residual symptoms in depression.
Despite successful response to therapy, subsyndromal depressive symptoms appear to be the rule in unipolar depression. Residual symptoms are present in more than 30% of patients who respond to antidepressants, specifically in subjects with more severe initial illness. The most prevalent residual symptoms are affective, somatic, cognitive and sleep disturbance. It has been shown that such persistent symptoms are associated with a higher risk of relapse, chronicity and functional impairment; associated with neuroanatomical changes. It is important to consider the possibility of persistence subthreshold symptoms and look for new therapeutic strategies for improving the level of remission in the treatment of major depressive disorder.


Sagittal abdominal diameter as a screening tool in clinical research: cutoffs for cardiometabolic risk.
Background. Waist girth and BMI are commonly used as markers of cardiometabolic risk. Accumulating data however suggest that sagittal abdominal diameter (SAD) or "abdominal height" may be a better marker of intra-abdominal adiposity and cardiometabolic risk. We aimed to identify cutoffs for SAD using a cardiometabolic risk score. Design. A population-based cross-sectional study. Methods. In 4032 subjects (1936 men and 2096 women) at age 60, different anthropometric variables (SAD, BMI, waist girth, and waist-to-hip ratio) were measured and cardiometabolic risk score calculated. ROC curves were used to assess cutoffs. Results. Among men SAD showed the strongest correlations to the majority of the individual risk factors; whereas in women SAD was equal to that of waist girth. In the whole sample, the area under the ROC curve was highest for SAD. The optimal SAD cutoff for an elevated cardiometabolic risk score in men was approximately 22 cm (95%CI; 21.6 to 22.8) and in women approximately 20 cm (95%CI; 19.4 to 20.8). These cutoffs were similar if the Framingham risk score was used. Conclusions. These cutoffs may be used in research and screening to identify "metabolically obese" men who would benefit from lifestyle and pharmacological interventions. These results need to be verified in younger age groups.


Menopause: life event or medical disease?
Women throughout the world experience menopause, but it is often difficult to determine what it means and how it is perceived by women. A dilemma exists as to whether menopause should be medicalized or treated as a normal life event. The effects of this decision on the woman and the role of the advanced practice nurse in assisting the woman through this time of change are presented.


Developmental exposure to 50 parts-per-billion arsenic influences histone modifications and associated epigenetic machinery in a region- and sex-specific manner in the adult mouse brain.
Epidemiological studies report that arsenic exposure via drinking water adversely impacts cognitive development in children and, in adults, can lead to greater psychiatric disease susceptibility, among other conditions. While it is known that arsenic toxicity has a profound effect on the epigenetic landscape, very few studies have investigated its effects on chromatin architecture in the brain. We have previously demonstrated that exposure to a low level of arsenic (50ppb) during all three trimesters of fetal/neonatal development induces deficits in adult hippocampal neurogenesis in the dentate gyrus (DG), depressive-like symptoms, and alterations in gene expression in the adult mouse brain. As epigenetic processes control these outcomes, here we assess the impact of our developmental arsenic exposure (DAE) paradigm on global histone posttranslational modifications and associated chromatin-modifying proteins in the dentate gyrus and frontal cortex (FC) of adult male and female mice. DAE influenced histone 3K4 trimethylation with increased levels in the male DG and FC and decreased levels in the female DG (no change in female FC). The histone methyltransferase MLL exhibited a similar sex- and region-specific expression profile as H3K4me3 levels, while histone demethylase KDM5B expression trended in the opposite direction. DAE increased histone 3K9 acetylation levels in the male DG along with histone acetyltransferase (HAT) expression of GCN5 and decreased H3K9ac levels in the male FC along with decreased HAT expression of GCN5 and PCAF. DAE decreased expression of histone deacetylase enzymes HDAC1 and HDAC2, which were concurrent with increased H3K9ac levels but only in the female DG. Levels of H3 and H3K9me3 were not influenced by DAE in either brain region of either sex. These findings suggest that exposure to a low, environmentally relevant level of arsenic during development leads to long-lasting changes in histone methylation and acetylation in the adult brain due to aberrant expression of epigenetic machinery based on region and sex.


AtFer4 ferritin is a determinant of iron homeostasis in Arabidopsis thaliana heterotrophic cells.
In plants, the iron storage protein ferritin can be targeted to both chloroplasts and mitochondria. To investigate the role of Arabidopsis ATFER4 ferritin in mitochondrial iron trafficking, atfer4-1 and atfer4-2 mutant knock-outs for the AtFer4 gene were grown in heterotrophic suspension cultures. Both mutants showed altered cell size and morphology, reduced viability, higher H₂O₂ content and reduced O₂ consumption rates when compared to wt. Although no reduction in total ferritin or in mitochondrial ferritin was observed in atfer4 mutants, total iron content increased in atfer4 cells and in atfer4 mitochondria. Transcript correlation analysis highlighted a partial inverse relationship between the transcript levels of the mitochondrial ferric reductase oxidase FRO3, putatively involved in mitochondrial iron import/export, and AtFer4. Consistent with this, FRO3 transcript levels were higher in atfer4 cells. We propose that the complex molecular network maintaining Fe cellular homeostasis requires, in Arabidopsis heterotrophic cells, a proper balance of the different ferritin isoforms, and that alteration of this equilibrium, such as that occurring in atfer4 mutants, is responsible for an altered Fe homeostasis resulting in a change of intraorganellar Fe trafficking.


