Dephospho-dynamin 1 coupled to activity-dependent bulk endocytosis participates in epileptic seizure in primary hippocampal neurons.
Epilepsy is a severe neurological and mental disorder, and not all patients adequately respond to the current treatments. Dynamin 1 plays a key role in synaptic endocytosis and the modulation of neurological function. Cultured hippocampal neurons were used in the study. First, the viability of neurons was determined by the CCK-8 assay after culturing in magnesium-free medium, DMSO, dynasore (dynamin agonist), and PIP2 (dynamin antagonist). Then, the effect of dynasore on seizure activity was evaluated. Next, we tested the levels of phospho-dynamin 1/total dynamin 1 and dynamin 1 mRNA in the control group and four epilepsy groups. Moreover, the uptake of tetramethylrhodamine-dextran in the different groups was measured. Dephospho-dynamin 1 expression was significantly increased in hyperexcitable neurons, while there was no change in total dynamin 1 level. The level of dephospho-dynamin 1 in hyperexcitable neurons was reduced when cultured with dynasore but increased with PIP2 treatment. Activity-dependent bulk endocytosis (ADBE) was upregulated in hyperexcitable neurons. Along with a decrease in dephospho-dynamin 1 level, ADBE was also downregulated with dynasore treatment, while PIP2 did not affect ABDE. The close link between the dephosphorylation status of dynamin 1 and ADBE suggests that ADBE activation depends on dynamin 1 dephosphorylation. Dephospho-dynamin 1 triggers ADBE to meet the requirements of high-frequency discharges during epileptic seizures.


Aerobic dynamic feeding as a strategy for in situ accumulation of polyhydroxyalkanoate in aerobic granules.
Aerobic dynamic feeding (ADF) strategy was applied in sequencing batch reactor (SBR) to accumulate polyhydroxyalkanoate (PHA) in aerobic granules. The aerobic granules were able to remove 90% of the COD from palm oil mill effluent (POME). The volatile fatty acids (VFAs) in the POME are the sole source of the PHA accumulation. In this work, 100% removal of propionic and butyric acids in the POME were observed. The highest amount of PHA produced in aerobic granules was 0.6833mgPHA/mgbiomass. The PHA formed was identified as a P (hydroxybutyrate-co-hydroxyvalerate) P (HB-co-HV).


Long-term survival of patients with malignant ventricular arrhythmia treated with antiarrhythmic drugs.
The protective effect of antiarrhythmic agents for patients with malignant ventricular arrhythmia (defined as noninfarction ventricular fibrillation or sustained hemodynamically compromising ventricular tachycardia) remains uncertain. We have analyzed survival among 123 such patients (98 males, 25 females, average age 53.6 years) dependent on the abolition of antiarrhythmic drugs of salvos of ventricular tachycardia and R-on-T ventricular premature beats (Lown grades 4B and 5). Over an average follow-up of 29.6 months there were 35 deaths (11.2 percent annual mortality rate) of whom 23 patients succumbed suddenly (8.2 percent annual mortality rate). Among 98 patients in whom antiarrhythmic drugs abolished grades 4B and 5 ventricular premature beats, only 6 sudden deaths occurred for a 2.3 percent annual mortality rate. Of the 25 patients in whom advanced ventricular premature beats were not controlled, 17 died suddenly. Seventy-nine patients had left ventricular studies suitable for analysis. Among 44 patients with left ventricular dysfunction, control of ventricular premature beats was a critical element predicting survival. The annual sudden death rate for the 12 noncontrolled patients with left ventricular dysfunction was 41 percent contrasting with only 3.1 percent for the 32 patients with similar abnormalities in ventricular function in whom advanced ventricular premature beats were abolished. It is concluded that antiarrhythmic drugs can protect against the recurrence of life-threatening arrhythmias in patients who have manifest ventricular fibrillation or ventricular tachycardia and that abolition of certain advanced grades of ventricular premature beats provides an effective therapeutic objective.


Nuclear magnetic resonance titration curves of histidine ring protons. The effect of temperature on ribonuclease A.
The ionization constants of 3 of the histidine residues of ribonuclease A have beenobtained at 5 temperatures from the nuclear magnetic resonance titration curves of the imidazole C2 proton resonances. Thermodynamic parameters derived from the ionization constants indicate that histidine residues 105 and 119 are fairly well exposed to solvent, while histidine residue 12 is in a somewhat more restricted environment. Measurements of the low pH inflection present in the titration curve of histidine-12 yield a large negative entropy value, indicating that the group givine rise to this inflection is also buried.


Porcine dermal collagen mesh (Permacol™) as a bioprosthesis in the ligation of intersphincteric tract (BioLIFT) procedure.
Ligation of intersphincteric tract (LIFT) is a sphincter-saving technique used to treat anal fistulas. Incorporation of a bioprosthesis in LIFT (BioLIFT) aims to improve healing. The use of cross-linked porcine dermal collagen mesh Permacol™ in BioLIFT has never been investigated. The aim of this study was to compare the healing rates and outcome of LIFT and BioLIFT for complex anal fistulas using the Permacol™ biological mesh. A retrospective analysis of all patients having LIFT or BioLIFT for complex fistulas from January 2010 to November 2019 was performed in a tertiary referral centre. Patient data from a prospectively collected database of all patients having LIFT or BioLIFT were analyzed. LIFT and BioLIFT were performed in 48 (82.8%) and 10 (17.2%) patients, respectively. All BioLIFT patients had previous interventions for their fistulas compared to 30 (62.5%) of patients who had LIFT, p = 0.023. The primary healing rate for LIFT was 87.5% (42/48) compared to 80% (8/10) in BioLIFT, (p = 0.42). Eight (13.8%) patients developed complications, 6 (12.5%) in the LIFT group vs 2 (20%) in the BioLIFT group (p = 0.62). On univariate analysis, the number of previous operations was predictive of complications (p = 0.03). BioLIFT was not associated with complication (OR = 1.75, 95% CI: 0.30-10.3, p = 0.54) or primary healing (OR = 0.57, 95% CI: 0.97-3.36, p = 0.54). There was no significant difference in recurrence (LIFT 12.5% vs BioLIFT 0%, p = 0.58). Kaplan-Meier analysis found no difference in time to recurrence between the two groups (p = 0.65). Permacol™ mesh in BioLIFT is feasible and achieves a high primary healing rate of 80%. Prospective evidence is needed to establish the benefits of BioLIFT and determine whether Permacol™ is superior to the non-cross-linked porcine submucosal mesh.


