Positive Salt Tolerance Modulation via Vermicompost Regulation of SOS1 Gene Expression and Antioxidant Homeostasis in Viciafaba Plant.
Strategic implementation of vermicompost as safe biofertilizer besides defensing saline soils offer dual function solving problems in developing countries. The current study aims to utilize vermicompost (VC) for amelioration of 200mM NaCl in Vicia faba Aspani cultivar and investigate the molecular role of salt overly sensitive pathway (SOS1). The experiment was conducted following a completely randomized design with three replicates. Treatments include 0; 2.5; 5; 10; 15% dried VC intermingled with soil mixture (clay: sand; 1:2) and/or 200 mM NaCl. The results show that salinity stress decreased broad bean fresh and dry weight; and K+/Na+. However, malonedialdehyde and H2O2 contents; increased. Application of 10% VC and salinity stress increases Ca2+ (41% and 50%), K+/Na+ (125% and 89%), Mg2+ (25% and 36%), N (8% and 11%), indole acetic acid (70% and 152%) and proteins (9% and 13%) for root and shoot, respectively, in comparison to salt treated pots. Moreover, all examined enzymatic antioxidants and their substrates increased, except glutathione reductase. A parallel decrease in abscisic acid (75% and 29%) and proline (59% and 58%) was also recorded for roots and leaves, respectively. Interestingly, the highly significant increase in gene expression of SOS1 (45-fold) could drive defense machinery of broad bean to counteract 200 mM NaCl.


DNA methylation and the hygiene hypothesis: connecting respiratory allergy and childhood acute lymphoblastic leukemia.
Aim: The hygiene hypothesis states that a lack of infection in early-life suppresses immune system development, and is linked to respiratory allergy (RA) and childhood acute lymphoblastic leukemia (ALL) risk. Little is known about underlying mechanisms, but DNA methylation is altered in RA and ALL, and in response to infection. We investigated if aberrant methylation may be in common between these diseases and associated with infection. Materials & methods: RA and ALL disease-associated methylation signatures were compared and related to exposure-to-infection signatures. Results: A significant number of genes overlapped between RA and ALL signatures (p = 0.0019). Significant overlaps were observed between exposure-to-infection signatures and disease-associated signatures. Conclusion: DNA methylation may be a mediating mechanism through which the hygiene hypothesis is associated with RA and ALL risk.


HIF-1α and HIF-2α degradation is differentially regulated in nucleus pulposus cells of the intervertebral disc.
Studies of many cell types show that levels of hypoxia inducible factor (HIF)-1α and HIF-2α are primarily controlled by oxygen-dependent proteasomal degradation, catalyzed by HIF prolyl-hydroxylases (PHDs). However, in the hypoxic niche of the intervertebral disc, the mechanism of HIF-α turnover in nucleus pulposus cells is not yet known. We show that in nucleus pulposus cells HIF-1α and HIF-2α, degradation was mediated through 26S proteasome irrespective of oxygen tension. It is noteworthy that HIF-2α degradation through 26S proteasome was more pronounced in hypoxia. Surprisingly, treatment with DMOG, a PHD inhibitor, shows the accumulation of only HIF-1α and induction in activity of its target genes, but not of HIF-2α. Loss and gain of function analyses using lentiviral knockdown of PHDs and overexpression of individual PHDs show that in nucleus pulposus cells only PHD2 played a limited role in HIF-1α degradation; again HIF-2α degradation was unaffected. We also show that the treatment with inhibitors of lysosomal proteolysis results in a strong accumulation of HIF-1α and to a much smaller extent of HIF-2α levels. It is thus evident that in addition to PHD2 catalyzed degradation, the HIF-1α turnover in nucleus pulposus cells is primarily regulated by oxygen-independent pathways. Importantly, our data clearly suggests that proteasomal degradation of HIF-2α is not mediated by a classical oxygen-dependent PHD pathway. These results for the first time provide a rationale for the normoxic stabilization as well as the maintenance of steady-state levels of HIF-1α and HIF-2α in nucleus pulposus cells.


Apparent diffusion coefficient measurements of the pancreas, pancreas carcinoma, and mass-forming focal pancreatitis.
Mass-forming focal pancreatitis (FP) may mimic pancreatic cancer (PC) on magnetic resonance (MR) imaging, and the preoperative differential diagnosis is often difficult. Recently, the usefulness of diffusion-weighted imaging (DWI) in the diagnosis of pancreatic cancer has been reported in several studies. To investigate if apparent diffusion coefficient (ADC) measurements based on diffusion-weighted echo-planar imaging (DW-EPI) may distinguish between normal pancreas parenchyma, mass-forming focal pancreatitis, and pancreas carcinoma. MRI was performed on 64 patients: 24 with pancreas carcinoma (PC), 20 with mass-forming focal pancreatitis (FP), three patients with other focal pancreatic disease as well as 17 controls without any known pancreatic disease. Diffusion-weighted sequence with ADC maps and T2-weighted sequence for anatomical information was performed. Apparent diffusion coefficient (ADC) maps were automatically created and analyzed using a dedicated user interface. In the group with pancreas disease the abnormal parenchyma was detected by using T1- and T2-weighted images and the region of interest (ROI) was transferred exactly to the ADC map and the coefficients were registered. In the control group the ROI was set to the head of the pancreas followed by a similar registration of the ADCs. ADC values for mass-forming FP and PC differed significantly from ADC values for normal pancreas parenchyma (P = 0.001/P = 0.002). Mean ADC values for mass-forming FP were 0.69 ± 0.18 × 10(-3) mm(2)/s. ADC values for PC were 0.78 ± 0.11 × 10(-3) mm(2)/s, compared to ADC values of 0.17 ± 0.06 × 10(-3) mm(2)/s in the control group. However there was no significant difference in ADCs between PC and mass-forming FP (P = 0.15). ADC measurements clearly differentiated between normal pancreatic tissue and abnormal pancreas parenchyma (PC and mass-forming FP). However there is an overlap in values of PC and mass-forming FP, with the consequent problem of their correct identification.


Deletion mapping of chromosome region 9p21-p22 surrounding the CDKN2 locus in melanoma.
The cyclin-dependent kinase-4 inhibitor gene CDKN2, localized at chromosome region 9p21, has been shown to be a familial melanoma gene, though we found that mutations of it are rare in uncultured sporadic melanomas. To determine Whether the region of allelic loss at 9p21 frequently observed in sporadic melanomas includes the CDKN2 locus, new polymorphic microsatellite probes were isolated from the genomic segments surrounding the CDKN2 gene and used for the study of loss of heterozygosity (LOH) in melanoma. The LOH study of matched uncultured tumor-constitutional DNA pairs from 66 metastatic cutaneous and 19 primary uveal melanomas showed that 63% and 32% of the respective tumors suffered allelic loss in the 9p21 region. Two regions of common losses which did not include the CDKN2 locus were observed: in a region of common loss near the D9S157 locus, telomeric to the CDKN2 locus, deletions were observed in 51% of informative cases; in the other region of common loss, near the D9S171 locus, centromeric to the CDKN2 locus, deletions were observed in 47% of informative cases. At the D9S974 locus, located within 20 kb of the CDKN2 gene, deletions were observed in 43% of informative cases. Homozygous deletions of the CDKN2 locus were observed in 8 cases of cutaneous melanoma and 2 cases of uveal melanoma; mutations in CDKN2 exon 2 were found in 2 of the 46 cases with allelic deletion in 9p21. Our results support the following conclusions: (i) somatic mutation of the CDKN2 gene is rare in sporadic melanomas with allelic loss at 9p21; (ii) homozygous loss is more frequent than mutation of the CDKN2 gene in sporadic melanomas; (iii) at 9p21-p23 genes other than CDKN2 may be involved in the development of sporadic melanomas.


Cell Cycle-specific Measurement of γH2AX and Apoptosis After Genotoxic Stress by Flow Cytometry.
The presented method or slightly modified versions have been devised to study specific treatment responses and side effects of various anti-cancer treatments as used in clinical oncology. It enables a quantitative and longitudinal analysis of the DNA damage response after genotoxic stress, as induced by radiotherapy and a multitude of anti-cancer drugs. The method covers all stages of the DNA damage response, providing endpoints for induction and repair of DNA double-strand breaks (DSBs), cell cycle arrest and cell death by apoptosis in case of repair failure. Combining these measurements provides information about cell cycle-dependent treatment effects and thus allows an in-depth study of the interplay between cellular proliferation and coping mechanisms against DNA damage. As the effect of many cancer therapeutics including chemotherapeutic agents and ionizing radiation is limited to or strongly varies according to specific cell cycle phases, correlative analyses rely on a robust and feasible method to assess the treatment effects on the DNA in a cell cycle-specific manner. This is not possible with single-endpoint assays and an important advantage of the presented method. The method is not restricted to any particular cell line and has been thoroughly tested in a multitude of tumor and normal tissue cell lines. It can be widely applied as a comprehensive genotoxicity assay in many fields of oncology besides radio-oncology, including environmental risk factor assessment, drug screening and evaluation of genetic instability in tumor cells.


Network analysis of psychotic manifestations among cocaine users.
Psychotic experiences can be described along a continuum ranging from no psychotic experience at all, to clinical psychotic disorder. Any individual in the general population may encounter psychotic experiences under certain circumstances. Transient Cocaine Induced Psychotic Symptoms (TCIPS) are a well described model of such circumstances. Therefore, our aim was to use a network analysis to get a better knowledge on the architecture of previously described risk factors and how they contributed to two different measures of psychosis (psychosis proneness and transient cocaine induced psychotic symptoms) This study is a secondary analysis conducted among 180 cocaine users in addiction care centers in Paris and Paris suburb, who were evaluated with the PDI (Peters Delusion Inventory) and the SAPS-CIP (Scale for the Assessment of Psychotic Symptoms - Cocaine Induced Psychosis). Schizophrenia diagnosis was extracted from medical record. Relevant variables significantly associated with SAPS-CIP total score or PDI at the first step were included in a network analysis to better figurate their respective associations. The network centrality measures showed that the product preferentially used (crack vs cocaine) was related to TCIPS, psychosis proneness and, to a lesser extent, schizophrenia. Secondly, in this model TCIPS is a mediator between intensive cocaine use and psychosis proneness. Thirdly, this study refines the previous knowledge on heavy cannabis use being a risk factor for TCIPS. The observed link is not direct but mediated by psychosis proneness.