Effect of dietary Polyphenon E and EGCG on lung tumorigenesis in A/J Mice.
To compare the chemopreventive efficacy of Polyphenon E (Poly E), (-)-epigallocatechin-3-gallate (EGCG) and Polyphenon E without EGCG (Poly E-EGCG) on the development of benzo(a)pyrene (B(a)P)-induced lung tumors in A/J mice. Female A/J mice were given a single intraperitoneal injection of B(a)P (100 mg/kg body weight). One week after B(a)P injection, animals received AIN-76A purified powder diet containing 0.975% (wt/wt) EGCG, 0.525% (wt/wt) Poly E-EGCG or 1.5% (wt/wt) Poly E for 24 weeks or control diet with no additives. Poly E treatment significantly decreased tumor multiplicity by 52% and tumor load by 64%, while EGCG and Poly E-EGCG did not significantly inhibit lung tumor multiplicity. EGCG was more stable in a complex mixture (Poly E) than as a pure compound. EGCG was ineffective when administered by diet likely due to its instability. Thus, EGCG's efficacy on mice lung tumorigenesis requires the presence of other tea catechins.


Built and social environments and overweight among Brazilian adults from medium-sized city: CUME Project.
A cross-sectional study enrolled participants from the CUME project (n = 289) who lived in Viçosa, Brazil. The neighborhood unit adopted was the buffer (200 meters), considering the participant's residence as central point. We measure the number of public and private facilities inside the buffer as well as violent criminal occurrences. Food establishments were categorized into establishments with predominant sale of natural or minimally processed foods, mixed establishments, and establishments with predominant sale of ultra-processed foods. Those who attended the face-to-face interview filled two scales of perception of the environment. Overall, 33.6% of participants reported overweight. We observed a higher concentration of individuals close to the central region of the city. Access to different establishments, food environments, and criminal occurrences differed between normal-weight and overweight individuals. The groups deferred in the perception of the location of squares, open public spaces, clubs, and soccer fields. The results indicate the association between environmental characteristics and overweight in Brazilian adults.


Infection dynamics of highly pathogenic avian influenza and virulent avian paramyxovirus type 1 viruses in chickens, turkeys and ducks.
A range of virus doses were used to infect 3-week-old chickens, turkeys and ducks intranasally/intraocularly, and infection was confirmed by the detection of virus shedding from the buccal or cloacal route by analysis of swabs collected using real-time reverse transcriptase-polymerase chain reaction assays. The median infectious dose (ID(50)) and the median lethal dose (LD(50)) values for two highly pathogenic avian influenza (HPAI) viruses of H5N1 and H7N1 subtypes and one virulent Newcastle disease virus (NDV) were determined for each virus and host combination. For both HPAI viruses, turkeys were >100-fold more susceptible to infection than chickens, while both these hosts were >10-fold more susceptible to H5N1 virus than the H7N1 virus. All infected chickens and turkeys died. Ducks were also much more readily infected with the H5N1 virus (ID(50)< or =10(1) median embryo infective dose [EID(50)]) than the H7N1 virus (ID(50)=10(4.2) EID(50)). However, the most notable difference between the two viruses was their virulence for ducks, with a LD(50) of 10(3) EID(50) for the H5N1 virus, but no deaths in ducks being attributed to infection with H7N1 virus even at the highest dose (10(6) EID(50)). For both HPAI virus infections of ducks, the ID(50) was lower than the LD(50), indicating that infected birds were able to survive and thus excrete virus over a longer period than chickens and turkeys. The NDV strain used did not appear to establish infection in ducks even at the highest dose used (10(6) EID(50)). Some turkeys challenged with 10(6) EID(50), but not other doses, of NDV excreted virus for a number of days (ID(50)=10(4.6) EID(50)), but none died. In marked contrast, chickens were shown to be extremely susceptible to infection and all infected chickens died (ID(50)/LD(50)=10(1.9) EID(50)).


Genetic crossovers are predicted accurately by the computed human recombination map.
Hotspots of meiotic recombination can change rapidly over time. This instability and the reported high level of inter-individual variation in meiotic recombination puts in question the accuracy of the calculated hotspot map, which is based on the summation of past genetic crossovers. To estimate the accuracy of the computed recombination rate map, we have mapped genetic crossovers to a median resolution of 70 Kb in 10 CEPH pedigrees. We then compared the positions of crossovers with the hotspots computed from HapMap data and performed extensive computer simulations to compare the observed distributions of crossovers with the distributions expected from the calculated recombination rate maps. Here we show that a population-averaged hotspot map computed from linkage disequilibrium data predicts well present-day genetic crossovers. We find that computed hotspot maps accurately estimate both the strength and the position of meiotic hotspots. An in-depth examination of not-predicted crossovers shows that they are preferentially located in regions where hotspots are found in other populations. In summary, we find that by combining several computed population-specific maps we can capture the variation in individual hotspots to generate a hotspot map that can predict almost all present-day genetic crossovers.


Trends in the incidence of acquired immunodeficiency syndrome-related malignancies in Thailand.
Thailand was one of the first Asian countries to be affected by the epidemic of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Furthermore, Thailand possesses a national cancer surveillance system based upon regional cancer registries. Data from five population-based cancer registries, covering one-fifth of the national population, were used to study trends in the incidence of malignancies related to HIV/AIDS in Thailand during the period 1989-2001. Although the incidence of Kaposi sarcoma (KS) increased slightly from 1989-1991 to 1995-1997, KS remains a very rare malignancy in Thailand compared with other countries in which the prevalence of HIV/AIDS is much lower. The authors reported a marked increase in the incidence of non-Hodgkin lymphoma (NHL), and particularly high-grade/diffuse NHL. However, the largest increases in incidence were noted among individuals age >/= 55 years and in regions with a relatively low prevalence of HIV/AIDS. The rarity of KS presumably reflected the low prevalence of the causative agent (i.e., KS-associated herpesvirus) in the Thai population. The increasing incidence of NHL may be related to the AIDS epidemic, although a similar increase is observed in many countries worldwide and is not specifically linked to the HIV/AIDS epidemic.