Quality of life in children with vesicoureteral reflux.
Vesicoureteral reflux (VUR) is commonly diagnosed in children presenting with urinary tract infections. Antibiotic prophylaxis and ureteric surgery are standard treatments for these children. Our aim was to investigate whether health-related quality of life (HRQOL) was altered in children treated for VUR. Children aged 1-5 years with grade III or higher VUR were identified through electronic records at the Stollery Children's Hospital. Parents of these children were mailed the TNO-AZL Netherlands Organisation for Applied Scientific Research Academic Medical Centre Quality of Life (TAPQOL) questionnaire. QOL scores for this group were compared with normative controls from the instrument's creators using the Mann-Whitney U test. Thirty-two of the 96 (33%) mailed surveys were returned. Eight children had surgery, and 19 were treated with antibiotic prophylaxis. When comparing the VUR group with the control group, we found that anxiety and social functioning scores were significantly better in patients with VUR (p < 0.01). The VUR group had worse scores in problem behavior, stomach complaints ,and communication (p < 0.01). This study reveals that children with VUR have a reasonable QOL when compared with controls. However, the diagnosis of VUR and its management does have an impact on gastrointestinal complaints, behavior, and communication, which may occur as a result of chronic medical intervention.


Perioperative Incidence of Venous Thromboembolism in Patients With Ovarian Cancer Using Four Different Data Collection Methods: A Manitoba Ovarian Cancer Outcomes (MOCO) Group Study.
To evaluate the incidence of venous thromboembolism (VTE) in 90-day pre-operative period and at 30 and 90 days post surgery in patients who underwent debulking for ovarian cancer, analyze the impact of extended prophylaxis that was initiated in 2012, and examine the influence of data collection technique on reported rates of VTE. This retrospective database and records study examined rates of VTE in epithelial ovarian cancer patients in Manitoba, Canada between 2004 and 2016. Cases of VTE were identified using ICD codes, drug prescriptions, and records reviews; 4 different data collection methods were used. Analysis was performed with analysis of variance, Kruskal-Wallis and χ2 tests, and interrupted time series models. Data collection identified 823 debulking surgeries, with a final cohort of 779 patients; data were analyzed before and after extended prophylaxis intervention. Overall rates of VTE varied by collection method and were 1.82%-5.47%, 0.36%-3.16%, 0.85%-1.46%, and 1.46%-2.79%, respectively. During this timeframe, we noted a significant increase in the use of neoadjuvant chemotherapy (P = 0.010) and stage migration to stage 3 (P < 0.001). We report the rates of VTE utilizing 4 different data collection methods. We found a low overall rate, with some trends requiring further investigation. This study highlights the importance of data collection method on the reported rates of VTE in research.


[Central venous catheterization with an incorporated J-wire and contamination protective sleeves for rapid venous catheterization of the external jugular vein].
The external jugular vein can easily be identified in most patients and provides an alternative access to the superior vena cava. Unfortunately, advancement of the catheter may be hampered for anatomical reasons, e.g. the presence of valves. Use of a flexible guide-wire with curved tip (J-wire), as first proposed by Blitt et al., results in a significant increase in the rate of successful cannulations. This method necessitates tedious surgical draping, however, that may not always be practicable. Therefore, a catheter was developed that is wrapped in a protective sleeve and contains a J-wire instead of the common plastic mandrin, thus making contamination during insertion impossible.


Methodological aspects of a serodiagnostic Clostridium tumour test--experience with spontaneous canine tumours.
The paper describes the development of appropriate antigen and method combinations for the microbiological cancer test using the non-oncolysing strain Clostridium butyricum CNRZ 528 in dogs with spontaneous tumours. The diagnostic rod antibodies could be determined quantitatively by the complement fixation test if a short-time warm fixation and a long-time cold fixation procedure were combined in separate runs and if two different antigens, a rod corpuscular antigen and a rod surface antigen, were used. Since complement-fixing antibodies were not always detected in cases of malignant tumours, we additionally used the passive haemagglutination method after pre-absorbing the sera with cross-reacting clostridial antigens. The efficiency of the microbiological cancer test could not be substantially increased, however, by the method combination the reliability of the evaluation of low seropositive titres was improved.


Pipette tip dummy molecularly imprinted solid-phase extraction of Bisphenol A from urine samples and analysis by gas chromatography coupled to mass spectrometry.
Molecularly imprinted polymers (MIPs) were synthesized and used as sorbent for Bisphenol A (BPA) pipette tip solid-phase microextraction from urine samples and BPA analysis by gas chromatography coupled to mass spectrometry (GC-MS). The MIPs were synthesized by the sol-gel methodology. Aminopropyltriethoxysilane (APTES) and tetraethyl orthosilicate (TEOS) were used as functional monomer and cross-linking reagent, respectively. BPA and tetrabromobisphenol A (TBBPA) were evaluated as template during MIP synthesis. The BPA-based MIP displayed slightly higher extraction efficiency than the TBBPA-based dummy molecularly imprinted polymer (DMIP), but the TBBPA-based DMIP was selected as sorbent to minimize interference from leaked template. Comparison of the TBBPA-based DMIP, BPA-based MIP, and non-imprinted polymer (NIP) extraction efficiencies attested that the TBBPA-based DMIP was selective. The synthesized polymers were characterized by Scanning Electron Microscopy (SEM) and Fourier Transform Infrared spectroscopy (FTIR). The TBBPA-based DMIP was reused for over 100 times, which confirmed its robustness. The developed method was linear from 50 to 500ngmL-1. Precision values had coefficient of variation (CV) ranging from 4 to 14%. The accuracy relative standard deviation values (RSD) varied from -13.6 to 12.3%.


A STUDY TO ASCERTAIN THE ADEQUACY OF OBSERVANCE OF UNIVERSAL PRECAUTIONS IN ACUTE MEDICAL AND SURGICAL WARDS OF A LARGE TEACHING HOSPITAL.
The present study was a cross-sectional analytic epidemiological design to assess the frequency of observance of universal precautions in acute care wards of a large teaching hospital and to assess the epidemiological determinants of such observance. A total population of medical officers, nurses, paramedical and ancillary workers working in acute medical and surgical wards was studied using direct observations recorded on a pre-tested, structured format. The study revealed that handwashing was more frequently practiced by medical officers and ancillary staff (68% to 93%) as compared to nurses and paramedicals (38% to 58%) (p<0.01). Significantly higher proportion of medical officers in medical wards (93%) and nurses (63.3%) and ancillary workers in surgical ward (89%) were practicing handwashing (p<0.01). The practice of usage of gloves was significantly more frequent among medical officers and ancillary workers (72% to 100%) while it was quite inadequate among nurses and paramedicals (28% to 36%), (p<0.001). However, use of gloves was significantly better among nurses in surgical ward and paramedicals in medical ward (p<0.05). A linear trend analysis of the use of protective clothing revealed that the odds of nurses adequately using the same were much lower while those of ancillary workers were much higher as compared to medical officers, the trend being highly significant in both the type of wards (p<0.001). The study reveals a definite need of stepping up educational and motivational methods for observance of universal precautions by health care workers in large teaching hospitals. In particular, nurses and paramedical workers have been identified as high risk groups, needing concerted efforts for observing these precautions.