Default Mode Network Alterations Induced by Childhood Trauma Correlate With Emotional Function and SLC6A4 Expression.
As one of the most studied resting-state functional networks, default mode network (DMN) is related to pathogenesis in neuropsychiatry. However, it is unclear whether changed DMN connectivity is transformed into vulnerability to psychopathology in adults who experienced childhood trauma, and what is the underlying genetic basis. Exploring the effect of DMN on environment-behavior pathway and the related genetic modulation mechanisms could further a better understanding of psychiatric pathogenesis and early prevention strategy. Two hundred and sixteen young adults with varying levels of early trauma indexed by the Childhood Trauma Questionnaire (CTQ) were recruited from the community. Static and dynamic functional connectivity based on DMN seeds and independent component analysis based on whole-brain voxels were combined to explore DMN alterations related to the CTQ score. Relationships between CTQ score, DMN connectivity, and behavioral scores were confirmed by mediation effect analysis. Imaging-genomic correlations were further used to identify risk genes whose expression was associated with the DMN changes. Dysregulated DMN connectivity was found both in seed-level and voxel-level analyses. Moreover, the functional disruption in the left temporal pole, right parahippocampal gyrus, and frontoparietal connectivity mediated the effects of childhood trauma on emotional behavior. The serotonin transporter gene was identified and might suggest the biological underpinning of the relationship between childhood trauma, DMN, and emotion regulation. Changed DMN may be useful as biomarkers to provide a powerful supplement to psychological evaluation related to childhood trauma. Combined with gene expression profiles, our findings advance a more integrative understanding of DMN alterations induced by childhood trauma, and clarify its implications for psychiatric pathogenesis and early prevention strategies.


Successful ECT in a patient with hydrocephalus, shunt, hypopituitarism, and paraplegia.
A 25-year-old patient with paraplegia, hypopituitarism, hydrocephalus, and a ventriculoperitoneal shunt was successfully treated with a course of bilateral electroconvulsive therapy (ECT) for major depression. Brain imaging studies and neurology/ endocrinology consultations were obtained prior to the use of ECT. Throughout the course of ECT, his replacement hormonal therapy continued. Prior to each ECT, additional parenteral hydrocortisone was also administered. Consistent with the previously published reports, the patient did not experience any neurological deterioration. A brief review of the literature on the use of ECT in patients with panhypopituitarism, spinal cord injury, and hydrocephalus is presented.


Water flow inside various geometric nano-confinement channels.
In nano-confined systems, the properties of a fluid are different from those of macroscopic systems, and the properties of a nanotube can significantly affect water transport. However, our knowledge of the effects of nanotube shape is far from adequate. In the present work, we study the properties of a fluid transporting in different nano-confined configurations by molecular dynamics simulations. This study is aimed at gaining insight into the transport of water molecules in carbon nanotubes with different configurations. We find that the closer of channel shape to the circular nanotube (more sides of the channel), the lower friction coefficient of the solid-liquid interface has and the friction coefficient of nanochannels increases with R when R < 1.0 nm. The friction coefficient converges to a stable value (close to the friction coefficient of graphene/water) when R > 1.0 nm. A variety of configurations leads to the variation of the fluid properties in nanotubes. Our results can be applied to the nanofluid properties of a complex channel structure and water nanochannel microscopic design.


White-matter abnormalities in brain during early abstinence from methamphetamine abuse.
Previous studies revealed microstructural abnormalities in prefrontal white matter and corpus callosum of long-term abstinent chronic methamphetamine abusers. In view of the importance of the early abstinence period in treatment retention, we compared 23 methamphetamine-dependent subjects abstinent from methamphetamine for 7-13 days with 18 healthy comparison subjects. As certain metabolic changes in the brain first manifest after early abstinence from methamphetamine, it is also possible that microstructural white-matter abnormalities are not yet present during early abstinence. Using diffusion tensor imaging at 1.5 T, fractional anisotropy (FA) was measured in prefrontal white matter at four inferior-superior levels parallel to the anterior commissure-posterior commissure (AC-PC) plane. We also sampled FA in the corpus callosum at the midline and at eight bilateral, fiber-tract sites in other regions implicated in effects of methamphetamine. The methamphetamine group exhibited lower FA in right prefrontal white matter above the AC-PC plane (11.9% lower; p = 0.007), in midline genu corpus callosum (3.9%; p = 0.019), in left and right midcaudal superior corona radiata (11.0% in both hemispheres, p's = 0.020 and 0.016, respectively), and in right perforant fibers (7.3%; p = 0.025). FA in left midcaudal superior corona radiata was correlated with depressive and generalized psychiatric symptoms within the methamphetamine group. The findings support the idea that methamphetamine abuse produces microstructural abnormalities in white matter underlying and interconnecting prefrontal cortices and hippocampal formation. These effects are already present during the first weeks of abstinence from methamphetamine and are linked to psychiatric symptoms assessed during this period.


A Randomized, Triple-Blind, Placebo-Controlled, Add-On Clinical Trial to Evaluate the Efficacy of Emblica officinalis in Uncontrolled Hypertension.
Introduction. Emblica officinalis (EO) has some cardiovascular effects, and there are some animal studies that show its antihypertensive effect. This study was conducted to determine the effect of combination of EO with standard therapy on the systolic blood pressure (SBP) and diastolic blood pressure (DBP) in patients with uncontrolled hypertension. Materials and Methods. This was a randomized, triple-blind, placebo-controlled, 8-week study. Ninety-two patients with uncontrolled hypertension despite taking hypotensive drugs were randomly assigned into two groups to take EO (500 mg/TDS after meal) or placebo in combination with standard antihypertensive drugs. After 2, 4, 6, and 8 weeks of intervention, SBP and DBP and heart rate (HR) were measured. Data were analyzed by SPSS software using repeated measures ANOVA. Results. Eighty-one patients (41 in the drug group and 40 in the placebo group) completed the study for 8 weeks and were analyzed. The mean ± standard deviation of age was 53.64 ± 10.01 years. SBP decreased as 15.6 ± 8.23% in the EO group and 6.3 ± 7.49% in the placebo group (P < 0.001). DBP decreased as 12.3 ± 7.87% and 3.88 ± 7.98%, respectively (P < 0.001). Time effect was not significant, but the group effect was significant (F = 13.875, P=0.001 for systolic BP and F = 18.948, P < 0.001 for diastolic BP). No side effects were reported during the study. Conclusion. Eight-week combination therapy of EO with standard antihypertensive drugs significantly reduced the SBP and DBP more than placebo in patients with uncontrolled hypertension.


Prevention of platelet aggregation and arterial thrombosis using a modified Shenzhu Guanxin Formula.
Modified Shenzhu Guanxin Formula (mSGF) has beneficial effects in coronary artery disease. Previously, we found that mSGF inhibited platelet aggregation in rats. In the present study we further investigated the antiplatelet and antithrombotic activities of mSGF in rats. Rats were orally administered mSGF (4.2, 8.4, or 16.8 g crude drug/kg), the adenosine 5'-diphosphate (ADP) receptor antagonist clopidogrel (7.875 mg/kg), or saline once a day for 7 days. The effects of mSGF on platelet aggregation were measured. Levels of cyclic adenosine monophosphate (cAMP) and phosphoinositide 3-kinase (PI3K) signaling were analyzed by ELISA and western blotting, respectively. The antithrombotic effect of mSGF was investigated using a FeCl3-induced carotid arterial thrombosis model and effects on bleeding time were assessed in a rat tail transection model. mSGF significantly inhibited ADP-induced platelet aggregation in a dose-dependent manner, elevated cAMP levels and inhibited phosphorylation of extracellular signal-regulated kinase (ERK) and PI3K/protein kinase B (Akt). Moreover, mSGF dose-dependently inhibited thrombosis in a FeCl3-induced carotid arterial thrombus model and had a significantly smaller effect on bleeding time compared with clopidogrel. mSGF represents a potent and safe antithrombotic agent whose antiplatelet activity is probably mediated through blockade of PI3K/Akt signaling and increased cAMP generation.


Evaluation the efficacy of prophylactic tamsulosin in preventing acute urinary retention and other obstructive urinary symptoms following colporrhaphy surgery.
Postoperative urinary retention (POUR) is defined as a disability in urinary excision after surgery. There are several strategies to prevent POUR, such as tamsulosin, which is a selective antagonist at alpha-1A and alpha-1B-adrenoceptors which reduces the bladder outlet resistance. The aim of this study was to investigate the efficacy of prophylactic tamsulosin in preventing acute urinary retention and other obstructive urinary symptoms following colporrhaphy surgery. This study was a randomized, double-blind clinical trial. A total of 130 patients who were candidates for colporrhaphy were divided into two groups: the intervention group (65 subjects received 0.4 mg tamsulosin in a single dose at the time of sleeping) and the control group (65 subjects received placebo at the same time as the intervention group). The incidence of acute urinary retention and other obstructive urethral symptoms and the mean urination volume after catheterization were recorded 24 h after operation. Patients' demographic and clinical data were analyzed using SPSS version 20 software using Chi-square and Fisher's tests. There was a significant difference in the incidence of acute urinary retention, decrease in urine flow diameter, and the mean residual urine volume Post Void Residual (PVR) in the bladder, and the incidence of these symptoms decreased in the tamsulosin recipient group. The incidence of other symptoms of acute urinary retention was not significantly different when compared between both the groups. It seems that the use of prophylactic tamsulosin is more effective in decreasing the incidence of acute urinary retention, decreasing the PVR in the bladder, and decreasing the diameter of the urine flow in patients after colporrhaphy.


Memory impairment and deep brain structures.
Clinical and neuropsychological investigations were performed using the Luriya method in 141 patients with arteriovenous malformations (AVM). These included 27 patients with AVM in different parts of the caudate nucleus, 34 with AVM in the thalamus, 39 with AVM in the hippocampal formation, and 41 with AVM in the cingulate gyrus. A total of 102 patients underwent surgery. Patients with AVM in various locations showed common memory impairments as well as individual features of memory disturbances depending on which structures were affected. The common feature was the development of an amnesiac symptom complex resembling Korsakov's syndrome. These lesions developed only in patients with combined damage to deep structures (preoperatively in patients with ventricular hemorrhages); with the exception of patients with AVM of the caudate nucleus, memory impairments were modality-non-specific; all patients showed impairment of auditory-speech memory at the late phase and of visual memory in terms of indirect recall. Memory impairments characteristic of lesions to individual structures were the presence of functional asymmetry of memory defects in available of the caudate nucleus and thalamus (if only speech problems were present) and constant inclusions and contaminations in patients with AVM of the cingulate gyrus. It is suggested that certain aspects of memory function may have been duplicated in different structures during evolution and that each structure makes its own contribution to overall memory function.


Creutzfeldt-Jakob disease in a physician: a review of the disorder in health care workers.
We describe a 58-year-old physician who developed Creutzfeldt-Jakob disease (CJD) 30 years after formal training in pathology. To the best of our knowledge, he is the sixth physician and the 24th health care worker reported with CJD. We summarize the available data on these health care workers.