The effect of cholesterol-lowering agents on hepatic and plasma cholesterol in Niemann-Pick disease type C.
Niemann-Pick disease type C (NP-C) is a neurovisceral lipidosis characterized by defective intracellular trafficking of cholesterol and lysosomal accumulation of unesterified cholesterol, believed to be an offending metabolite. We studied the effect of cholesterol-lowering agents on hepatic and plasma cholesterol levels in NP-C by randomly assigning 25 patients with NP-C to one of five treatment regimens containing different combinations of cholestyramine, lovastatin, nicotinic acid, or dimethyl sulfoxide (DMSO). Unesterified cholesterol content was measured in liver biopsies before and after 4 months' treatment. All drug regimens except DMSO alone reduced hepatic and plasma cholesterol levels. Toxicity was limited and did not prevent any patient from completing the study. The combination of cholestyramine, lovastatin, and nicotinic acid lowered cholesterol levels in liver and blood with minimal side effects. A controlled clinical study will be necessary to determine if this regimen influences the rate of neurologic progression.


Sumanene Monolayer of Pure Carbon: A Two-Dimensional Kagome-Analogy Lattice with Desirable Band Gap, Ultrahigh Carrier Mobility, and Strong Exciton Binding Energy.
The design and synthesis of novel two-dimensional (2D) materials that possess robust structural stability and unusual physical properties may open up enormous opportunities for device and engineering applications. Herein, a 2D sumanene lattice that can be regarded as a derivative of the conventional Kagome lattice is proposed. The tight-binding analysis demonstrates sumanene lattice contains two sets of Dirac cones and two sets of flat bands near the Fermi surface, distinctively different from the Kagome lattice. Using first-principles calculations, two possible routines for the realization of stable 2D sumanene monolayers (named α phase and β phase) are theoretically suggested, and an α-sumanene monolayer can be experimentally synthesized with chemical vapor deposition using C21 H12 as a precursor. Small binding energies on Au(111) surface (e.g., -37.86 eV Å-2 for α phase) signify the possibility of their peel-off after growing on the noble metal substrate. Importantly, the GW plus Bethe-Salpeter equation calculations demonstrate both monolayers have moderate band gaps (1.94 eV for α) and ultrahigh carrier mobilities (3.4 × 104 cm2 V-1 s-1 for α). In particular, the α-sumanene monolayer possesses a strong exciton binding energy of 0.73 eV, suggesting potential applications in optics.


Augmentation of sodium butyrate-induced apoptosis by phosphatidylinositol 3'-kinase inhibition in the KM20 human colon cancer cell line.
We have recently shown that inhibition of the phosphatidylinositol3'-kinase (PI3k) pathway enhances sodium butyrate (NaBT)-mediated differentiation of human colon cancer cells. The purpose of this study was to determine whether PI3k inhibition can enhance the inhibitory effect of NaBT on an aggressive human colon cancer cell line, KM20. The KM20 cell line, established from a metastatic colon cancer, was treated in vitro with NaBT, gemcitabine, or 5-fluorouracil either alone or in combination with the PI3k inhibitors wortmannin or LY294002; DNA fragmentation and cell viability were measured. As further indicators of apoptosis, protein was extracted to determine caspase-9 and caspase-3 activation and cleavage of poly(ADP-ribose) polymerase. In addition, the effect of NaBT and wortmannin on in vivo KM20 tumor growth was determined. We demonstrate that inhibition of PI3k enhanced NaBT-mediated apoptosis and decreased KM20 cell viability; the nonspecific caspase inhibitor zVAD-fmk blocked the induction of apoptosis by the combination treatment. Either wortmannin or LY294002, combined with NaBT, enhanced activation of caspase-9 and caspase-3 and the subsequent cleavage of poly(ADP-ribose) polymerase. Furthermore, inhibition of PI3k increased the sensitivity of KM20 cells to gemcitabine and 5-fluorouracil. Wortmannin alone inhibited KM20 xenograft growth in vivo; the combination of wortmannin and NaBT demonstrated an enhanced effect compared with either agent alone. Our results are the first to show that inhibition of PI3k enhances NaBT-mediated colon cancer cell apoptosis through the activation of caspase-9 and caspase-3. Moreover, these findings suggest that agents that selectively target the PI3k pathway may enhance the effects of standard chemotherapeutic agents and provide novel adjuvant treatment for selected colon cancers.


Negative pressure ventilation: new uses for an old technique.
Negative pressure ventilation (NPV), a concept that was used in the 1940s through 1950s to support the victims of the polio epidemic, is regaining popularity. It is being used increasingly to intermittently support respiratory function in patients suffering from a variety of diseases. The use of NPV obviates the need for a surgically placed airway (if the patients' upper airway is intact) and allows the patient to resume many of his or her normal activities. Several types of NPV are available for use and experimentation, and it is strongly recommended that the appropriate type for each patient be chosen. Nursing care of the patient on NPV is essentially the same as that of any chronically ventilator-dependent patient. Issues unique to the patient supported on NPV include: increased potential for aspiration, skin breakdown around the NPV site, and "tank shock." Nursing plays an important role in identifying patients who may be candidates for NPV. Negative pressure ventilation may allow a formally hospital-bound patient the opportunity to be home with family and friends.