A 5-year prospective cohort study on health-related quality of life in patients with narcolepsy.
To evaluate the 5-year variation of health-related quality of life (HRQoL) and mood symptoms in a cohort of patients with narcolepsy. Adults attending the Sleep Centre of the Department of Neurological Sciences, University of Bologna in 1997 and meeting the International Classification of Sleep Disorders-Revised criteria for the diagnosis of narcolepsy were eligible. Included patients self-administered the Medical Outcome Short Form-36 (SF-36) and the Zung depression scale (ZDS) prospectively in 1998 and 2003. There was no significant difference between 1998 and 2003 measures of SF-36 and ZDS in the 54 patients included. About 25% of them showed moderate or severe mood symptoms in both observations. ZDS score (inversely) and duration of disease (directly) explained a percentage of variance of role physical, vitality (VT), social functioning (SF) and role emotional. At the second observation VT and SF had a further percentage of variance explained by excessive daytime sleepiness (EDS) and age at onset. Self-reported diabetes frequency doubled after 5 years (from 7% to 17%). Patients with narcolepsy show a stable impairment of HRQoL in a 5-year period with respect to Italian normative data. Mood status and EDS negatively influence their HRQoL while disease duration has a positive influence.


Myelodysplastic syndrome after acute promyelocytic leukemia: the European APL group experience.
With improved treatment of acute promyelocytic leukemia (APL) by all trans retinoic acid (ATRA) combined to anthracycline-aracytin chemotherapy (CT), a larger number of those patients may be at risk of late complications. Recently, the Rome group reported five cases of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML, non-APL) occurring during the course of 77 APL patients (6.5%) in complete remission (CR). From 1991 to 1998, we treated 677 newly diagnosed cases of APL, and 617 of them achieved CR with ATRA combined to CT (n=579) or CT alone (n=38); 246 of them received subsequent maintenance CT with 6 mercaptopurine and methotrexate. With a median follow-up of 51 months, 6 patients (0.97%) developed MDS, 13-74 months after the diagnosis of APL. In all six cases, t(15;17) and PML-RARalpha rearrangement were absent at the time of MDS diagnosis, and karyotype mainly showed complex cytogenetic abnormalities involving chromosomes 5 and/or 7, typical of MDS observed after treatment with alkylating agents, although none of the six patients had received such agents for the treatment of APL. Our findings suggest that MDS can indeed be a long-term complication in APL, although probably at lower incidence than that previously reported.


Duration of focal complex, secondarily generalized tonic-clonic, and primarily generalized tonic-clonic seizures--A video-EEG analysis.
Identifying seizures with prolonged duration during video-electroencephalographic (EEG) monitoring is of importance to inform clinicians when to start emergency treatment of seizures to prevent status epilepticus. The aims of this study were to assess the clinical and EEG seizure duration (SD) in consecutive patients with epilepsy who underwent prolonged video-EEG monitoring and to identify a seizure type-dependent time point to start emergency treatment based on the likelihood that seizures will not stop spontaneously. Furthermore, we sought to determine predictors of SD and explored the relationship between antiepileptic drug (AED) serum levels and SD. We retrospectively analyzed 1796 seizures in 200 patients undergoing video-EEG monitoring between January 2006 and March 2008. Focal simple seizures lasted significantly shorter (clinical SD: 28s, EEG SD: 42 s) compared with focal complex seizures (clinical SD: 64 s, EEG SD: 62 s), and both seizure types lasted significantly shorter compared with secondarily generalized tonic-clonic seizures (GTCSs; clinical SD: 90 s, EEG SD: 96 s). There was no difference between the duration of the convulsive phase of primary GTCSs (defined as nonfocal) and that of secondarily GTCSs (each 65 s). Cumulative clinical SD (99%) was 7 min in focal complex seizures and 11 min in focal simple seizures. Mixed linear regression model demonstrated that history of status epilepticus (P = 0.034), temporal lobe seizure onset (P = 0.040), and MRI lesions (P = 0.013) were significantly associated with logarithmic EEG SD in focal epilepsies recorded with scalp electrodes. We found significant negative correlations between the AED serum level and the EEG SD in patients treated with monotherapy: carbamazepine (P < 0.001), levetiracetam (P = 0.001), oxcarbazepine (P = 0.001), and valproic acid (P = 0.038) but not with lamotrigine monotherapy and EEG SD. Based on the results of this study, we propose 2 min of convulsive seizure activity (irrespective of focal or generalized onset) as a prolonged seizure, which could serve as a time point to consider treatment to prevent status epilepticus. In focal complex seizures, we suggest an upper limit of 7 min, and in focal simple seizures 11 min, as definition of prolonged seizures. History of status epilepticus, temporal seizure onset, and lesional MRI findings are factors associated with significantly longer SD. Negative correlations of carbamazepine, levetiracetam, oxcarbazepine, and valproic acid serum levels and SD suggest a prolonging effect on seizures during withdrawal of these AEDs during video-EEG monitoring sessions. This article is part of a Special Issue entitled "Status Epilepticus".


Gymnemic acids inhibit rabbit glyceraldehyde-3-phosphate dehydrogenase and induce a smearing of its electrophoretic band and dephosphorylation.
Gymnemic acids (GA) inhibited rabbit muscle glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity. Binding of GA to GAPDH was observed by surface plasmon resonance measurement. Incubation of GAPDH with GA induced a smearing of the GAPDH band in SDS-PAGE. The GA-induced smearing was diminished by prior incubation of GA with gamma-cyclodextrin or by GA treatment with NAD. GA treatment did not affect the electrophoretic mobility of glucose-6-phosphate isomerase and dehydrogenase. GA treatment diminished the GAPDH band detected by an antibody to phosphoserine, but did not affect the phosphoserine bands of glucose-6-phosphate isomerase and dehydrogenase. These results indicated that GA specifically induced dephosphorylation of GAPDH.


The Christaller's Formation Mechanism for the Ordered Nanopores of Anodic Alumina Template.
The highly ordered alumina pores were prepared via a two-step anodic oxidation process in the electrolyte of oxalic acid. Five different formation mechanisms of the alumina nanopores are summarized. On the basis of those models, combined with the Christaller's central place theory, a Christaller's formation mechanism of the alumina nanopores is proposed for the first time. It is the mechanical stresses between those pores during the corrosion expansion process that determines the morphology of alumina pores. Anodic oxidation time is too longer, the regular arrangements of pores will be damaged. This mechanism will provide the model analysis and reference value for studies of the formation mechanisms of alumina nanopores.


Age differences in adaptation of medial-lateral gait parameters during split-belt treadmill walking.
The split-belt treadmill has been used to examine the adaptation of spatial and temporal gait parameters. Historically, similar studies have focused on anterior-posterior (AP) spatiotemporal gait parameters because this paradigm is primarily a perturbation in the AP direction, but it is important to understand whether and how medial-lateral (ML) control adapts in this scenario. The ML control of balance must be actively controlled and adapted in different walking environments. Furthermore, it is well established that older adults have balance difficulties. Therefore, we seek to determine whether ML balance adaptation differs in older age. We analyzed split belt induced changes in gait parameters including variables which inform us about ML balance control in younger and older adults. Our primary finding is that younger adults showed sustained asymmetric changes in these ML balance parameters during the split condition. Specifically, younger adults sustained a greater displacement between their fast stance foot and their upper body, relative to the slow stance foot, in the ML direction. This finding suggests that younger adults may be exploiting passive dynamics in the ML direction, which may be more metabolically efficient. Older adults did not display the same degree of asymmetry, suggesting older adults may be more concerned about maintaining a stable gait.