Successful medical management of intra-abdominal abscesses in 4 adult horses.
Four adult horses with large intra-abdominal abscesses, suspected to be complications of strangles, were treated with systemic antibiotics alone and made a full recovery. The 100% survival rate is significantly better than other reported survival rates. The median duration of treatment (35 days) was shorter than in most previous reports. This study suggests that penicillin G can be used for successful treatment of strangles associated intra-abdominal abscesses in horses.


Interaction between the 2'-5' oligoadenylate synthetase-like protein p59 OASL and the transcriptional repressor methyl CpG-binding protein 1.
The human 2'-5' oligoadenylate synthetases (OAS) form a conserved family of interferon-induced proteins consisting of four genes: OAS1, OAS2, OAS3 and the 2'-5' oligoadenylate synthetase-like gene (OASL). When activated by double-stranded RNA, OAS1-3 polymerize ATP into 2'-5'-linked oligoadenylates; 2'-5'-linked oligoadenylates, in turn, activate a latent endoribonuclease that degrades viral and cellular RNAs. In contrast, while the p59 OASL protein is highly homologous to the OAS family (45% identity), its 350 amino acid N-terminal domain lacks 2'-5' oligoadenylate synthetase activity. A C-terminal 164 amino acid domain, which is 30% homologous to a tandem repeat of ubiquitin, further distinguishes the p59 OASL protein and suggests that it serves a biological role which is distinct from other OAS family members. To dissect the function of p59 OASL, we utilized the yeast two-hybrid system to identify interacting proteins. Methyl CpG-binding protein 1 (MBD1), which functions as a transcriptional repressor, was identified as a strong p59 OASL interactor. Interestingly, like p59 OASL, transcription of the MBD1 gene was induced by interferon, indicating that these genes are co-ordinately regulated. The interaction was confirmed in vitro and in vivo and was mapped to the ubiquitin-like domain of p59 OASL. The p59 OASL-MBD1 interaction was specific, because p59 OASL did not interact with any of the other MBD family members and MBD1 did not interact with OAS1. These findings link the p59 OASL with MBD1 transcriptional control in the context of an interferon-stimulated cell, and provide the basis for future studies to examine the functional role of this interaction.


Yiguanjian decoction enhances fetal liver stem/progenitor cell-mediated repair of liver cirrhosis through regulation of macrophage activation state.
To investigate whether Yiguanjian decoction (YGJ) has an anti-liver cirrhotic effect and whether it regulates hepatic stem cell differentiation. A rat model of liver cirrhosis was established via subcutaneous injection of carbon tetrachloride (CCl4) for 8 wk. From the beginning of the ninth week, the rats received 2-acetylaminofluorene (2-AAF) by oral gavage and a DLK-1+ fetal liver stem/progenitor cell (FLSPC) transplant or an FLSPC transplant in combination with YGJ treatment for 4 wk. In vitro, lipopolysaccharide (LPS)-activated macrophages were co-cultured with WB-F344 cells, and the differentiation of WB-F344 cells was observed in the presence and absence of YGJ treatment. FLSPC transplantation improved liver function and histopathology, and inhibited the activation of the non-canonical Wnt signaling pathway, while activating the canonical Wnt signaling pathway. YGJ enhanced the therapeutic effects of FLSPCs and also promoted the liver regeneration differentiation of FLSPCs into hepatocytes. In vitro, LPS-activated macrophages promoted the differentiation of WB-F344 cells into myofibroblasts, and the canonical Wnt signaling was inhibited while the non-canonical Wnt signaling was activated in WB-F344 cells. YGJ suppressed the activation of macrophages and then inhibited non-canonical Wnt signaling and promoted canonical Wnt signaling. YGJ enhances FLSPC-mediated repair of liver cirrhosis through regulation of macrophage activation state, and YGJ in combination with stem cell transplantation may be a suitable treatment for end-stage liver cirrhosis.


Ewing sarcoma of the cubitus reconstructed by a non vascularized autologous fibular graft.
A 19-year-old white man presented with an Ewing sarcoma of the left cubitus. A preoperative chemotherapy was administered according to the T9 Rosen protocol. A wide excision was performed with a 19 cm bone defect, reconstructed in the same operating time by a non vascularized autologous fibular transfer. The postoperative chemotherapy was administered without any major problem. Both surgical and functional evolution are here presented and the osteointegration is evaluated. A discussion of this type of reconstruction is presented evaluating donor site morbidity and possible complications.


A rapid and efficient mass spectrometric method for the analysis of explosives.
The high explosives trinitrotoluene, nitroglycerine, pentaerythritol tetranitrate and hexahydro-1,3,5-trinitro-1,3,5-triazine are efficiently ionised under negative ion atmospheric pressure chemical ionisation (APCI) conditions. The limit of detection is improved, in some cases by several orders of magnitude, by complexation with chlorine demonstrating this to be a highly suitable method for enhancing the detection capabilities for explosives. The spectra produced from introduction of the analytes in a liquid matrix, with and without chlorine present, contain a number of ions that arise through secondary processes including breakdown and adduct formation. Sample introduction into an APCI source in air, via a heated-plate inlet with a supplementary feed of dichloromethane, produces improved response for the chloride adducts of the analytes and minimises their decomposition during analysis. The tandem mass spectra produced from the chloride adducts are simple. Optimisation of the trapping parameters of the ion trap detector enhances selected transitions, yields highly reproducible spectra and improves the limits of detection for MS/MS analysis.


Randomized, controlled study of telcagepant in patients with migraine and coronary artery disease.
To evaluate the efficacy of telcagepant in patients with migraine and coronary artery disease. Calcitonin gene-related peptide receptor antagonists, such as telcagepant, may be useful for acute migraine treatment in patients with cardiovascular disease, a population for whom triptans are contraindicated. Randomized, double-blind, two-period (6 weeks per period) crossover study in patients with stable coronary artery disease and migraine. Patients were randomized 1:1 to either: (1) Period 1: telcagepant (280-mg tablet/300-mg capsule), Period 2: acetaminophen (1000-mg); or (2) Period 1: placebo for attack 1 then acetaminophen for subsequent attacks, Period 2: telcagepant. Patients could treat up to 12 migraine attacks per period to assess the tolerability of telcagepant. The primary efficacy analysis evaluated telcagepant vs placebo on 2-hour pain freedom during the first attack of Period 1. One hundred and sixty-five of the planned 400 patients were enrolled, and 114 took at least one dose of treatment. Telcagepant was not statistically different from placebo for 2-hour pain freedom (25.0% vs 18.9%, odds ratio = 1.62 [95% confidence interval: 0.62, 4.25]). The median number of attacks treated per period was 3. No cardiovascular thrombotic adverse events occurred within 14 days of dosing. The study was underpowered due to enrollment difficulties and did not demonstrate a significant efficacy difference between telcagepant and placebo for the treatment of a migraine attack in patients with stable coronary artery disease. Telcagepant was generally well tolerated for acute intermittent migraine treatment in these patients.


Klinefelter Syndrome Presenting as Suicidal Attempt.
Klinefelter syndrome is the most common sex chromosome disorder, manifested as hypogonadism, gynecomastia, and impaired spermatogenesis. It is characterized by the presence of one or more extra X chromosomes. Patients with Klinefelter syndrome are highly susceptible to psychiatric disturbances as compared to the general population. These include personality changes, depression, and psychosis. Rarely, these psychiatric disturbances can be the presenting manifestations in these individuals. Hence, meticulous clinical examination should be performed in every patient of psychiatric illness to rule out systemic illness like hypogonadism, as the treatment of underlying medical condition can be beneficial in alleviation of the psychiatric illness.


Fabrication of Photothermo-Responsive Drug-Loaded Nanogel for Synergetic Cancer Therapy.
Temperature stimulus, easy modulation in comparison to other environmental stimuli, makes thermo-responsive nanocarriers popular in the applications of controlled drug release for cancer therapy. In this study, photosensitive sodium copper chlorophyllin (SCC) was incorporated into thermo-responsive polymeric nanogels consisted of N-isopropylacrylamide and N-(hydroxymethyl)acrylamide. Significant heat was generated from the SCC-containing nanogels under the exposure to 532-nm green laser, and resulted in cell mortality. The thermo-responsive nanogel loaded with 5-FU, an anti-cancer drug, released the drug explosively when exposed to green laser. The combination of hyperthermia and temperature-induced drug release via green laser irradiation greatly enhanced cell mortality to a maximal extent. Such photothermo-responsive nanogel possesses a great potential in anti-cancer treatment.


Agathis robusta Bark Essential Oil Effectiveness against COVID-19: Chemical Composition, In Silico and In Vitro Approaches.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2), the causative agent of Coronavirus Disease 2019 (COVID-19), has seriously threatened global health. Alongside the approved vaccines, the discovery of prospective anti-COVID-19 drugs has been progressively targeted. Essential oils (EOs) provide a rich source of compounds with valuable antiviral activities that may contribute as effective agents against COVID-19. In this study, the EO of Agathus robusta bark was investigated for its chemical composition and its antiviral activity against SARS-CoV2. Overall, 26 constituents were identified by gas chromatography-mass spectrometry (GC-MS) analysis. α-Pinene, tricyclene, α-terpineol, limonene, d-camphene, trans-pinocarveol, α-phellandren-8-ol, L-β-pinene and borneol were the major components. In silico docking of these constituents against viral key enzymes, spike receptor-binding domain (RBD), main protease (Mpro) and RNA-dependent RNA polymerase (RdRp), using Molecular Operating Environment (MOE) software revealed good binding affinities of the components to the active site of the selected targets, especially, the RBD. In Vitro antiviral MTT and cytopathic effect inhibition assays demonstrated a promising anti SARS-CoV2 for A. robusta bark EO, with a significant selectivity index of 17.5. The results suggested using this EO or its individual components for the protection against or treatment of COVID-19.


Additional weighting for education affects estimates from a National Health Interview Survey.
National Health Interview Surveys are used to produce country-wide results for a substantial number of health indicators. However, if some educational groups are underrepresented in the sample, estimates may be biased. This study investigated the impact of the use of post-stratification weights that adjust for the population distribution by education on estimates from the Belgian Health Interview Survey 2013. For 25 health-related indicators that match the European Core Health Indicator shortlist, estimates were computed using two different sets of post-stratification weights: one based on age group, gender and province only and the other one including also education. The Census 2011 was used as auxiliary data source. Statistical differences between the two estimates were assessed with the Delta method. If education is not included as post-stratification weighting factor, low educational groups (ISCED 0-2) represent 31.1% of the total study population aged 25 years and older. If education is taken into account this proportion rises to 40.3%. The use of post-stratification weights adjusting for the population distribution by education has an impact on several survey estimates. The most pronounced effect is an increase in the estimated proportion of people with diabetes (+0.73%; 95% CI 0.19-1.27; relative increase +11.6%), asthma (+0.52%; 95% CI, 0.06-0.98; relative increase +12.4%) and difficulties to cover their health expenses (+2.31%; 95% CI, 1.52-3.10; relative increase +9.4%). Including education in the calculation of post-stratification weights reduces bias due to educational differences in survey participation. Auxiliary information used to calculate post-stratification weights for national health surveys should include education.