A novel somatodendritic marker defined by a peptide derived from the ALS2 protein.
We characterized an antibody raised against a peptide derived from the ALS2 protein, the product of a gene linked to recessive juvenile forms of amyotrophic lateral sclerosis, defining the ALS2 RLD-derived antigen (ARDA). In cultured rat cortical neurons, ARDA is localized in perikarya and neurites, but absent from nuclei. Double immunostaining of rodent cultured neurons and spinal cord sections for ARDA and MAP2, a marker of dendrites, or tau and phosphorylated neurofilaments, markers of axons, demonstrated that the ARDA antigen was localized in the somatodendritic compartment and excluded from axons. ARDA was also selectively localized to the somatodendritic compartment of motor neurons in human spinal cord. The ARDA antigen therefore represents a novel somatodendritic marker for embryonic and adult neurons.


Characterization of the glucose-induced lowering of sodium in mouse pancreatic beta-cells.
The mechanisms for glucose regulation of the sodium content of the pancreatic beta-cells were examined using aggregates of cells prepared from ob/ob-mice of a local colony. Exposure to glucose rapidly resulted in a protracted lowering of the sodium content as estimated with integrating flame photometry. Sodium became decreased after addition of 1 mmol l-1 glucose, and this effect was maximal with 5 mmol l-1 of the sugar. The effects of low glucose concentrations on the sodium content could not be mimicked by the poorly metabolized 3-o-methyl-D-glucose, and it disappeared in the presence of the metabolic inhibitor antimycin A. The significance of the Na/K pump for maintaining low sodium was illustrated by a substantial increase of the element in the presence of ouabain. However, there was no indication that glucose-induced lowering of sodium reflected activation of this pump when measuring the ouabain-sensitive uptake of 86Rb+. Neither bumetanide nor the bromo derivatives of cyclic AMP or cyclic GMP modified the glucose action on the sodium content. In evaluating whether the effect of glucose was mimicked by other inhibitors of the K+ permeability it was observed that 100 mumol l-1 quinine, but not tolbutamide, decreased sodium. It is concluded that the beta-cell is exceptional among excitable cells in responding to its natural physiological stimulant (glucose) by reduction of sodium. Acting in this way glucose facilitates the removal of Ca2+ from the cytoplasm.


Asp22 drives the protonation state of the Staphylococcus epidermidis glucose/H+ symporter.
The Staphylococcus epidermidis glucose/H+ symporter (GlcPSe) is a membrane transporter highly specific for glucose and a homolog of the human glucose transporters (GLUT, SLC2 family). Most GLUTs and their bacterial counterparts differ in the transport mechanism, adopting uniport and sugar/H+ symport, respectively. Unlike other bacterial GLUT homologs (for example, XylE), GlcPSe has a loose H+/sugar coupling. Asp22 is part of the proton-binding site of GlcPSe and crucial for the glucose/H+ co-transport mechanism. To determine how pH variations affect the proton site and the transporter, we performed surface-enhanced IR absorption spectroscopy on the immobilized GlcPSe We found that Asp22 has a pKa of 8.5 ± 0.1, a value consistent with that determined previously for glucose transport, confirming the central role of this residue for the transport mechanism of GlcPSe A neutral replacement of the negatively charged Asp22 led to positive charge displacements over the entire pH range, suggesting that the polarity change of the WT reflects the protonation state of Asp22 We expected that the substitution of the residue Ile105 for a serine, located within hydrogen-bonding distance to Asp22, would change the microenvironment, but the pKa of Asp22 corresponded to that of the WT. A167E mutation, selected in analogy to the XylE, introduced an additional protonatable site and perturbed the protonation state of Asp22, with the latter now exhibiting a pKa of 6.4. These studies confirm that Asp22 is the proton-binding residue in GlcPSe and show that charged residues in its vicinity affect the pKa of glucose/H+ symport.


CTRP3 alleviates myocardial ischemia/reperfusion injury in mice through activating LAMP1/JIP2/JNK pathway.
Myocardial ischemia reperfusion (I/R) injury is an important complication of myocardial infarction reperfusion therapy, and no effective treatment has been identified. Based on preexisting evidence, C1q/tumor necrosis factor-related protein 3 (CTRP3) has been reported to be closely associated with myocardial dysfunction. In this study, we found that CTRP3 was downregulated in acute coronary syndrome (ACS) patients and myocardial I/R mice. Silence of CTRP3 aggravated cardiac systolic function due to I/R of mice, while CTRP3 overexpression ameliorated cardiac function. Moreover, overexpression of CTRP3 improved I/R inhibitory effects on the levels of creatinine phosphokinase (CPK), lactate dehydrogenase (LDH) and cardiac troponin-I (cTn-I), myocardial infarction area, the intensity of the 3-nitrotyrosine (3-NT), apoptosis and protein levels of LAMP1, JNK-Interacting Protein-2 (JIP-2) and JNK, while these effects could be exacerbated by downregulation of CTRP3. Co-IP experiments could identify physical interactions between CTRP3 and lysosomal-associated membrane protein 1 (LAMP1) and Numb and JIP2. LAMP1 silence aggravated the inhibition effects of I/R on JIP2 and JNK protein expression, CPK, LDH and cTn-I levels and caspase-3 activity, while overexpression of LAMP1 recovered these inhibition effects of I/R. JNK inhibitor (SP600125) could reverse the inhibitory effects of CTRP3 overexpression on CPK, LDH, cTn-I, myocardial infarction, strong positive staining for 3-NT and apoptosis. These findings demonstrated that CTRP3 protected against injury caused by myocardial I/R through activating LAMP1/JIP2/JNK pathway to attenuate myocardial injury, improve left ventricular function, decrease myocardial infarction, and reduce myocardial apoptosis.