A study on the nutritional status of adolescent girls.
One hundred and twenty school girls in the age group of 13-15 years from four Government schools of Ludhiana city were selected for the study. On the basis of their family income they were divided into three experimental groups i.e. income group I (IgI), income group II (IgII) and income group III (IgIII). The results showed that the intake was low for all the foods. However, the consumption of fruits, milk and milk-products, sugar and jaggery, fats and oils by the subjects of IgII and IgIII was significantly higher (p < 0.05) than IgI. The mean daily intake of energy, protein, iron, calcium, vitamin A & vitamin C was inadequate while the intake of fibre was adequate by the subjects as compared to ICMR recommendations. There was no significant difference in energy, protein and iron intakes among the subjects of three groups. However, the fibre intake by the subjects of IgI was significantly higher (p < 0.05) than the subjects of IgIII, whereas the intake of calcium, vitamin A and ascorbic acid by the subjects of IgII & IgIII was significantly higher (p < 0.05) than those of IgI. The average body weights and heights of the subjects were normal. The haemoglobin (Hb) level of the subjects ranged from 8.5-12.5 g/dl with a mean value of 10.73 + 0.07 and reported that only 23 percent of the subjects had acceptable level.


The effects of cement thickness and cement shade on the final color of lithium disilicate crowns.
The aim of this study is to evaluate the effect of resin cement color, cement thickness, and thermocycling on the final color of monolithic lithium disilicate crowns. A total of ninety prepared central incisors of typodont teeth were restored with lithium disilicate crowns which have different cement thicknesses (40 µm, 80 µm, and 120 µm) and cement shades (clear, yellow, and white). Color parameters of restorations were measured with a spectrophotometer in three different steps 1) before cementing 2) after cementing and 3) after thermocycling with 10000 cycles. Color differences (ΔE00) were calculated with the CIEDE2000 formula and evaluated according to perceptibility (0.8) and acceptability (1.8) thresholds. The ΔE00 data were analyzed by using two-way ANOVA before and after thermocycling (α = .05). There was no interaction between the cement shade and the cement thickness factors. After cementation, the mean ΔE00 was under the perceptibility threshold in the group of 40 µm cement thickness and clear cement while it was between the perceptibility and acceptability thresholds (0.8 < ΔE00 < 1.8) for all other groups. After thermocycling, the ΔE00 values were between the perceptibility and acceptability thresholds for all experimental groups. Although there were no significant differences among the groups, thermocycling increased the color difference values. The cementation of restorations with clear, yellow, and white resin cements resulted in color differences with uncemented restorations except for the group cemented with clear cement in 40 µm cement thickness. All study groups revealed perceptible color change after thermocycling.


Responses to catecholamines of the rat isolated uterus throughout the natural oestrous cycle.
The effects of noradrenaline (NA), adrenaline (Adr) and isoprenaline (Iso) on rat isolated uterus were studied, throughout the natural oestrous cycle. The beta-inhibitory effects of the catecholamines were measured as a percentage inhibition of a standard acetylcholine (ACh)-induced contraction. Iso produced approximately 80% maximum inhibition of the standard ACh-contraction in all 4 stages of the oestrous cycle. Adr and NA produced 80% maximum inhibition in oestrus only, and 50-60% maximum inhibition in proestrus, metoestrus and dioestrus. The differences in the degree of inhibition produced by the catecholamines were overcome (i.e. the maximum inhibition produced by Adr and NA was increased to become equal to that produced by Iso) when experiments were repeated in the presence of the uptake inhibitors desmethylimipramine (DMI) and normetanephrine (NMN), but not in the presence of an alpha-adrenoceptor antagonist (azapetine 10(-7) M). Variations in the uptake of 3H-Iso and 3H-Na were observed in the different stages of the oestrous cycle. Small alpha-adrenoceptor mediated motor responses to NA and Adr were observed only in the presence beta-antagonist (propranolol 10(-5) M), in uteri from rats in oestrus, metoestrus and dioestrus, but not proestrus. It is concluded that in the rat isolated uterus, beta-inhibitory receptors predominate throughout the natural oestrous cycle, although the existence of alpha-excitatory receptors has been shown in 3 of the 4 stages.


Acute reperfusion therapy in acute myocardial infarction.
The ECG classification of acute myocardial infarctions has had a profound influence on the treatment of patients with AMI. Deciding whether a patient has ST-segment elevations or a new left bundle branch block or neither of these findings on ECG launches the treating physician down two different treatment pathways: patients with ST-elevation MI need to be assessed for immediate re-perfusion therapy, whereas patients with non-ST-elevation MI are best treated with aggressive medical management without acute reperfusion.


Canine fibroblast growth factor receptor 3 sequence is conserved across dogs of divergent skeletal size.
Fibroblast growth factor receptor 3 (FGFR3) is expressed in the growth plate of endochondral bones and serves as a negative regulator of linear bone elongation. Activating mutations severely limit bone growth, resulting in dwarfism, while inactivating mutations significantly enhance bone elongation and overall skeletal size. Domesticated dogs exhibit the greatest skeletal size diversity of any species and, given the regulatory role of FGFR3 on growth plate proliferation, we asked whether sequence differences in FGFR3 could account for some of the size differences. All exons, the promoter region, and 60 bp of the 3' flanking region of the canine FGFR3 gene were sequenced for nine different dog breeds representing a spectrum of skeletal size. The resultant sequences were compared to the reference Boxer genome sequence. There was no variation in sequence for any FGFR3 exons, promoter region, or 3' flanking sequence across all breeds evaluated. The results suggest that, regardless of domestication selection pressure to develop breeds having extreme differences in skeletal size, the FGFR3 gene is conserved. This implies a critical role for this gene in normal skeletal integrity and indicates that other genes account for size variability in dogs.


Acute renal failure in newborn infants.
The clinical course and follow-up of 14 neonates who developed acute renal failure are reported. Renal failure in these patients was secondary to major perinatal disorders, e.g., hyaline membrane disease, pneumonia, hemorrhage, or sepsis. Thirteen patients had hypoxia and nine were in shock when renal failure developed. Five patients died during the acute stage of renal failure. Of nine survivors, five patients sustained residual renal damage.