Oxidative stress induces hypomethylation of LINE-1 and hypermethylation of the RUNX3 promoter in a bladder cancer cell line.
Increased oxidative stress and changes in DNA methylation are frequently detected in bladder cancer patients. We previously demonstrated a relationship between increased oxidative stress and hypomethylation of the transposable long-interspersed nuclear element-1 (LINE-1). Promoter hypermethylation of a tumor suppressor gene, runt-related transcription factor 3 (RUNX3), may also be associated with bladder cancer genesis. In this study, we investigated changes of DNA methylation in LINE-1 and RUNX3 promoter in a bladder cancer cell (UM-UC-3) under oxidative stress conditions, stimulated by challenge with H2O2 for 72 h. Cells were pretreated with an antioxidant, tocopheryl acetate for 1 h to attenuate oxidative stress. Methylation levels of LINE-1 and RUNX3 promoter were measured by combined bisulfite restriction analysis PCR and methylation-specific PCR, respectively. Levels of LINE-1 methylation were significantly decreased in H2O2-treated cells, and reestablished after pretreated with tocopheryl acetate. Methylation of RUNX3 promoter was significantly increased in cells exposed to H2O2. In tocopheryl acetate pretreated cells, it was markedly decreased. In conclusion, hypomethylation of LINE-1 and hypermethylation of RUNX3 promoter in bladder cancer cell line was experimentally induced by reactive oxygen species (ROS). The present findings support the hypothesis that oxidative stress promotes urothelial cell carcinogenesis through modulation of DNA methylation. Our data also imply that mechanistic pathways of ROS-induced alteration of DNA methylation in a repetitive DNA element and a gene promoter might differ.


Redox balance in the pathogenesis of nonalcoholic fatty liver disease: mechanisms and therapeutic opportunities.
Nonalcoholic fatty liver disease (NAFLD) is currently the most common liver disease in the world. It encompasses a histological spectrum, ranging from simple, nonprogressive steatosis to nonalcoholic steatohepatitis (NASH), which may progress to cirrhosis and hepatocellular carcinoma. While liver-related complications are confined to NASH, emerging evidence suggests both simple steatosis and NASH predispose to type 2 diabetes and cardiovascular disease. The pathogenesis of NAFLD is currently unknown, but accumulating data suggest that oxidative stress and altered redox balance play a crucial role in the pathogenesis of steatosis, steatohepatitis, and fibrosis. We will examine intracellular mechanisms, including mitochondrial dysfunction and impaired oxidative free fatty acid metabolism, leading to reactive oxygen species generation; additionally, the potential pathogenetic role of extracellular sources of reactive oxygen species in NAFLD, including increased myeloperoxidase activity and oxidized low density lipoprotein accumulation, will be reviewed. We will discuss how these mechanisms converge to determine the whole pathophysiological spectrum of NAFLD, including hepatocyte triglyceride accumulation, hepatocyte apoptosis, hepatic inflammation, hepatic stellate cell activation, and fibrogenesis. Finally, available animal and human data on treatment opportunities with older and newer antioxidant will be presented.


Efficient Simulation of Finite-Temperature Open Quantum Systems.
Chain-mapping techniques in combination with the time-dependent density matrix renormalization group are a powerful tool for the simulation of open-system quantum dynamics. For finite-temperature environments, however, this approach suffers from an unfavorable algorithmic scaling with increasing temperature. We prove that the system dynamics under thermal environments can be nonperturbatively described by temperature-dependent system-environmental couplings with the initial environment state being in its pure vacuum state, instead of a mixed thermal state. As a consequence, as long as the initial system state is pure, the global system-environment state remains pure at all times. The resulting speed-up and relaxed memory requirements of this approach enable the efficient simulation of open quantum systems interacting with highly structured environments in any temperature range, with applications extending from quantum thermodynamics to quantum effects in mesoscopic systems.


Organophosphorus chemicals: potent inhibitors of the human metabolism of steroid hormones and xenobiotics.
Although it has been known for some time that organophosphate chemicals containing the P = S moiety are irreversible inhibitors of cytochrome P450, this knowledge has not been generally applied to the human metabolism of xenobiotics. Recent studies have demonstrated that organophosphate insecticides containing this moiety are potent inhibitors of the metabolism of both xenobiotics and endogenous substrates by human liver microsomes and by specific human cytochrome P450 isoforms.


Radiotherapy and L-triiodothyronine in the treatment of high-grade astrocytoma.
From January 1983 to March 1984, eight patients with high-grade astrocytoma received postoperative irradiation concomitantly with triiodothyronine at the Radiation Therapy Department of the I. González Martínez Oncologic Hospital in San Juan, Puerto Rico. There were no complications related to treatment. One patient is alive without evidence of disease at 39 months and seven patients died with disease, one of whom lived for 3 yr. The survival curve for these patients is similar to the survival curve of 18 patients treated at the University of Chicago by surgery, radiation, and triiodothyronine. The value of triiodothyronine as an adjuvant in the treatment of high grade astrocytoma should be further investigated.


Role of exercises and drills in the evaluation of public health in emergency response.
Public health agencies have been participating in emergency preparedness exercises for many years. A poorly designed or executed exercise, or an unevaluated or inadequately evaluated plan, may do more harm than good if it leads to a false sense of security, and results in poor performance during an actual emergency. At the time this project began, there were no specific standards for the public health aspects of exercises and drills, and no defined criteria for the evaluation of agency performance in public health. The objective of this study was to develop defined criteria for the evaluation of agency performance. A Delphi panel of 26 experts in the field participated in developing criteria to assist in the evaluation of emergency exercise performance, and facilitate measuring improvement over time. Candidate criteria were based on the usual parts of an emergency plan and three other frameworks used elsewhere in public health or emergency response. The response rate from the expert panel for Delphi Round I was 74%, and for Delphi Round II was 55%. This final menu included 46 public health-agency level criteria grouped into nine categories for use in evaluating an emergency drill or exercise at the local public health level. Use of the public health-specific criteria developed through this process will allow for specific assessment and planning for measurable improvement in a health agency over time.


Analysis and cytologic characterization of hemocytes from freshwater mussels (Quadrula sp.).
Freshwater mussels are among the most endangered taxa in North America and minimally invasive techniques to evaluate their health are needed. The objective of this study was to develop a standardized approach for identifying and enumerating the cellular components of freshwater mussel hemolymph. Hemocyte clumping, total hemocyte count, and hemocyte morphology were compared in untreated hemolymph or hemolymph treated with formalin, sodium citrate, sodium heparin, EDTA, water, or l-cysteine. Morphology was then used to categorize hemocytes and perform a 100-cell differential. Treatment with formalin or >25 mg/mL l-cysteine reduced hemocyte clumping, although only formalin significantly increased the total hemocyte count. However, formalin also induced crenation that impaired hemocyte identification. Both EDTA and sodium citrate-induced hemocyte degranulation while sodium citrate and >40 mg/mL l-cysteine-induced cell lysis. Hemocytes could be categorized into 2 groups of granulocytes (eosinophilic or basophilic) and 2 groups of agranulocytes (large or small) for performing a cytologic differential. The differential was not significantly altered by anticoagulant treatments providing cell morphology was adequate for obtaining a differential. Eosinophilic granulocytes predominated (59%) with fewer large agranulocytes (27%) and basophilic granulocytes (13%). Small agranulocytes comprised 2% of the total population. No single treatment provided an optimal method to evaluate freshwater mussel hemolymph. Maximal hemocyte counts were obtained following formalin treatment. l-cysteine reduced clumping and maintained hemocyte morphology for performing a cytologic differential. These techniques provide a standardized approach for the hematologic evaluation of freshwater mussels.


[Right non recurrent laryngeal nerve during thyroid surgery: one case report].
A 56 years old female was admitted to our department with complaint of a painless cervical mass. Clinical feature:there was a painless mass above left lobe of thyroid gland, which was about 3.0 cm x 2.5 cm in size, and could move with swallowing action. B-mode ultrasound features: there was a solid mass in left lobe of thyroid gland, which was about 3.2 cm. Nodule was found in isthmus, accompanied with lymphadenovarix on the left neck possibly be MCA. fT3: 4.64 pmol/L, fT4:16.56 pmol/L,TSH:3.74 mIU/L, anti-TG:17.75 U/ml, anti-TPO:40.77 U/ml. Pathological result of the neoplasm: papillocarcinoma. Clinical diagnosis: papillary thyroid carcinoma.


An abortive ligand-induced activation of CCR1-mediated downstream signaling event and a deficiency of CCR5 expression are associated with the hyporesponsiveness of human naive CD4+ T cells to CCL3 and CCL5.
Human memory CD4(+) T cells respond better to inflammatory CCLs/CC chemokines, CCL3 and CCL5, than naive CD4(+) T cells. We analyzed the regulatory mechanism underlying this difference. Memory and naive CD4(+) T cells expressed similarly high levels of CCR1; however, CCR5 was only expressed in memory CD4(+) T cells at low levels. Experiments using mAbs to block chemokine receptors revealed that CCR1 functioned as a major receptor for the binding of CCL5 in memory and naive CD4(+) T cells as well as the ligand-induced chemotaxis in memory CD4(+) T cells. Stimulation of memory CD4(+) T cells with CCL5 activated protein tyrosine kinase-dependent cascades, which were significantly blocked by anti-CCR1 mAb, whereas this stimulation failed to induce these events in naive CD4(+) T cells. Intracellular expressions of regulator of G protein signaling 3 and 4 were only detected in naive CD4(+) T cells. Pretreatment of cell membrane fractions from memory and naive CD4(+) T cells with GTP-gamma S inhibited CCL5 binding, indicating the involvement of G proteins in the interaction of CCL5 and its receptor(s). In contrast, CCL5 enhanced the GTP binding to G(i alpha) and G(q alpha) in memory CD4(+) T cells, but not in naive CD4(+) T cells. Thus, a failure of the ligand-induced activation of CCR1-mediated downstream signaling event as well as a deficiency of CCR5 expression may be involved in the hyporesponsiveness of naive CD4(+) T cells to CCL3 and CCL5.