Recipient polyclonal B cell activation and immunoglobulin production induced by priming with a retroviral superantigen.
The superantigen vSAG-7 (or MIs 1a) is a membrane glycoprotein encoded by the endogenous retrovirus mouse mammary tumor virus 7 (MMTV-7) and is highly stimulatory for V beta 6/CD4+ T cells. Priming of adult MMTV-7-negative mice with vSAG-7-expressing cells initially results in the activation of the peripheral V beta 6/CD4+ T cell compartment and is followed by T cell tolerance to the superantigen. During the course of tolerance induction the number of recipient B lymphocytes increases in the lymph nodes, but not the spleen, of vSAG-7-primed recipients. These B cells also express increased levels of class II MHC and present passively acquired superantigen. In this study we asked if these effects on the host B cell compartment are followed by the production of immunoglobulin. Priming of MMTV-7-negative BALB/c or CB.17 mice with vSAG-7-expressing cells from DBA/2 mice induced increases of both IgM and IgG2a in the serum. Use of Igh congenic CB.17 (IgMb) mice as recipients of the vSAG-7-presenting cells from DBA/2 (IgMa) donors indicated that the IgM and IgG produced were entirely of host origin. Priming with vSAG-7 also amplified (four- to fivefold) the antibody-producing cell response induced to a suboptimal dose of sheep RBC. Priming with purified B cells from vSAG-7 donors resulted in recipient V beta 6/CD4+ T cell activation and increased numbers of recipient B cells in the lymph nodes, but did not induce immunoglobulin production. In contrast, priming with purified CD8+ T cells resulted in increased quantities of serum IgM but not vSAG-7-reactive T cell activation or increased numbers of recipient B cells in the lymph nodes. These results indicate that the T cell activation and increased B cell number with upregulated class II MHC expression initially observed following vSAG-7 priming of adult MMTV-7-negative recipients are not linked to the induction of the recipient-derived immunoglobulin production.


Innovation adoption: introducing I.V. patient controlled analgesia to the nursing workplace.
Technology in the nursing workplace is inevitable but what is not certain is how well these technologies will be initially accepted by nurses. One technological innovation that has appeared in some Canadian hospitals is IV Patient Controlled Analgesia (IV PCA), an innovative technique for pain management, employing the use of a computer-driven pump. Few nursing studies have examined the adoption of technological innovations. This qualitative study examines the incorporation of IV PCA to the nursing workplace and job-related factors that influenced it. A five-phase integration process was identified along with factors impacting on this process. Incorporating IV PCA into nursing practice involved the nurses' judgements of the influence of this innovation on the nurses' comfort with care delivery; the patient/nurse relationship; managing the technology; and the relationship with other health care professionals and patients' family/visitors. Anxiety accompanied the integration process, peaking as IV PCA was introduced to patient care. Findings of this study suggest that actions and decisions initiated by nurse administrators and educators have the potential to influence the successful adoption of this innovation.


[Risk factors for falls and fractures at night in relation to lower urinary tract symptoms: a survey of outpatients and inpatients at a general hospital].
We investigated potential risk factors, including factors related to lower urinary tract symptoms (LUTS), for falls and fractures at night among outpatients and inpatients in a general hospital, via a questionnaire. The questionnaire included items to record the age, sex, number of consulting doctors, history of 11 particular medical diseases, LUTS, sleep, and falls and fractures at night. We distributed the questionnaire to 1,334 patients 51 years old or older in our hospital. Of the questionnaires completed, 96.9% were valid for analysis. Multivariate analyses revealed that "drinking water before bedtime or while in bed" was the strongest risk factor (odds ratio=7.499) for bone fractures while "postural syncope" was the strongest risk factor (odds ratio=5.041, except past medical history) for falls. In terms of LUTS, urge incontinence was a significant risk factor for falls.


[Role of the ORL anesthetist in foreseen or unforseen difficult intubations].
Difficult intubation (DI) is a daily problem in a ENT unit. The place of the ENT anesthesiologist in the management of a DI is both in his own unit and in the hospital as an expert in DI. An anesthesiologist working in a ENT unit should be an expert in techniques allowing to manage intubation and oxygenation in every situations: i.e. fiberscopic intubation, LMA and intubating LMA and transtracheal ventilation. The ENT anesthesiologist may also play a role in the management of a DI in the hospital as an expert, both helping to cope with a difficult airway and teaching airway skills and the value of having a plan before managing any airway.


Acute colchicine intoxication during clarithromycin administration.
To report a case of colchicine intoxication occurring with institution of clarithromycin. A 76-year-old man with familial Mediterranean fever (FMF) had received colchicine 1.5 mg daily for 6 years. The patient underwent 7 days of clarithromycin, amoxicillin, and omeprazole treatment for Helicobacter pylori-associated gastritis. Fever, abdominal pain, and diarrhea occurred 3 days after treatment initiation. On day 8, dehydration, pancytopenia, metabolic acidosis, and increased lipase level necessitated hospitalization. Alopecia was observed 2 weeks later. The patient recovered fully after the colchicine dosage was reduced to 0.5 mg/day and rehydration was performed. The previous dosage was then reinstituted without adverse reaction. An objective causality assessment revealed that the adverse event was probable. Continuous colchicine administration is used in treatment of microcrystalline arthritis, Behcet's disease, and FMF. Colchicine is primarily eliminated through biliary excretion. Renal elimination and cytochrome P450 metabolism play a less significant role. Colchicine is also a substrate of P-glycoprotein, a transporter involved in cellular efflux and elimination of numerous drugs. Three cases of intoxication have been reported when colchicine was combined with erythromycin, josamycin, or clarithromycin. Macrolides are inhibitors of P-glycoprotein and cytochrome P450-dependent enzymes and may decrease colchicine's biliary excretion through P-glycoprotein inhibition. Coadministration of colchicine and macrolides may impair colchicine elimination, resulting in excess drug exposure and toxicity. To this end, colchicine should be used with extreme caution in patients receiving P-glycoprotein inhibitors, particularly if they are elderly and/or renally compromised.