Oxidative stress response system in Escherichia coli arising from diphenyl ditelluride (PhTe)2 exposure.
The toxicity of diphenyl ditelluride (PhTe)2 is associated with its ability to oxidize sulfhydryl groups from biological molecules. Therefore, we evaluated possible molecular mechanisms of toxicity induced by this organochalcogen in Escherichia coli (E. coli) by evaluating oxidative damage markers, relative expression of genes associated with the cellular redox state in bacteria, such as katG, sodA, sodB, soxS, and oxyR, as well as the activity of enzymes responsible for cellular redox balance. After exposure of (PhTe)2 (6, 12, and 24 μg/mL), there was a decrease in non-protein thiols (NPSH) levels, an increase in protein carbonylation and lipid peroxidation in E. coli. Intra- and extracellular reactive species (RS) was increased at concentrations of 6, 12, and 24 μg/mL. The superoxide dismutase (SOD) activity was increased at the three concentrations tested, while catalase (CAT) activity was higher at 12 and 24 μg/mL. The soxS gene showed lower expression at the three concentrations tested, while the oxyR gene was supressed at 24 μg/mL. The katG antioxidant response gene showed lower expression, and sodA and sodB were positively activated, except for sodB at 6 μg/mL. Our findings demonstrate that exposure to (PhTe)2 induced RS formation, NPSH depletion and changes in transcriptional factors regulation, characterizing it as a multi-target compound, causing disruption in cellular oxidative state, as well as molecular mechanisms associated in E. coli.


Developmental changes in the in vitro activated regenerative activity of primitive mammary epithelial cells.
Many normal adult tissues contain rare stem cells with extensive self-maintaining regenerative potential. During development, the stem cells of the hematopoietic and neural systems undergo intrinsically specified changes in their self-renewal potential. In the mouse, mammary stem cells with transplantable regenerative activity are first detectable a few days before birth. They share some phenotypic properties with their adult counterparts but are enriched in a subpopulation that displays a distinct gene expression profile. Here we show that fetal mammary epithelial cells have a greater direct and inducible growth potential than their adult counterparts. The latter feature is revealed in a novel culture system that enables large numbers of in vitro clonogenic progenitors as well as mammary stem cells with serially transplantable activity to be produced within 7 days from single fetal or adult input cells. We further show that these responses are highly dependent on novel factors produced by fibroblasts. These findings provide new avenues for elucidating mechanisms that regulate normal mammary epithelial stem cell properties at the single-cell level, how these change during development, and how their perturbation may contribute to transformation.


Study of MicroRNA Cluster Located on Chromosome X in Serum and Breast Cancer Tissue.
Breast cancer is a prevalent cancer type among women worldwide, with the second highest incidence rate. The objective of this study was to identify a non-invasive biomarker for detecting breast cancer, and to this end, miRNA clusters were investigated as potential candidates. A micro-RNA cluster located on the X chromosome q27.3 region was selected for the study. The research was conducted as a case-control study with a sample size of 100 patients with breast cancer and 100 healthy individuals. Tissue samples from breast cancer tumors and tumor margins were collected from the breast cancer patients. Following RNA extraction and RT-PCR, the expression of miRNA clusters, including miR-506, miR-507, miR-508, miR-509, miR-513, miR-888, miR-891, miR-892-a, and miR-892-b, was analyzed in the serum and breast tissue of the breast cancer patients. The expression of various micro-RNAs in the case and control serums was compared, and it was found that all mentioned micro-RNAs, except mir888-5p and mir-509-3p, exhibited significant and meaningful differences between the patients and control serum groups. These micro-RNAs can be considered as potential tumor markers with a confidence level of P-value = 0.0001. In contrast, mir888-5p and mir-509-3p were considered non-significant. The expression of all micro-RNAs in the tumor margin and BC tumor was significant with a P-value < 0.0001. Based on the ROC curves, all the mentioned microRNAs, except mir-888-5p, mir-513-a-5p, and mir-509-3p, exhibited high sensitivity and specificity and can be considered remarkable non-invasive tumor markers for breast cancer detection.


Role of the proposed pore-forming segment of the Ca2+ release channel (ryanodine receptor) in ryanodine interaction.
In earlier studies we showed that point mutations introduced into the proposed pore-forming segment, GVRAGGGIGD (amino acids 4820-4829), of the mouse cardiac ryanodine receptor reduced or abolished high affinity [3H]ryanodine binding. Here we investigate the effects of these mutations on the affinity and dissociation properties of [3H]ryanodine binding and on ryanodine modification of the ryanodine receptor channel at the single channel and whole cell levels. Scatchard analysis and dissociation studies reveal that mutation G4824A decreases the equilibrium dissociation constant (K(d)) and the dissociation rate constant (k(off)), whereas mutations G4828A and D4829A increase the K(d) and k(off) values. The effect of ryanodine on single G4828A and D4829A mutant channels is reversible on the time scale of single channel experiments, in contrast to the irreversible effect of ryanodine on single wild-type channels. Ryanodine alone is able to induce a large and sustained Ca2+ release in HEK293 cells transfected with the R4822A or G4825A mutant cDNA at the resting cytoplasmic Ca2+ but causes little or no Ca2+ release in cells transfected with the wild-type cDNA. Mutation G4826C diminishes the functional effect of ryanodine on Ca2+ release but spares caffeine-induced Ca2+ release in HEK293 cells. Co-expression of the wild-type and G4826C mutant proteins produces single channels that interact with ryanodine reversibly and display altered conductance and ryanodine response. These results are consistent with the view that the proposed pore-forming segment is a critical determinant of ryanodine interaction. A putative model of ryanodine-ryanodine receptor interaction is proposed.


Overexpression of iASPP-SV in glioma is associated with poor prognosis by promoting cell viability and antagonizing apoptosis.
Inhibitor of apoptosis-stimulating protein of p53 (iASPP), encoded by PPP1R13L gene, is often overexpressed in human cancers. From the PPP1R13L gene, at least two isoforms, iASPP-L and iASPP-SV, are produced through alternative splicing. However, the role of these isoforms in glioma is still elusive. In this study, we examined the expression of iASPP-SV in astrocytic glioma tissues with different grades and normal human cerebral tissues. The result showed a higher messenger RNA (mRNA) expression level of iASPP-SV in astrocytic glioma patients with World Health Organization (WHO) grade II to IV in comparison to the normal controls. Additionally, mRNA expression level of iASPP-SV was gradually increased with the raise of the grade in glioma. High mRNA expression level of iASPP-SV was significantly associated with malignant WHO grades (P < 0.001). The protein expression level of iASPP-SV was consistent with the mRNA expression level. The Kaplan-Meier analysis revealed that high iASPP-SV mRNA expression significantly affected overall survival and progression-free survival (both P < 0.001). Furthermore, multivariate analysis indicated that the mRNA expression of iASPP-SV was an independent prognostic marker in glioma (P < 0.001). To further explore the role of iASPP-SV in glioma, U87 cells were transfected with iASPP-SV by lentivirus and then treated with temozolomide (TMZ). Overexpression of iASPP-SV promoted the cell viability and downregulated the expression of pro-apoptosis genes (Bax, Puma, p21, and Noxa) to inhibit apoptosis induced by TMZ. Our study provides the first evidence that high iASPP-SV expression may be a novel prognostic factor and therapeutic target for glioma.