Appropriateness of Telemedicine Versus In-Person Care: A Qualitative Exploration of Psychiatrists' Decision Making.
With widespread adoption of telemedicine in response to the COVID-19 pandemic, psychiatrists must determine which visits are best conducted via telemedicine versus in person. Although some telepsychiatry guidelines and best practices have been developed, the literature has not described how psychiatrists make decisions about offering different care modalities. The authors explored how psychiatrists decide whether telemedicine is appropriate for a given patient. From June 25 to August 4, 2021, the authors conducted semistructured interviews with 20 outpatient psychiatrists. The authors used a critical incident technique and clinical vignettes to identify conscious and unconscious factors that influence psychiatrists' decision to offer telemedicine. Using inductive thematic analysis, the authors analyzed interview data. Psychiatrists perceived that most patients are good candidates for telemedicine visits in the context of hybrid care models. Patient preference and situational factors, such as access to private spaces, rather than any particular diagnosis or patient demographic characteristic, drove telemedicine versus in-person care. Psychiatrists described numerous factors affecting their decision to offer telemedicine, and they were driven to try telemedicine and adjust as needed to "meet patients where they are" and to improve engagement in care. Psychiatrists reported using telemedicine as a bargaining chip in negotiations with patients, leveraging the offer of telemedicine to improve treatment attendance and adherence. This detailed assessment of how psychiatrists choose different care modalities can inform clinical practice guidelines and reimbursement policies that often mandate in-person visits. The results show that psychiatrists did not perceive intermittent in-person visits as essential for high-quality care.


The resin bond to high-translucent zirconia-A systematic review.
Several systematic literature reviews have assessed the scientific evidence on resin bonding protocols to conventional 3 mol% ytrria-stabilized zirconia (3Y-TZP) ceramics. It has been widely discussed, however, that the differing composition and physical properties of new high-translucent zirconia generations (4Y-TZP and 5Y-TZP) may require alternative bonding materials and procedures. This paper reviewed in vitro studies on the success and durability of bonding protocols to high-translucent zirconia. A systematic search of PubMed and Cochrane Library for in vitro studies on bonding to new zirconia generations published until November 2020 was conducted and complemented by a manual search. Studies selected for review fulfilled the applied inclusion and exclusion criteria. The quality of the included studies was assessed with the Cochrane risk-of-bias tool for randomized trials. Of 629 screened articles, 18 were included in this review. They investigated different surface pretreatment methods, primers, resin cements, aging procedures, and bond strength test protocols. The limited number of the identified studies and the heterogeneity of the extracted data did not allow to conduct a meta-analysis. The available evidence suggests that resin bonding protocols successfully applied to conventional zirconia are also the most successful for high-translucent zirconia. Airborne particle abrasion and special phosphate monomer-containing primers or composite resin cements provide long-term durable resin bonds. Durable bonds can be established between high-translucent zirconia and resin cements. The bonding materials and procedures applied do not compromise their physical properties.


Rating scales in depression: limitations and pitfalls.
Since the introduction of antidepressants to psychopharmacology in the 1960s, the Hamilton Depression Rating Scale (HAM-D) has been the most frequently used rating scale for depression. When used as a scale for prediction of outcome with antidepressants, the HAM-D, by its total score, has obtained limited use analogous to the Diagnostic and Statistical Manual of Mental Disorders. 4th ed (DSM-IV) diagnosis of major depression. Most research has been devoted to the use of the HAM-D to discriminate between placebo and active drugs or to show dose-response relationship in patients with major depression. An improvement in the total HAM-D score during a drug trial does not, however, in itself qualify the drug as an antidepressant, because the total score is not a sufficient statistic. The problem of statistical versus clinical significance when analyzing placebo-controlled trials, including dose-response relationship, is outlined, with the recommendation to use effect size statistics.


Effect of Nadir CD4+ T cell count on clinical measures of periodontal disease in HIV+ adults before and during immune reconstitution on HAART.
The contribution of HIV-infection to periodontal disease (PD) is poorly understood. We proposed that immunological markers would be associated with improved clinical measures of PD. We performed a longitudinal cohort study of HIV-infected adults who had started highly active antiretroviral therapy (HAART) <2 years. PD was characterized clinically as the percent of teeth with ≥ 1 site with periodontal probing depth (PPD) ≥ 5.0mm, recession (REC) >0mm, clinical attachment level (CAL) ≥ 4.0mm, and bleeding on probing (BOP) at ≥ 4 sites/tooth and microbiologically as specific periodontopathogen concentration. Linear mixed-effects models were used to assess the associations between immune function and PD. Forty (40) subjects with median 2.7 months on HAART and median nadir CD4+ T-cell count of 212 cells/μl completed a median 3 visits. Over 24 months, CD4+ T-cell count increased by a mean 173 cells/µl (p<0.001) and HIV RNA decreased by 0.5 log10 copies/ml (p<0.001); concurrently, PPD, CAL and BOP decreased by a mean 11.7%, 12.1%, and 14.7% respectively (all p<0.001). Lower nadir CD4+ T-cell count was associated with worse baseline REC (-6.72%; p=0.04) and CAL (9.06%; p<0.001). Further, lower nadir CD4+ T-cell count was associated with a greater relative longitudinal improvement in PPD in subjects with higher baseline levels of Porphyromonas gingivalis (p=0.027), and BOP in subjects with higher baseline levels of Porphyromonas gingivalis or Treponema denticola (p=0.001 and p=0.006 respectively). Longitudinal changes from baseline in CD4+ T-cell count and level of HIV RNA were not independently associated with longitudinal changes in any clinical markers of PD. Degree of immunosuppression was associated with baseline gingival recession. After HAART initiation, measures of active PD improved most in those with lower nadir CD4+ T-cell counts and higher baseline levels of specific periodontopathogens. Nadir CD4+ T-cell count differentially influences periodontal disease both before and after HAART in HIV-infected adults.


Presence of Escherichia coli O157:H7 in ground beef and ground baby beef meat.
A total of 114 beef and baby beef samples were examined. The samples included ground baby beef, mixed ground baby beef and pork, and chopped and shaped meat. The samples were analyzed from 30 different grocery stores in Zagreb, Croatia. The object of this study was to evaluate the prevalence of Escherichia coli O157:H7 in the samples that can enhance the potential risk of outbreaks of hemorrhagic colitis and hemolytic uremic syndrome. The results in all tested samples of E. coli O157:H7 were negative. A single sample was positive in a latex agglutination test using antiserum to O157:H7. It was identified as Proteus vulgaris at the Pasteur Institute, Paris, France. This result correlates positively with cross-contamination with Yersinia enterocolitica 09, Brucella abortus, Salmonella type N, and Pseudomonas maltophila.


Diabetes and the risk of acute urinary tract infection among postmenopausal women.
To examine whether the presence of diabetes alters the risk of acute urinary tract infection (UTI) in postmenopausal women. A case-control study of the Group Health Cooperative of Puget Sound (GHC), a staff-model nonprofit health maintenance organization in Washington State, was conducted. Subjects were women aged 55-75 years who had been members of GHC for at least 1 year and who had had an acute symptomatic UTI within the preceding month. Laboratory files were used to identify women with a urine culture that grew > or =10(5) colonies of a urinary pathogen. Medical records were reviewed to confirm the presence of acute, clinically symptomatic UTI. Control subjects were randomly selected from the GHC enrollment file, screened to remove women with recent UTI, and frequency matched to cases by age within 2 years. An interviewer ascertained self-reported clinician-diagnosed diabetes. Diagnosis of diabetes was confirmed by the GHC diabetes registry. A subsample of women underwent measurement of postvoid residual bladder volume (n = 748) and culture of vaginal flora (n = 454). Of the 901 case and 913 control subjects, diabetes was reported in 13.1 and 6.8%, respectively. The health plan diabetes registry confirmed the diagnosis in 92% of women who self-reported the condition. The age-adjusted odds ratio (OR) for UTI in relation to self-reported clinician-diagnosed diabetes was 2.2 (95% CI 1.6-3.0). Adjustment for frequency of sexual intercourse and history of UTI had little effect on this estimate. Compared with nondiabetic women, higher UTI odds were seen in subjects who used oral hypoglycemic agents (OR 2.9 [95% CI 1.7-5.1]) and insulin (2.6 [1.5-4.6]) but not in subjects with untreated diabetes or diabetes treated by lifestyle changes (1.3 [0.7-2.3]). No significant difference was seen in the OR for UTI in diabetic women with disease of shorter duration (<10 years, OR 1.9) or longer duration (> or =10 years, OR 2.6) or in relation to HbA(1c) level. Similar microbiologic pathogens were seen in diabetic and nondiabetic women. No significant differences were seen by diabetes status in mean postvoid residual bladder volume or vaginal flora. Diabetes under pharmacologic treatment is associated with increased risk of clinically apparent UTI in postmenopausal women.


Functional deletion of different Ly-1 T-cell-inducer subset activities by Ly-2 suppressor T lymphocytes.
T-suppressor-cell activity was analyzed by use of an intermediate culture system that allows the study of T-cell interactions in the absence of concomitant inducer effects on B cells. Activated suppressor T cells were incubated with their potential target cells [immune Ly-1+,Ly-2- (Ly-1) cells] for 24-48 hr, and then the Ly-1 cells were reisolated by removing the suppressor cells with an appropriate antiserum (Ly-2). The functional consequences of the interactions that occurred during the incubation period were then assessed. Suppressor cells deleted the functional activity of two inducer-T-cell subsets; the helper T cell, which induces B-cell production of antibody, and the T cell that induces Ly2+ T suppressor cells. This latter activity is more sensitive to suppression than is the former. As suppressor T cells inactivate the cells that are responsible for their activity (i.e., their specialized Ly-1 inducer cells), a form of negative regulation of suppressor-T-cell activity, in which the down regulation of suppressor cells is effected by their removal of their own inducer cells, can be postulated. In addition, these findings show that clonal deletion and active suppression need not be mutually exclusive mechanisms of immune unresponsiveness. Suppressor cells can produce a functional deletion of immune activity that persists after they themselves are removed, for example, by antisera, or in physiological situations by the negative form of regulation postulated.


Endoscopic diverticulotomy for symptomatic pediatric esophageal diverticula.
There have so far been few reports on esophageal diverticulum in children. We experienced two symptomatic pediatric cases with esophageal diverticulum. Our cases manifested high fever and dysphagia with chest pain during swallowing. The patients underwent endoscopic diverticulotomy. The septum between the diverticulum and the esophagus was cut using the argon plasma coagulation (APC 3000) system. We recommend an endoscopic diverticulotomy as an effective treatment modality for such symptomatic cases.