Two trocar laparoscopic varicocelectomy: approach and outcomes.
The surgical indications and proper management of varicoceles in the pediatric population continue to be controversial. Historically, open surgical approaches have had recurrence rates between 2% to 6% and a low rate of complications. We present a modified laparoscopic technique for the treatment of clinically significant varicoceles. Consecutive pediatric patients presenting with clinically significant varicoceles between May 2000 and July 2003 were considered for laparoscopic varicocelectomy. A 5-mm 2-port laparoscopic varicocelectomy was performed, with supraumbilical and contralateral lower quadrant placement of the trocars. The Harmonic scalpel was used to fulgurate the spermatic vessels in a nonartery sparing technique. Ten clinically significant varicoceles were identified in 9 patients, all of which were ligated with this technique. One patient was treated for bilateral varicoceles. Average operating room time was 53 minutes (range, 45 to 65). All patients were discharged from the ambulatory surgery unit and returned to their regular physical activity within 2 weeks after surgery. Upon clinical reevaluation 6 weeks post surgery, there was no evidence of varicocele recurrence or hydrocele formation, and all patients were asymptomatic. Our 2-port laparoscopic varicocelectomy is comparable to traditional open surgical approaches in recurrence and complication rates. This laparoscopic repair may be superior to open techniques in operating time, convalescence, and cosmesis. The procedure is easily mastered and does not require microsurgical skills.


Unusual Destruction of the Nasal Septum.
Extranodal Natural Killer/T-cell lymphoma (ENKTL) is the most common cause of nasal cell lymphoma. It manifests by progressive destruction of the facial midline features with nasal obstruction and local destruction of soft tissue. Therefore, establishing the diagnosis of this disease tends to be difficult. This is attributed to an extensive differential diagnosis of infectious, autoimmune, neoplastic and inflammatory etiologies. We herein report the case of a 63-year-old female who presented to our department for persistent nasal congestion resistant to symptomatic treatment that was found to have an ENKTL. In this paper, we discuss the pathogenesis, clinical and imaging findings, differential diagnosis, prognosis and treatment.


Age-related vascular pathology in transgenic mice expressing presenilin 1-associated familial Alzheimer's disease mutations.
Mutations in the presenilin 1 (PS1) gene are the most commonly recognized cause of familial Alzheimer's disease (FAD). Besides senile plaques, neurofibrillary tangles, and neuronal loss, Alzheimer's disease (AD) is also accompanied by vascular pathology. Here we describe an age-related vascular pathology in two lines of PS1 FAD-mutant transgenic mice that mimics many features of the vascular pathology seen in AD. The pathology was especially prominent in the microvasculature whose vessels became thinned and irregular with the appearance of many abnormally looped vessels as well as string vessels. Stereologic assessments revealed a reduction of the microvasculature in the hippocampus that was accompanied by hippocampal atrophy. The vascular changes were not congophilic. Yet, despite the lack of congophilia, penetrating vessels at the cortical surface were often abnormal morphologically and microhemorrhages sometimes occurred. Altered immunostaining of blood vessels with basement membrane-associated antigens was an early feature of the microangiopathy and was associated with thickening of the vascular basal laminae and endothelial cell alterations that were visible ultrastructurally. Interestingly, although the FAD-mutant transgene was expressed in neurons in both lines of mice, there was no detectable expression in vascular endothelial cells or glial cells. These studies thus have implications for the role of neuronal to vascular signaling in the pathogenesis of the vascular pathology associated with AD.


Comparison of Activator-Headgear and Twin Block Treatment Approaches in Class II Division 1 Malocclusion.
The purpose was to compare the treatment effects of functional appliances activator-headgear (AH) and Twin Block (TB) on skeletal, dental, and soft-tissue structures in class II division 1 malocclusion with normal growth changes in untreated subjects. The sample included 50 subjects (56% females) aged 8-13 years with class II division 1 malocclusion treated with either AH (n = 25) or TB (n = 25) appliances. Pre- and posttreatment lateral cephalograms were evaluated and compared to 50 untreated class II division 1 cases matched by age, gender, ANB angle, and skeletal maturity. A paired sample, independent samples tests and discriminant analysis were performed for intra- and intergroup analysis. Treatment with both appliances resulted in significant reduction of skeletal and soft-tissue facial convexity, the overjet, and the prominence of the upper lip in comparison to untreated individuals (p < 0.001). Retroclination of maxillary incisors and proclination of mandibular incisors were seen, the latter being significantly more evident in the TB group (p < 0.05). Increase of effective mandibular length was more pronounced in the TB group. In conclusion, both AH and TB appliances contributed successfully to the correction of class II division 1 malocclusion when compared to the untreated subjects with predominantly dentoalveolar changes.


Effect of asymptomatic postoperative epidural hematoma on recovery rate after surgery for myelopathy caused by thoracic ossified ligamentum flavum.
To analyze the clinical characteristics of thoracic ossified ligamentum flavum (OLF) and clarify prognostic factors. We retrospectively collected clinical data from the medical records of 29 patients who underwent decompressive surgery for myelopathy caused by thoracic OLF from 2011 to 2019. Associations between various clinical and radiological factors and surgical outcomes were analyzed. The mean preoperative and final follow-up modified Japanese Orthopaedic Association scores were 6.7 and 7.9 points, respectively (mean follow-up period, 22.4 months; P 0.0001). Univariate analysis revealed that preoperative symptom duration and postoperative epidural hematoma on magnetic resonance imaging (MRI) were significant surgical outcome predictors. The recovery rate was higher in patients without postoperative epidural hematoma (n = 16) than in those with postoperative epidural hematoma (n = 13; 38.7% ± 28.1% vs. 12.9% ± 24.4% mm; P = 0.01). Multiple regression analysis showed that postoperative epidural hematoma on MRI was a significant surgical outcome predictor (P 0.05). Posterior decompressive laminectomy and resection of OLF can be considered effective. Postoperative epidural hematoma on MRI may be an important surgical outcome predictor.