[Juvenile Gougerot Sjögren syndrome: report of 3 cases].
Gougerot Sjögren syndrome is rare during childhood. Diagnosis in adult patients is usually based on sets of criteria combining clinical, serological, and salivary gland histopathological findings. In the pediatric age group, clinical manifestations might be different from the adult form. We report on 3 cases of childhood Gougerot Sjögren syndrome.


Simultaneous immobilization of Pb, Cd and As in soil by hybrid iron-, sulfate- and phosphate-based bio-nanocomposite: Effectiveness, long-term stability and bioavailablity/bioaccessibility evaluation.
Here, the bio-nanocomposite (n-HFP + n-HFS)@An was developed to simultaneously immobilize Pb, Cd and As in the severely contaminated soil. The immobilization rates of diethylenetriaminepentaacetic acid (DTPA)/decarbonate-extracted bioavailable Pb, Cd and As were 59.87%, 31.28% and 62.30%, and the immobilization rates of their water-soluble forms were 63.12%, 60.02% and 89.39%, respectively. Moreover, the ten-year acid rain simulated leaching assay showed that the maximum cumulative release contents of Pb, Cd and As in the treated soil samples were decreased by 2.94, 2.46 and 40.60 times, comparing to the un-treated ones. Additionally, the results of SBRC (Solubility Bioaccessibility Research Consortium) revealed that the bioaccessible rates of the three metals in intestinal phase were lower than in gastric phase, and both of them decreased with increasing the immobilization time. The gastric bioaccessibility of Pb, Cd and As had a higher correlation with the contents of water-soluble forms, while the intestinal bioaccessibility was more strongly positively associated with the bioavailable forms.


The primary structure of a halorhodopsin from Natronobacterium pharaonis. Structural, functional and evolutionary implications for bacterial rhodopsins and halorhodopsins.
We cloned and sequenced the gene coding for the polypeptide of a halorhodopsin in Natronobacterium pharaonis (named here pharaonis halorhodopsin). Peptide sequencing of cyanogen bromide fragments, and immunoreactions of the protein and synthetic peptides derived from the COOH-terminal gene sequence, confirmed that the open reading frame is the structural gene for the pharaonis halorhodopsin polypeptide. The flanking DNA sequences, as well as those for other bacterial rhodopsins, were compared to previously proposed archaebacterial consensus sequences. In pairwise comparisons of the open reading frame with DNA sequences for bacterio-opsin and halo-opsin from Halobacterium halobium, silent divergences (mutations/nucleotide at codon positions which do not result in amino acid changes) were calculated. These indicate very considerable evolutionary distance between each pair of genes. In spite of this, the three protein sequences show extensive similarities, indicating strong selective pressures. Conserved and conservatively replaced amino acid residues in all three proteins identify general features essential for ion-motive bacterial rhodopsins, responsible for overall structure and chromophore properties. Comparison of the bacteriorhodopsin sequence with those of the two halorhodopsins, on the other hand, identifies features involved in their specific (proton and chloride ion) transport functions.


Enantioselective synthesis of a highly potent selective serotonin reuptake inhibitor. An application of imidazolidinone catalysis to the alkylation of indoles with an alpha,beta-disubstituted alpha,beta-unsaturated aldehyde.
The synthesis of the highly potent and selective serotonin reuptake inhibitor 1 (BMS-594726) is described. In the key construction step, an enantioselective alkylation of the indole nucleus with an alpha-branched alpha,beta-unsaturated aldehyde 7 was accomplished utilizing MacMillan's imidazolidinone catalyst 3b. A rationale is presented for the unexpected stereochemical result, as well as the novel reactivity of the alpha-branched substrate. [reaction: see text]


Risk Perception and Knowledge, Attitudes, and Practices Against COVID-19 in a Hypertensive Population From a Semi-Urban City of Ecuador.
Background: In an elderly population with hypertension, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a higher incidence of mortality and a protracted course of clinical symptoms. Objective: To assess the perceived risk of infection and complications due to COVID-19 in people with hypertension living in a semi-urban city of Ecuador. Methods: A cross-sectional telephone survey of adult outpatients with a previous diagnosis of hypertension in the semi-urban community of Conocoto in Quito, Ecuador was conducted from August to December 2020. Results: A total of 260 adult outpatients, aged 34-97 years, completed telephone surveys. Of total, 71.5% (n = 186) of respondents were women and 28.5% (n = 74) of respondents were men. Overall, 18.1% believe that their risk of infection is "very high," 55.4% believe that their risk of infection is "high," 21.5% believe that their risk of infection is "low," and 5% believe that their risk of infection is "very low." The perceived risk of complications, if infected by COVID-19, revealed that 21.9% believe that their risk of complication is "very high," 65.0% believe that their risk of complication is "high," 10.4% believe that their risk of complication is "low," and 2.7% believe that their risk of complication is "very low." Conclusion: Patients with hypertension are aware of the risks posed by COVID-19 infection and its impact on their health. However, the health system must educate the population on health practices and behaviors to avoid COVID-19 infection until the majority of the population of Ecuador can be vaccinated.


IRQN Award article: Radiology audit: a program developed for remote or solo-practicing radiologists: a New Zealand quality initiative.
New Zealand radiologists working in solo or locum tenens practice away from colleagues in hospital departments or at large practices may have problems satisfying peer review and audit requirements for the Medical Council of New Zealand and Royal Australian and New Zealand College of Radiologists. This paper describes a practical audit program developed by a small group of New Zealand radiologists that commenced in 2005. Each year, a set of cases with known clinical and pathologic outcomes is sent from one radiologist to the next on a rota system. Reports are e-mailed back, then audited, with comments being returned again by e-mail. Each radiologist therefore acts as both reporter and auditor, ensuring a spectrum of audit around the group. The cases are reported blind, but usually, a limited amount of clinical information is provided, as would be the case on a request form in clinical practice. The process of audit is described, and the reaction to and acceptance of the program by the participants have been surveyed at the end of the first year of operation. The program has achieved overall acceptance by the group and is approved by the continuing medical education committee of the college, hence satisfying the Medical Council of New Zealand.


Incorporating health equity in the neurology curriculum: Our experience.
Social determinants of health (SDoH) are responsible for 80-90% of modifiable contributors to health, yet this material may not be covered in preclinical medical school neuroscience courses. To describe how topics related to SDoH and inclusion, diversity, equity, anti-racism, and social justice (IDEAS) were incorporated into a preclinical neuroscience course. IDEAS concepts and guided discussions were added to our existing case-based curriculum, and guest speakers were invited to discuss how these concepts are relevant in the field of neurology. Most students felt that content and discussions were integrated thoughtfully. Students also found it helpful to learn and observe how faculty address these topics in real-world cases. The additional content related to SDoH and IDEAS is feasible. Faculty with or without expertise in IDEAS concepts were able to utilize these cases and generate discussion without detracting from the neuroscience course material.