Formation of Nanoscale Protrusions on Polymer Films after Atomic Oxygen Irradiation: Changes in Morphologies, Masses, and FT-IR Spectra.
Atomic oxygen (AO) is the main component of the residual atmosphere in a low Earth orbit. AO with a translational energy of 5 eV colliding with artificial satellites forms nano- and microscale protrusions on polymeric materials. This study investigated the influences of AO (fluence and velocity distribution) and a polymer's chemical structure on such surface morphologies. The correlations between samples' mass losses and positions in the irradiation field of an AO beam were analyzed with polyimide (Kapton) films, a standard reference material for AO fluence measurements. The characterizations of polyethylene (PE), polypropylene (PP), and polystyrene (PS) films were studied using gel permeation chromatography and X-ray diffraction. The sample surfaces were observed using a field emission scanning electron microscope. Nanoscale protrusions were formed on all the samples and were larger but fewer with increasing AO fluence. The numerical density of protrusions formed on PE and PP was lower than that on PS. However, the erosion yields and functional groups of PE, PP, and PS were similar per FT-IR spectra.


Orbital (desmoid type) fibromatosis.
A case of extra-abdominal fibromatosis (EF) of the orbit is described in a 35-year-old man presenting with progressive exophthalmos, right ptosis and diplopia. MRI showed an orbital mass of intermediate signal in T1-weighted images (WI) and low signal in T2WI, which enhanced non-homogeneously after contrast injection. The histological diagnosis of EF was made and the lesion was surgically removed. No recurrence occurred in 40 months of follow-up.


Use of a Portable Inertial Measurement Unit as an Evaluation Method for Supraspinatus Muscle: Proposed Normative Values.
Treatment protocols do not specify an appropriate weight for rehabilitating the shoulder joint. The purpose of this study was to establish normative values for the shoulder abduction range of motion and recommended weights to be used in the rehabilitation process after injury to the supraspinatus muscle. Fifty-eight volunteers were assessed using the DyCare system. A test was conducted by lifting the arm to a 90° angle and having the participants lift different weights. The range of motion was similar for both sexes, suggesting that sex had no influence on this variable. Regarding the use of weights, men did not show as much stability in their movement execution, with a high dispersion seen in values between zero and three kilograms of weight, reaching a maximum weight of six kilograms. However, women showed good joint stability from the beginning of the test, with values that remained constant as weight increased up to a maximum of five kilograms. In conclusion, no major differences were observed in supraspinatus muscle injury recovery according to sex. However, differences were observed in the amount of weight that was necessary and appropriate to allow the participants to recover their muscular strength and avoid relapses.


'A Story of Being Invisible': A Single Case Study on the Significance of Being Recognised When Needing Acute Healthcare in the Early COVID-19 Pandemic.
Severe illness is often an existential threat that triggers emotions like fear, stress, and anxiousness. Such emotions can affect ill patients' encounters with healthcare personnel. We present a single case study of an older woman who contracted COVID-19 and her challenge to be recognised by healthcare personnel in the early pandemic. Storytelling is vital to understand how patients can create meaning in illness as it gives them the opportunity to reshape and restore their past and to project a future. We used Arthur Frank's dialogical narrative analysis to explore how one patient experienced her encounters with healthcare personnel. Although she felt very ill from COVID-19, she experienced being almost invisible and not being believed by healthcare personnel in a system marked by high stress levels and uncertainty. Despite rejections and illness, she managed to mobilise her resources, even though she depended on significant others. Her story brings forward altered self-understanding and growth. The importance of facilitating dialogical settings for healthcare professionals through patient storytelling also contributes to a broader societal understanding of illness beyond a biological perspective.


Engineering the structure and magnetic properties of crystalline solids via the metal-directed self-assembly of a versatile molecular building unit.
We report the supramolecular chemistry of several metal complexes of N-(4-pyridyl)benzamide (NPBA) with the general formula [Ma(NPBA)2AbSc], where M = Co2+, Ni2+, Zn2+, Mn2+, Cu2+, Ag+; A = NO3-, OAc-; S = MeOH, H2O; a = 0, 1, 2; b = 0, 1, 2, 4; and c = 0, 2. NPBA contains structural features that can engage in three modes of intermolecular interactions: (1) metal-ligand coordination, (2) hydrogen bonding, and (3) pi-pi stacking. NPBA forms one-dimensional (1-D) chains governed by hydrogen bonding, but when reacted with metal ions, it generates a wide variety of supramolecular scaffolds that control the arrangement of periodic nanostructures and form 1- (2-4), 2- (5), or 3-D (6-10) solid-state networks of hydrogen bonding and pi-pi stacking interactions in the crystal. Isostructural 7-9 exhibit a 2-D hydrogen bonding network that promotes topotaxial growth of single crystals of their isostructural family and generates crystal composites with two (11) and three (12) different components. Furthermore, 7-9 can also form crystalline solid solutions (M,M')(NPBA)2(NO3)2(MeOH)2 (M, M' = Co2+, Ni2+, or Zn2+, 13-16), where mixtures of Co2+, Ni2+, and Zn2+ share the same crystal lattice in different proportions to allow the formation of materials with modulated magnetic moments. Finally, we report the effects that multidimensional noncovalent networks exert on the magnetic moments between 2 and 300 K of 1-D (4), 2-D (5), and 3-D (7, 8, 10, and 13-16) paramagnetic networks.


Who is repeating anatomy? Trends in an undergraduate anatomy course.
Anatomy courses frequently serve as prerequisites or requirements for health sciences programs. Due to the challenging nature of anatomy, each semester there are students remediating the course (enrolled in the course for a second time), attempting to earn a grade competitive for admissions into a program of study. In this retrospective study, remediation rates and trends in an undergraduate anatomy course with over 400 students enrolled each semester at a large Midwestern university were identified. Demographic data was collected from spring 2004 to spring 2010, including students' age, ethnicity, major of study, class standing, college admission tests (ACT and SAT®) scores, anatomy laboratory and lecture examination scores, and final anatomy grades for each semester. Eleven percent of the students repeated the course at least once. Gender, ethnicity, major of study and SAT scores were all shown to be associated with whether or not a student would need to repeat the course. On average, students who repeated anatomy demonstrated significant improvements in lecture and laboratory scores when comparing first and second enrollments in anatomy, and therefore also saw improved final course grades in their second enrollment. These findings will aid future instructors to identify and assist at-risk students to succeed in anatomy. Instructors from other institutions may also find the results to be useful for identifying students at risk for struggling.


Fetal heart rate after epidural lidocaine and bupivacaine for elective cesarean section.
This prospective double-blind study was designed to determine whether the fetal heart rate (FHR) changes that have been reported after epidural administration of bupivacaine and lidocaine during labor are present when larger doses of these drugs are given during elective cesarean section. Prior to inserting an epidural catheter, FHR and maternal vital signs were monitored during a control period in 60 healthy term parturients. Patients were randomly assigned to receive either 0.5% bupivacaine with 0.1 mEq sodium bicarbonate added to each 20 ml (n = 30) or 2% lidocaine with 1:300,000 epinephrine (n = 30). A 3-ml test dose of the study solution was injected via the catheter and was followed by an additional 17 ml, in increments; additional doses were administered as necessary to obtain surgical anesthesia. FHR and maternal vital signs were monitored for at least 20 min and the characteristics of the anesthetic block noted. At delivery, neonatal status was evaluated, and maternal and cord blood samples were obtained for local anesthetic assays and neonatal blood gases. The groups were similar with respect to maternal characteristics, onset of surgical anesthesia, time to delivery, and uterine incision-delivery interval. Maternal blood pressure decreased from control values in both groups (P less than 0.05), but there was no difference between the groups in either the incidence of hypotension or ephedrine requirements. Analysis of FHR tracings by a perinatologist blinded to the study group revealed no changes after anesthesia and no significant differences between the groups at any time in basal FHR, short- or long-term variability, or the incidence of accelerations or decelerations.(ABSTRACT TRUNCATED AT 250 WORDS)


Computed tomography diagnosis of isolated splenic torsion in a dog.
Isolated splenic torsion in a dog was diagnosed using computed tomography (CT). The enlarged non enhanced spleen and a twisted soft tissue mass effect represented the rotated pedicle were the main findings. Abdominal radiography and ultrasonography were not conclusive.


Illuminating meaning and transforming issues of spirituality in HIV disease and AIDS: an application of Parse's theory of human becoming.
Although numerous supportive therapies are available to challenge human immunodeficiency virus (HIV) disease and acquired immunodeficiency syndrome (AIDS), no cure exists. Those with HIV disease and its sequelae must confront the reality of living with a complex, chronic illness. When addressing the many challenges associated with HIV disease and AIDS, individuals may experience issues associated with spirituality. The article synthesizes the concept of spirituality and identifies the possible issues associated with spirituality for individuals living with HIV disease and AIDS. Additionally, nursing strategies based on Parse's theory of human becoming are proposed.


Aberrant and alternative splicing in cancer.
Pre-mRNA splicing is a sophisticated and ubiquitous nuclear process, which is a natural source of cancer-causing errors in gene expression. Intronic splice site mutations of tumor suppressor genes often cause exon-skipping events that truncate proteins just like classical nonsense mutations. Also, many studies over the last 20 years have reported cancer-specific alternative splicing in the absence of genomic mutations. Affected proteins include transcription factors, cell signal transducers, and components of the extracellular matrix. Antibodies against alternatively spliced products on cancer cells are currently in clinical trials, and competitive reverse transcription-PCR across regions of alternative splicing is being used as a simple diagnostic test. As well as being associated with cancer, the nature of the alternative gene products is usually consistent with an active role in cancer; therefore, the alternative splicing process itself is a potential target for gene therapy.


Neonatal purpura fulminans secondary to group B streptococcal infection.
Purpura fulminans is an acute and frequently fatal disorder characterized by sudden onset of progressive cutaneous hemorrhage and necrosis due to dermal vascular thrombosis and disseminated intravascular coagulation. The authors present a neonate with extensive purpura fulminans due to group B streptoccoccal septicemia and evaluated the attributable clinical mortality and morbidity of this potentially lethal syndrome. Clinicians especially neonatologists should be aware that early-onset sepsis of group B Streptococcus in the newborn infant with purpura fulminans could be a cause of maternal carriage due to colonization of this pathogen microorganism.


Effects of chromaticities and occlusion of shaft on magnitude of the Müller-Lyer illusion.
The magnitude of the Müller-Lyer illusion was investigated using the Brentano figure by varying the chromaticities of the shaft and the fins along the cone-excitation axes and by varying the occlusion status of the shaft by the fins. 72 college students participated using the staircase method. The stimuli whose shaft and the fin chromaticities were the same produced larger illusions than stimuli with different chromaticities regardless of the luminance contrast between the figure and the surround. When the shaft appeared in front of the fins, the illusion effect was stronger than when the shaft was occluded by the fins.