Induction of functional differentiation and growth inhibition in vitro of canine osteosarcoma by 22-oxacalcitriol, calcitriol and all-trans retinoic acid.
The effects of 22-oxacalcitriol (OCT), calcitriol and all-trans retinoic acid (ATRA) on the induction of functional differentiation and growth inhibition of the canine osteosarcoma cell line POS were investigated in vitro via bone differentiation markers and proliferation assays, respectively. The intracellular alkaline phosphatase (ALP) activity and the gamma-carboxyglutamic acid osteocalcin (GLA-OC) and procollagen type I C peptide (PIP) production were used as markers of differentiation. Treatment with 10(-8) M concentrations of all drugs for 72 h significantly inhibited growth (P < 0.0001) and increased ALP activity and GLA-OC and PIP production in POS. OCT, calcitriol and ATRA significantly increased the: ALP activity from 1.58 +/- 0.14 mumol/min/mg protein (mean +/- SD; control) to 2.50 +/- 0.09 (P < 0.0001), 2.30 +/- 0.14 (P < 0.0001) and 2.00 +/- 0.14 (P = 0.0008), respectively; GLA-OC production from 0.71 +/- 0.01 ng/ml (control) to 2.87 +/- 0.01 (P < 0.0001), 2.87 +/- 0.11 (P < 0.0001) and 1.36 +/- 0.06 (P < 0.0001), respectively; and PIP production from 433.91 +/- 23.29 ng/ml (control) to 536.54 +/- 15.46 (P = 0.0002), 497.06 +/- 1.99 (P = 0.0028) and 481.66 +/- 0.01 (P = 0.0104), respectively. This study demonstrated that treatment with these drugs induced a phenotypic maturation of POS cells into cells that exhibit the properties of functionally mature bone cells with parallel growth inhibition. The effects of these drugs on functional differentiation may be useful to complement the progression of a normal osteogenic differentiation process in the sarcoma.


An empirical comparison of information-theoretic criteria in estimating the number of independent components of fMRI data.
Independent Component Analysis (ICA) has been widely applied to the analysis of fMRI data. Accurate estimation of the number of independent components of fMRI data is critical to reduce over/under fitting. Although various methods based on Information Theoretic Criteria (ITC) have been used to estimate the intrinsic dimension of fMRI data, the relative performance of different ITC in the context of the ICA model hasn't been fully investigated, especially considering the properties of fMRI data. The present study explores and evaluates the performance of various ITC for the fMRI data with varied white noise levels, colored noise levels, temporal data sizes and spatial smoothness degrees. Both simulated data and real fMRI data with varied Gaussian white noise levels, first-order auto-regressive (AR(1)) noise levels, temporal data sizes and spatial smoothness degrees were carried out to deeply explore and evaluate the performance of different traditional ITC. Results indicate that the performance of ITCs depends on the noise level, temporal data size and spatial smoothness of fMRI data. 1) High white noise levels may lead to underestimation of all criteria and MDL/BIC has the severest underestimation at the higher Gaussian white noise level. 2) Colored noise may result in overestimation that can be intensified by the increase of AR(1) coefficient rather than the SD of AR(1) noise and MDL/BIC shows the least overestimation. 3) Larger temporal data size will be better for estimation for the model of white noise but tends to cause severer overestimation for the model of AR(1) noise. 4) Spatial smoothing will result in overestimation in both noise models. 1) None of ITC is perfect for all fMRI data due to its complicated noise structure. 2) If there is only white noise in data, AIC is preferred when the noise level is high and otherwise, Laplace approximation is a better choice. 3) When colored noise exists in data, MDL/BIC outperforms the other criteria.


New developments in occupational dermatology.
Occupational skin diseases according to BK No. 5101 - "severe or recurrent skin diseases which have forced the person to discontinue all occupational activities that caused or could cause the development, worsening, or recurrence of the disease" - is the most commonly reported notifiable occupational diseases in Germany. Following the optimization of measures of primary, secondary, and tertiary prevention, today most individuals affected are able to continue their profession. With the revision of the German ordinance on occupational diseases (BKV) in January 2015, skin cancer caused by UV irradiation was added to the list of occupational diseases. The new occupational disease (BK) 5103 is defined as "squamous cell carcinoma or multiple actinic keratoses of the skin caused by natural UV irradiation". In this context, "multiple" signifies the occurrence of either more than five individual actinic keratosis lesions over the course of 12 months or the presence of field cancerization of > 4 cm(2) . In the following review, important aspects of this new occupational disease will be highlighted and discussed.


Purinergic signalling in systemic sclerosis.
SSc is a chronic autoimmune rheumatic disease that involves numerous organs and presents major management challenges. The histopathologic hallmarks of SSc include vasculopathy, fibrosis and autoimmune phenomena involving both innate and adaptive immune systems. Purinergic signalling is a pathway that may be implicated in the pathophysiology of several of these disease manifestations. Extracellular purines are potent signalling mediators, which have been shown to be dysregulated in SSc. As examples, purines can exacerbate vasculopathy and provoke platelet dysfunction; as well as contributing to immune dysregulation. Elements of purinergic signalling further promote organ and tissue fibrosis in several disease models. Here, we provide an overview of extracellular purine metabolism in purinergic signalling and link disorders of these to the molecular pathology of SSc. We also discuss targeting the purinergic signalling and explore the translational applications for new therapeutic options in SSc.