Accessibility of Enzymatically Delignified Bambusa bambos for Efficient Hydrolysis at Minimum Cellulase Loading: An Optimization Study.
In the present investigation, Bambusa bambos was used for optimization of enzymatic pretreatment and saccharification. Maximum enzymatic delignification achieved was 84%, after 8 h of incubation time. Highest reducing sugar yield from enzyme-pretreated Bambusa bambos was 818.01 mg/g dry substrate after 8 h of incubation time at a low cellulase loading (endoglucanase, β-glucosidase, exoglucanase, and xylanase were 1.63 IU/mL, 1.28 IU/mL, 0.08 IU/mL, and 47.93 IU/mL, respectively). Enzyme-treated substrate of Bambusa bambos was characterized by analytical techniques such as Fourier transformed infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM). The FTIR spectrum showed that the absorption peaks of several functional groups were decreased after enzymatic pretreatment. XRD analysis indicated that cellulose crystallinity of enzyme-treated samples was increased due to the removal of amorphous lignin and hemicelluloses. SEM image showed that surface structure of Bambusa bambos was distorted after enzymatic pretreatment.


New insights into the effects and mechanism of a classic traditional Chinese medicinal formula on influenza prevention.
KangBingDu (KBD) is a classic traditional Chinese medicinal formula widely used to treat influenza. However, little information is available from controlled studies regarding the anti-influenza pharmacological activities of KBD and its underlying mechanisms, at least partly due to the lack of appropriate study models. We hypothesized that KBD might provide a protection against influenza infection by reducing the host's susceptibility to viruses. To prove it, mouse restraint stress model was employed. Mice were restricted and infected with influenza virus. KBD (13 and 26mg/kg/d) was orally administrated to mice from the first day of restraint stress and lasted for 7 days (twice a day). Mice were monitored daily for morbidity, symptom severity, and mortality for 21 days. The histopathologic changes were examined. For the study of mechanisms of action, we investigated whether KBD could promote mitochondria antiviral signaling protein (MAVS)-mediated antiviral signal and inhibit nuclear factor-kappa B (NF-κB)-mediated inflammation response. KBD significantly decreased the susceptibility of restraint mice to influenza virus, as evidenced by lowered mortality, attenuated inflammation and reduced viral replications in lungs. Further results revealed that KBD elevated the protein expression of MAVS, which subsequently increased the IFN-β and IFITM3 protein levels, thereby helping to fight viral infections. Finally, we identified that (R,S)-goitrin, mangiferin, forsythin and forsythoside A were effective components in KBD against influenza viral infections. KBD can reduce the susceptibility to influenza virus via mitochondrial antiviral signaling.


Electrical responses of the marine ciliate Euplotes vannus (hypotrichia) to mechanical stimulation at the posterior cell end.
Electrical responses upon mechanostimulation at the posterior cell end were investigated in the marine hypotrichous ciliate Euplotes vannus. A new mechanostimulator was developed to mimic stimuli that are identical with those involved in cell-cell collisions. The receptor potential hyperpolarized by 18-35 mV within 12-25 msec, reached a peak value of -62 mV with a delay of 4-9 msec after membrane deformation, and was deactivated after 50-70 msec. Cirri were stimulated to beat accelerated backward. The corresponding receptor current exerted a similar time course with a peak of 2.4 nA. The shift of the reversal potential by 57.6 mV at a tenfold increase of [K+]o identifies potassium ions as current carriers within the development of the receptor potential. An intracellular K concentration of 355 mmol/liter was calculated for cells in a medium that was composed similar to sea-water. The mechanically activated potassium current was totally inhibited by extracellular TEA and intracellular Cs+, and partially inhibited by extracellular 4-AP. The total inhibition of the current by injected EGTA points to a Ca dependence of the posterior mechanosensitivity. It was confirmed by the increase of the peak current amplitude with rising [Ca2+]o. Sodium presumably repolarizes the receptor potential because the repolarization was delayed and after-depolarizations were eliminated in media without sodium. Since deciliation did not affect mechanosensitivity, the corresponding ion channels reside within the soma membrane.


Disinfection in bed-pan washers.
The degree of bacterial contamination on naturally soiled bed-pans, wash-bowls and urinals in an orthopaedic surgery ward has been studied before and after treatment in automated bed-pan washers with the water temperature in the final rinse above 85 degrees C and below 70 degrees C. In the machines studied, the degree of remaining contamination after treatment with a low-temperature final rinse was considered to be unacceptably high, probably due to an insufficient cleaning effect. In spite of this insufficient cleaning effect, after treatment with the water temperature in the final rinse above 85 degrees C the remaining bacterial contamination was less than one colony-forming unit per square centimetre in bed-pans and wash-bowls and less than 50 microorganisms per urinal. This is considered to be far below an acceptable upper limit.


Silicosis due to intentional inhalation of abrasive scouring powder. Case report with long-term survival and vasculitic sequelae.
Silicosis due to inhalation of abrasive scouring powder is now an unusual event. We report a nonindustrial case of acute silicosis due to intentional inhalation of commercial, silica-containing scouring powder. This case is unique in that the patient had a 20 year survival (after onset of symptoms) with typical roentgenographic and histopathologic changes of silicosis, and evidence of immune complex disease in extrapulmonary tissues.


Enzymatic colorimetric method for turn-on determination of l-lactic acid through indicator displacement assay.
l-Lactic acid is a natural α-hydroxy carboxylic acid and is commonly used as an addictive. Quantitation of l-lactic acid is indispensable in food and cosmetic industries. An enzymatic colorimetric method was developed for the determination of l-lactic acid by competitive indicator displacement assay. Boric acid inhibited the colorimetric reaction of l-3,4-dihydroxyphenylalanine (l-DOPA) catalyzed by tyrosinase. l-Lactic acid competitively displaced and released l-DOPA bound with boric acid to serve as substrate, and thus restored the tyrosinase activity. Recovery of color reaction could be spectrophotometrically determined at 475 nm and was proportional to the amount of l-lactic acid. A calibration curve between l-lactic acid concentration and recovery of absorbance were built. The concentration range of the l-lactic acid was 0.25-2.25 mM. The limit of detection (LOD) and the limit of quantification (LOQ) for l-lactic acid was estimated to be 0.05 mM and 0.16 mM, respectively. The method achieved turn-on and visual sensing with good precision, accuracy, specificity, and robustness. The assay method exhibited a promising prospect to determine the content of l-lactic acid in foods and cosmetics.