Expression and clinical significance of SYNE1 and MAGI2 gene promoter methylation in gastric cancer.
Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related mortality globally. Abnormal DNA methylation is closely related to gastric cancer. The purpose of the study was to investigate the methylation of the SYNE1 and MAGI2 gene promoter and its relationship with the clinical-pathological factors, chemotherapy efficacy, and survival, thus providing a new biomarker for the prognosis and chemotherapy efficacy in gastric cancer.The methylation status of SYNE1 and MAGI2 in gastric cancer and adjacent tissues was detected by MSP method in 70 cases of advanced gastric cancer paraffin specimens.The methylation rate of the SYNE1 and MAGI2 gene promoter region was higher in gastric cancer tissues compared with adjacent tissues. The methylation status of SYNE1 was associated with the age at diagnosis and the size of the primary tumors, but no clinical or pathological factors have been found to be related with the methylation status of MAGI2 promoter. A high level of SYNE1 promoter methylation was associated with poorer chemotherapy efficacy in recurrent patients with gastric cancer. Thirty-three percent of the 70 patients exhibited highly methylated MAGI2; in this group, the median progression-free survival time was 4.1 months, shorter than those with negative methylated MAGI2 whose PFS was 5.1 months.MAGI2 is more methylated in gastric cancer than in adjacent tissues suggesting that hypermethylation changes in MAGI2 may be one of the mechanisms of tumorigenesis in gastric cancer. The methylation status of the SYNE1 and MAGI2 promoter regions may affect the chemotherapy efficacy of advanced gastric cancer. The prognosis of MAGI2-negative patients was better than that of positive ones, suggesting that MAGI2 may be an independent prognostic factor for PFS in patients with advanced gastric cancer.


Empathy and identification in Von Donnersmarck's The Lives of Others.
Florian Henckel von Donnersmarck's The Lives of Others, set in the German Democratic Republic in 1984, five years before the fall of the Berlin Wall, has been called the first accurate depiction of the psychological terror wielded by the Stasi, the East German secret police, who safeguarded the dictatorship of the proletariat. The film is about the psychological and political transformation of a Stasi officer, Wiesler, who undertakes the surveillance of a prominent playwright and his actress lover. The mechanisms through which Wiesler comes to empathize and identify with the subjects of his investigation, as he observes and listens in on the rich blend of passion, poetry, and politics that characterizes their lives, are explored in depth. Wiesler's transformation is based in part on the capacity to form implicit models of the behavior and experiences of others, based on the mirror neuron system, that Gallese and his colleagues call "embodied simulation." Underpinning the processes of empathy and identification so central to this film, embodied simulation is an unconscious and prereflexive mechanism through which the actions, emotions, and sensations we observe activate internal representations of the bodily and mental states of the other. Embodied simulation also expands our understanding of the power of the primal scene, which has long been identified as a major organizer of unconscious fantasies and conflicts throughout life, and which forms the central metaphor of the film. Embodied simulation scaffolds our aesthetic response to art, music, and literature, underlies the dynamics of spectatorship, and potentially catalyzes resistance to totalitarian mass movements.


Inhibition of Sphingosine Kinase Activity Enhances Immunogenic Cell Surface Exposure of Calreticulin Induced by the Synthetic Cannabinoid 5-epi-CP-55,940.
Background: Endogenous and synthetic cannabinoids have been shown to induce cancer cell death through the accumulation of the sphingolipid, ceramide (Cer). Recently, we have demonstrated that Cer accumulation enhances the induction of immunogenic cell death (ICD). Objectives: The primary objective of this study was to demonstrate that (±) 5-epi CP 55,940 (5-epi), a by-product of the chemical synthesis of the synthetic cannabinoid CP 55,940, induces ICD in colorectal cancer (CRC) cells, and that modulation of the sphingolipid metabolic pathway through inhibition of the sphingosine kinases (SphKs) enhances these effects. Methods: A cell culture model system of human CRC cell lines was employed to measure the cell surface and intracellular production of markers of ICD. The effects of 5-epi, alone and in combination with SphK inhibitors, on production of Cer through the de novo sphingolipid synthesis pathway were measured by Liquid Chromatography - Tandem Mass Spectrometry (LC/MS/MS)-based sphingolipidomic analysis. Cell surface exposure of calreticulin (ectoCRT), a hallmark of ICD, was measured by flow cytometry. Examination of the effects of 5-epi, alone and in combination with SphK inhibitors, on the intracellular signaling pathway associated with ICD was conducted by immunoblot analysis of human CRC cell lines. Results: Sphingolipidomic analysis indicated that 5-epi induces the de novo sphingolipid synthetic pathway. 5-epi dose dependently induces cell surface exposure of ectoCRT, and inhibition of Cer metabolism through inhibition of the SphKs significantly enhances 5-epi-induced ectoCRT exposure in multiple CRC cell lines. 5-epi induces and SphK inhibition enhances activation of the cell death signaling pathway associated with ICD. Conclusions: This study is the first demonstration that cannabinoids can induce the cell surface expression of ectoCRT, and potentially induce ICD. Moreover, this study reinforces our previous observation of a role for Cer accumulation in the induction of ICD and extends this observation to the cannabinoids, agents not typically associated with ICD. Inhibition of SphKs enhanced the 5-epi-induced signaling pathways leading to ICD and production of ectoCRT. Overexpression of SphK1 has previously been associated with chemotherapy resistance. Thus, targeting the SphKs has the potential to reverse chemotherapy resistance and simultaneously enhance the antitumor immune response through enhancement of ICD induction.


Synergistic enhancement of ethylene production and germination with kinetin and 1-aminocyclopropane-1-carboxylic Acid in lettuce seeds exposed to salinity stress.
Relief of salt (0.1 molar NaCl) stress on germination of lettuce (Lactuca sativa L., cv Mesa 659) seeds occurred with applications of 0.05 millimolar kinetin (KIN) and 1 to 10 millimolar 1-aminocyclopropane 1-carboxylic acid (ACC). Treatment with KIN enhanced the pregermination ethylene production under saline condition. A synergistic or an additive enhancement of pregermination ethylene production and germination occurred under saline condition in the presence of KIN and a saturating dose (10 millimolar) of ACC. No KIN-ACC synergism was noted in ethylene production or germination under nonsaline condition. Addition of 1 millimolar aminoethoxyvinylglycine (AVG) inhibited the KIN-enhanced pregermination ethylene production (85 to 89%) and germination (58%) under saline condition but not the synergistic effect of KIN + ACC on ethylene production. Under nonsaline condition, AVG had no effect on germination even though ethylene production was strongly inhibited. Alleviation of salt stress by KIN was inhibited in a competitive manner by 2,5-norbornadiene (NBD) (0.02-0.2 milliliter per liter), and the addition of ACC and/or ethylene reduced this inhibition. An increase in the pregermination ethylene production and germination occurred also by cotylenin E (CN) under saline condition. However, neither AVG (1 millimolar) nor NBD (0.02 to 0.2 milliliter per liter) prevented the relief of salt stress by CN. Thus, KIN may alleviate salt stress on germination by promoting both ACC production and its conversion to ethylene. Rapid utilization of ACC may be the basis for the synergistic or the additive effect of KIN plus ACC. The need for ethylene production and action for the relief of salt stress is circumvented by a treatment with CN.


Circular RNA Expression Profiling Identifies Glaucoma-Related Circular RNAs in Various Chronic Ocular Hypertension Rat Models.
Circular RNAs are characterized as a class of covalently closed circular RNA transcripts and are associated with a variety of cellular processes and neurological diseases by sponging microRNAs. Expression profiling of circular RNAs in glaucoma, which is a form of optic neuropathy, has not been performed to date. The most common characteristic of all forms of glaucoma is the loss of retinal ganglion cells. While the pathogenesis of glaucoma is not fully understood, intraocular pressure is unquestionably the only proven modifiable factor which makes chronic ocular hypertension (COH) animals the classical glaucoma models. Based on these findings, we completed the first in-depth study of rat retinal circular RNA expression profiling to identify probable biomarkers for the diagnosis of glaucoma. Two ocular hypertension models were induced by episcleral vein ligation (EVL) and microbead injection in rats. Overall, 15,819 circular RNA were detected. Furthermore, 3,502 differentially expressed circular RNAs verified in both COH rats were identified, of which 691 were upregulated and 2,811 were downregulated. Seven significantly downregulated (both log2FoldChange < -2.5 and adjusted P < 0.001) and seven significantly upregulated (both log2FoldChange > 2.5 and adjusted P < 0.001) circular RNAs were shown. Six target microRNAs aligned with the top 14 circular RNAs were identified. According to the construction of the circular RNA-microRNA network and circBase information, only RNO_CIRCpedia_1775 had the homologous hsa_circ_0023826 in the human genome. The hsa_circ_0023826 and mRNA of the host gene TENM4 (teneurin transmembrane protein 4) were validated in aqueous humor samples of five glaucoma patients and five cataract control patients. The expression of hsa_circ_0023826 showed a significant decrease in glaucoma patients, while TENM4 mRNA showed no significant difference compared to cataract patients (P = 0.024 and P = 0.294, respectively). The results of this study comprehensively characterized the expression profiles of circular RNA in glaucoma-affected eyes, as verified by two different ocular hypertension rat models. Together with the target microRNAs underlying the top differentially expressed circular RNAs, a new target of hsa_circ_0023826 and its host gene TENM4 were identified and further verified in the aqueous humor of glaucoma patients, indicating a promising biomarker for the disease.


Carbon nanotubes and microwaves: interactions, responses, and applications.
The interaction of microwaves with carbon nanotubes (CNTs) is an interesting topic for a variety of potential applications. Microwaves have been used for the purification of CNTs and for their chemical functionalization, providing a technique for simple, green, and large-scale protocols. In addition, the selective destruction of metallic CNTs under microwave irradiation could potentially result in a batch of semiconducting-only nanotubes. As an innovative application, the combination of microwaves with well-aligned CNTs could produce a new illumination technology. Moreover, the microwave absorbing properties of CNTs and their different behavior from typical organic compounds may open the door to the preparation of a wide range of new materials useful in many fields. A few examples of practical applications include electromagnetic interference for protecting the environment from radiation and microwave hyperthermia for cancer treatment as well as other medical therapies requiring precise heating of biological tissues.