A wearable sensor based multi-criteria-decision-system for real-time seizure detection.
This paper presents a wireless, low power and low cost two part wearable for real-time epileptic seizure detection. Using parameters of Electro-cardiograph (ECG), Electro-dermal Activity (EDA), body motion and breathing rate (BR), a novel multi-criteria-decision-system (MCDS) is proposed that reduces false alarms and true negatives. The combination of a chest and hand worn wearable continuously senses these parameters transmitting the data to a smart phone application via BLE 4.0 where long-short-term-memory (LSTM) based anomaly detection algorithms and logistic classifiers decide on the occurrence of the seizure in real time. A 96% precision and 90% recall is achieved through testing on synthetic data.


Tibial Bushing Wear at 28 Years of Follow-up After Rotating-Hinge Distal Femoral Replacement: A Case Report.
A 58-year-old woman presented with swelling, stiffness, and pain of the right knee 28 years after rotating-hinge distal femoral replacement after osteosarcoma resection. She underwent revision. There was wear through the entire thickness of the polyethylene tibial sleeve bushing, and the implant was well-fixed. The knee was reassembled with new bushings, sleeves, yoke, axle, poly, and a locking pin. This is the first described case of tibial sleeve bushing wear. It highlights the importance of early detection of potential complications and implant surveillance because it can enable surgeons to intervene with minor procedures, avoiding eventual catastrophic failure.


Changes in tension regulates proliferation and migration of fibroblasts by remodeling expression of ECM proteins.
Wound healing is a complicated but highly organized process in which cell migration and proliferation are actively involved. However, the process by which mechanical stretch regulates the proliferation and migration of human skin fibroblasts (HFs) and keratinocytes is poorly understood. Using a house built mechanical stretch device, we examined the HFs extracellular matrix (ECM) components changes under non-stretch, static stretch or cyclic stretch conditions. We further investigated the changes in ECM component protein expression levels in keratinocytes and analyzed the effects of individual ECM component on keratinocyte proliferation and migration. Particularly, the roles of calcium/calmodulin-dependent serine protein kinase (CASK) in the HF proliferation under cyclic stretch were investigated. Cyclic stretch suppressed HF proliferation compared with HFs without stretch or with static stretch. Cyclic stretch also led to a significant reduction in the levels of collagen I and a marked increase of fibronectin in HFs ECM. By contrast, collagen I levels increased and fibronectin levels decreased in response to non-stretch and static stretch conditions. After cyclic stretch, the proliferation of keratinocytes was inhibited by the cyclic stretch-induced ECM in HFs. The inoculation of keratinocytes with single ECM component suggested that collagen I was more capable of inducing cell proliferation than fibronectin, while it had less impact on cell migration compared with fibronectin. Furthermore, cyclic stretch induced by proliferation inhibition was associated with altered integrin β1-CASK signal pathway. The present results demonstrated the existence of HF-ECM-keratinocyte 'cross-talk' in cutaneous tissues. Thus, the integrin β1-CASK signal pathway in HFs may be involved in the outside-in signal transduction of extracellular stretch and the altered ECM component expression.


The role of Facebook groups in the management and raising of awareness of antidepressant withdrawal: is social media filling the void left by health services?
Antidepressant withdrawal is experienced by about half of people who try to reduce or come off their medication. It can be a debilitating, long lasting process. Many clinicians misdiagnose or minimise symptoms, inadvertently prolonging suffering. Most are unable to help patients safely taper off. There has been little research into the peer support communities that are playing an increasingly important role in helping people withdraw from psychiatric medications. To illustrate the growth and activities of Facebook withdrawal groups, we examined 13 such groups. All were raising awareness of, and supporting individuals tapering off, antidepressants and were followed for 13 months. A further three groups were added for the last 5 months of the study. In June 2020, the groups had a total membership of 67,125, of which, 60,261 were in private groups. The increase in membership for the 13 groups over the study period was 28.4%. One group was examined in greater detail. Group membership was 82.5% female, as were 80% of the Administrators and Moderators, all of whom are lay volunteers. Membership was international but dominated (51.2%) by the United States (US). The most common reason for seeking out this group was failed clinician-led tapers. The results are discussed in the context of research on the prevalence, duration and severity of antidepressant withdrawal. We question why so many patients seek help in peer-led Facebook groups, rather than relying on the clinicians that prescribed the medications. The withdrawal experiences of tens of thousands of people remain hidden in these groups where they receive support to taper when healthcare services should be responsible. Further research should focus on the methods of support and tapering protocols used in these groups to enable improved, more informed support by clinicians. Support from Governments and healthcare agencies is also needed, internationally, to address this issue.


Cardiovascular disease in obstructive sleep apnoea syndrome: the role of intermittent hypoxia and inflammation.
There is increasing evidence that intermittent hypoxia plays a role in the development of cardiovascular risk in obstructive sleep apnoea syndrome (OSAS) through the activation of inflammatory pathways. The development of translational models of intermittent hypoxia has allowed investigation of its role in the activation of inflammatory mechanisms and promotion of cardiovascular disease in OSAS. There are noticeable differences in the response to intermittent hypoxia between body tissues but the hypoxia-sensitive transcription factors hypoxia-inducible factor-1 and nuclear factor-kappaB appear to play a key role in mediating the inflammatory and cardiovascular consequences of OSAS. Expanding our understanding of these pathways, the cross-talk between them and the activation of inflammatory mechanisms by intermittent hypoxia in OSAS will provide new avenues of therapeutic opportunity for the disease.