Leakage of macromolecules in ventilated and unventilated segments of preterm lamb lungs.
The movement of macromolecules into and out of unventilated lung segments was evaluated in prematurely delivered and ventilated lambs. Seven lambs at 130 days gestational age had a bronchial balloon placed at birth before the first breath to obstruct the left lower lobe. Surfactant and 131I-albumin were instilled into the left lower lobe while surfactant and 125I-albumin were instilled into the remaining lung, and 70,000 molecular weight [3H]dextran was given into the vascular space at birth. Twenty-five percent of the lung by weight was not ventilated, and 24% of the total leak of dextran from the vascular space was recovered in the unventilated lungs at 3 h. An epithelial leak of protein from the two lung regions was documented by the loss of 11.4 and 18.4% of the labeled albumins in the nonventilated and ventilated lung regions, the appearance of 4.9 and 7.5% of the airway-instilled albumin in the vascular space from the nonventilated and ventilated lung regions, and the recovery of the labeled albumins in the carcasses of the lambs. The bidirectional flux of macromolecules was larger in the ventilated than in the nonventilated lung regions, indicating that ventilation can increase the leak of protein in the preterm lung. The lung areas that were never exposed to ventilation or oxygen also demonstrated a large bidirectional flux of macromolecules, a finding not present in the fetus, fullterm newborn, or adult. These findings indicate that ventilation is not solely responsible for the increased protein leak found in preterm lungs.(ABSTRACT TRUNCATED AT 250 WORDS)


Association Between Sensory Loss and Falls Among Middle-Aged and Older Chinese Population: Cross-Sectional and Longitudinal Analyses.
Introduction: Previous studies have suggested that sensory loss is linked to falls. However, most of these studies were cross-sectional designed, focused on single sensory loss, and were conducted in developed countries with mixed results. The current study aims to investigate the longitudinal relationship between hearing loss (HL), vision loss (VL) and dual sensory loss (DSL) with falls among middle-aged and older Chinese population over 7 years. Methods: The data was obtained from the China Health and Retirement Longitudinal Survey (CHARLS). In total, 7,623 Chinese older adults aged over 45 were included at baseline 2011 in this study. Self-reported falls and HL/VL/DSL were accepted. Other confounding variables included age, sex, BMI, educational level, marital status, various physical disorders and lifestyles. The impact of baseline sensory status on baseline prevalence of falls and incident falls over 7 years were assessed using logistic regression analyses. A logistic mixed model was used to assess the association between time-varying sensory loss with incident falls over 7 years after adjusted with multi-confounding factors. Results: Single and dual sensory loss groups had significantly higher prevalence of falls compared to no sensory loss (NSL) group (DSL: 22.4%, HL: 17.4%, VL: 15.7%, NSL: 12.3%). Baseline HL (OR: 1.503, 95% CI: 1.240-1.820), VL (OR: 1.330, 95% CI: 1.075-1.646) and DSL (OR: 2.061, 95% CI: 1.768-2.404) were significantly associated with prevalence of falls. For longitudinal observation over 7 years, baseline HL/DSL and persistence of all types of sensory loss were associated with incidence of falls. Time-varying HL (OR: 1.203, 95% CI: 1.070-1.354) and DSL (OR: 1.479, 95% CI: 1.343-1.629) were associated with incident falls after adjusted with multi-confounders, while VL was not. Conclusion: HL and DSL are significantly associated with both onset and increased incidence of falls over 7 year's observation in middle-aged and elderly Chinese population. Persistence or amelioration of sensory loss status could exert divergent influences on incidence of falls, which should be considered in the development of falls-prevention public health policies for aging population.


Utilising the EGFR interactome to identify mechanisms of drug resistance in non-small cell lung cancer - Proof of concept towards a systems pharmacology approach.
Drug treatment of epidermal growth factor receptor (EGFR) positive non-small cell lung cancer has improved substantially by targeting activating mutations within the receptor tyrosine kinase domain. However, the development of drug resistance still limits this approach. As root causes, large heterogeneity between tumour entities but also within tumour cells have been suggested. Therefore, approaches to identify these multitude and complex mechanisms are urgently required. Affinity purification coupled with high resolution mass spectrometry was applied to isolate and characterise the EGFR interactome from HCC4006 non-small cell lung cancer cells and their variant HCC4006rERLO0.5 adapted to grow in the presence of therapeutically relevant concentrations of erlotinib. Bioinformatics analyses were carried out to identify proteins and their related molecular functions that interact differentially with EGFR in the untreated state or when incubated with erlotinib prior to EGFR activation. Across all experimental conditions 375 proteins were detected to participate in the EGFR interactome, 90% of which constituted a complex protein interaction network that was bioinformatically reconstructed from literature data. Treatment of HCC4006rERLO0.5 cells carrying a resistance phenotype to erlotinib was associated with an increase of protein levels of members of the clathrin-associated adaptor protein family AP2 (AP2A1, AP2A2, AP2B1), structural proteins of cytoskeleton rearrangement as well as signalling molecules such as Shc. Validation experiments confirmed activation of the Ras-Raf-Mek-Erk (MAPK)-pathway, of which Shc is an initiating adaptor molecule, in HCC4006rERLO0.5 cells. Taken together, differential proteins in the EGFR interactome of HCC4006rERLO0.5 cells were identified that could be related to multiple resistance mechanisms including alterations in growth factor receptor expression, cellular remodelling processes suggesting epithelial-to-mesenchymal transition as well as alterations in downstream signalling. Knowledge of these mechanisms is a pivotal step to build an integrative model of drug resistance in a systems pharmacology manner and to be able to investigate the interplay of these mechanisms and ultimately recommend combinatorial treatment strategies to overcome drug resistance.


Effect of alginate encapsulation on the cellular transcriptome of human islets.
Encapsulation of human islets may prevent their immune rejection when transplanted into diabetic recipients. To assist in understanding why clinical outcomes with encapsulated islets were not ideal, we examined the effect of encapsulation on their global gene (mRNA) and selected miRNAs (non-coding (nc)RNA) expression. For functional studies, encapsulated islets were transplanted into peritoneal cavity of diabetic NOD-SCID mice. Genomics analysis and transplantation studies demonstrate that islet origin and isolation centres are a major source of variation in islet quality. In contrast, tissue culture and the encapsulation process had only a minimal effect, and did not affect islet viability. Microarray analysis showed that as few as 29 genes were up-regulated and 2 genes down-regulated (cut-off threshold 0.1) by encapsulation. Ingenuity analysis showed that up-regulated genes were involved mostly in inflammation, especially chemotaxis, and vascularisation. However, protein expression of these factors was not altered by encapsulation, raising doubts about the biosignificance of the gene changes. Encapsulation had no effect on levels of islet miRNAs. In vivo studies indicate differences among the centres in the quality of the islets isolated. We conclude that microencapsulation of human islets with barium alginate has little effect on their transcriptome.


Temporal dissection of tumorigenesis in primary cancers.
Timely intervention for cancer requires knowledge of its earliest genetic aberrations. Sequencing of tumors and their metastases reveals numerous abnormalities occurring late in progression. A means to temporally order aberrations in a single cancer, rather than inferring them from serially acquired samples, would define changes preceding even clinically evident disease. We integrate DNA sequence and copy number information to reconstruct the order of abnormalities as individual tumors evolve for 2 separate cancer types. We detect vast, unreported expansion of simple mutations sharply demarcated by recombinative loss of the second copy of TP53 in cutaneous squamous cell carcinomas (cSCC) and serous ovarian adenocarcinomas, in the former surpassing 50 mutations per megabase. In cSCCs, we also report diverse secondary mutations in known and novel oncogenic pathways, illustrating how such expanded mutagenesis directly promotes malignant progression. These results reframe paradigms in which TP53 mutation is required later, to bypass senescence induced by driver oncogenes.


Invited article: in situ comparison of passive radon-thoron discriminative monitors at subsurface workplaces in Hungary.
During a one-year long measurement period, radon and thoron data obtained by two different passive radon-thoron discriminative monitors were compared at subsurface workplaces in Hungary, such as mines (bauxite and manganese ore) and caves (medical and touristic). These workplaces have special environmental conditions, such as, stable and high relative humidity (100%), relatively stable temperature (12°C-21°C), low or high wind speed (max. 2.4 m s(-1)) and low or elevated aerosol concentration (130-60,000 particles m(-3)). The measured radon and thoron concentrations fluctuated in a wide range among the different workplaces. The respective annual average radon concentrations and their standard deviations (in brackets) measured by the passive radon-thoron discriminative monitor with cellulose filter (CF) and the passive radon-thoron discriminative monitor with sponge filter (SF) were: 350(321) Bq m(-3) and 550(497) Bq m(-3) in the bauxite mine; 887(604) Bq m(-3) and 1258(788) Bq m(-3) in the manganese ore mine; 2510(2341) Bq m(-3) and 3403(3075) Bq m(-3) in the medical cave (Hospital Cave of Tapolca); and 6239(2057) Bq m(-3) and 8512(1955) Bq m(-3) in the touristic cave (Lake Cave of Tapolca). The respective average thoron concentrations and their standard deviation (in brackets) measured by CF and SF monitors were: 154(210) Bq m(-3) and 161(148) Bq m(-3) in the bauxite mine; 187(191) Bq m(-3) and 117(147) Bq m(-3) in the manganese-ore mine; 360(524) Bq m(-3) and 371(789) Bq m(-3) in the medical cave (Hospital Cave of Tapolca); and 1420(1184) Bq m(-3) and 1462(3655) Bq m(-3) in the touristic cave (Lake Cave of Tapolca). Under these circumstances, comparison of the radon data for the SF and CF monitors showed the former were consistently 51% higher in the bauxite mine, 38% higher in the manganese ore mine, and 34% higher in the caves. Consequently, correction is required on previously obtained radon data acquired by CF monitors at subsurface workplaces to gain comparable data for SF monitors. In the case of thoron, the data were unreliable and no significant tendency was seen during the comparison therefore comparison of previously obtained thoron data acquired by either CF or SF is doubtful. There was probable influence by relative humidity on the detection response; however, the effects of the high wind speed and elevated aerosol concentration could not be excluded. The results of this study call attention to the importance of calibration under extreme environmental conditions and the need for using reliable radon-thoron monitors for subsurface workplaces.


What is the hair cell transduction channel?
In contrast to nearly all other sensory systems, the mechanically sensitive ion channel carrying the receptor current into hair cells of the inner ear has not been identified in molecular terms. A number of candidates from at least two different ion channel families have been considered: these include the epithelial sodium channel (ENaC) and acid-sensing ion channel (ASIC) members of the DEG/ENaC superfamily of amiloride-sensitive sodium channels, as well as the TRP channels TRPN1, TRPV4, TRPML3 and TRPA1. For each, initial supportive results were followed by further studies that cast doubts on their involvement. No promising candidates have recently emerged, but the TRP family continues to be attractive in general.