Environmental, human health and socioeconomic impacts of Ostreopsis spp. Blooms in the NW Mediterranean.
This paper summarizes the research conducted by the partners of the EU co-funded CoCliME project to ascertain the ecological, human health and economic impacts of Ostreopsis (mainly O. cf. ovata) blooms in the NW Mediterranean coasts of France, Monaco and Spain. This knowledge is necessary to design strategies to prevent, mitigate and, if necessary, adapt to the impacts of these events in the future and in other regions. Ostreopsis proliferations in the Mediterranean have been related to massive mortalities of benthic organisms and to symptoms of respiratory and cutaneous irritation in humans. A six-year epidemiologic study in a Ostreopsis hot spot in Catalonia and the accumulated experience of the French Mediterranean National Ostreopsis Surveillance Network confirm the main effects of these blooms on human health in the NW Mediterranean. The impacts are associated to direct exposure to seawater with high Ostreopsis cell concentrations and to inhalation of aerosols containing unknown irritative chemicals produced under certain circumstances during the blooms. A series of mild acute symptoms, affecting the entire body as well as the ophthalmic, digestive, respiratory and dermatologic systems have been identified. A main remaining challenge is to ascertain the effects of the chronic exposure to toxic Ostreopsis blooms. Still, the mechanisms involved in the deletereous effects of Ostreopsis blooms are poorly understood. Characterizing the chemical nature of the harmful compounds synthesized by Ostreopsis as well as the role of the mucus by which cells attach to benthic surfaces, requires new technical approaches (e.g., metabolomics) and realistic and standardized ecotoxicology tests. It is also necessary to investigate how palytoxin analogues produced by O. cf. ovata could be transferred through the marine food webs, and to evaluate the real risk of seafood poisonings in the area. On the other hand, the implementation of beach monitoring and surveillance systems in the summer constitutes an effective strategy to prevent the impacts of Ostreopsis on human health. In spite of the confirmed noxious effects, a survey of tourists and residents in Nice and Monaco to ascertain the socioeconomic costs of Ostreopsis blooms indicated that the occurrence of these events and their impacts are poorly known by the general public. In relationship with a plausible near future increase of Ostreopsis blooms in the NW Mediterranean coast, this survey showed that a substantial part of the population might continue to go to the beaches during Ostreopsis proliferations and thus could be exposed to health risks. In contrast, some people would not visit the affected areas, with the potential subsequent negative impacts on coastal recreational and touristic activities. However, at this stage, it is too early to accurately assess all the economic impacts that a potentially increasing frequency and biogeographic expansion of the events might cause in the future.


Inhibition of phospholipaseD2 increases hypoxia-induced human colon cancer cell apoptosis through inactivating of the PI3K/AKT signaling pathway.
Hypoxia is a common feature of solid tumor, and is a direct stress that triggers apoptosis in many human cell types. As one of solid cancer, hypoxia exists in the whole course of colon cancer occurrence and progression. Our previous studies shown that hypoxia induce high expression of phospholipase D2 (PLD2) and survivin in colon cancer cells. However, the correlation between PLD2 and survivin in hypoxic colon cancer cells remains unknown. In this study, we observed significantly elevated PLD2 and survivin expression levels in colon cancer tissues and cells. This is a positive correlation between of them, and co-expression of PLD2 and survivin has a positive correlation with the clinicpatholic features including tumor size, TNM stage, and lymph node metastasis. We also found that hypoxia induced the activity of PLD increased significant mainly caused by PLD2 in colon cancer cells. However, inhibition the activity of PLD2 induced by hypoxia promotes the apoptosis of human colon cancer cells, as well as decreased the expression of apoptosis markers including survivin and bcl2. Moreover, the pharmacological inhibition of PI3K/AKT supported the hypothesis that promotes the apoptosis of hypoxic colon cancer cells by PLD2 activity inhibition may through inactivation of the PI3K/AKT signaling pathway. Furthermore, interference the PLD2 gene expression leaded to the apoptosis of hypoxic colon cancer cells increased and also decreased the expression level of survivin and bcl2 may through inactivation of PI3K/AKT signaling pathway. These results indicated that PLD2 play antiapoptotic role in colon cancer under hypoxic conditions, inhibition of the activity, or interference of PLD2 gene expression will benefit for the treatment of colon cancer patients.


The bile acids binding of the fibre-rich fractions of three starchy legumes.
The bile acid binding to undigestible fibre has a significance on bile acids excretion. This was known to result in lowering blood cholesterol (for the use of cholesterol in bile acid formation) as well as reducing the colorectal cancer risk (through decreased formation of secondary bile acids). Compared to the model fibres Solka floc and carboxymethylcellulose (CMC), the investigated fibre fractions of lentils, broad beans and butter beans, were found to bind more cholic acid and chenodeoxycholic acid under conditions simulating the small intestine.


Acute allergic reaction after composite pollen ingestion.
Three patients are presented who ingested a health food known as "bee pollen" and who experienced an immediate allergic reaction. Examination revealed that the bee pollen contained dandelion pollen, which belongs to the Compositae family as does ragweed. In vivo and in vitro studies demonstrated that the patients were sensitive to several Compositae family members, rather than to insect-derived antigens. In addition, radioallergosorbent inhibition studies confirmed the suspected cross-reactivity between the health food and Compositae pollens. This study indicates that atopic individuals may experience anaphylaxis from ingestion of antigens in certain food stuffs that cross-react with pollens to which they are sensitive.


A comparison of serum and EDTA plasma in the measurement of glutamic acid decarboxylase autoantibodies (GADA) and autoantibodies to islet antigen-2 (IA-2A) using the RSR radioimmunoassay (RIA) and enzyme linked immunosorbent assay (ELISA) kits.
Glutamic acid decarboxylase antibodies (GADA) and tyrosine phosphatase antibodies (islet antigen-2 antibodies; IA-2A) are used in clinical practise to identify type 1 diabetes. GADA and IA-2A were measured with RSR-ELISA kits in samples from 76 newly diagnosed type 1 diabetic children and 120 healthy controls. The aim was to evaluate performance of RSR-ELISA kits for GADA and IA-2A when serum and Ca2+ treated plasma were used. GADA achieved high area under the curve (AUC) both for serum 0.95 (95% CI 0.90-0.99) and for Ca2+ treated plasma 0.95 (95% CI 0.91-0.99). At specificity 98%, sensitivity was 84% for serum and 87% for Ca2+ treated plasma. IA-2A achieved AUC 0.92 (95% CI 0.87-0.97) for serum and 0.94 (95% CI 0.90-0.98) for Ca2+ treated plasma. Using the lowest standard (15 WHO-Units/ml) as cut-off, specificity for serum was 100% and for Ca2+ treated plasma 99% with sensitivity 74% in both cases. Sensitivity was higher in ELISA compared to RIA (74%; p = 0.0080) for GADA measurement and similar for ELISA and RIA IA-2A measurements (76%; p = 0.50). Both RSR-ELISAs, GADA and IA-2A showed excellent performance for serum as well as for Ca2+ treated plasma.


Immunoglobulin G4-related disease in the sigmoid colon in patient with severe colonic fibrosis and obstruction: A case report.
Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated condition characterized by abundant IgG4 positive plasma cells and fibrosis in the affected tissues. It affects most parts of the body; however, there are not many reports on IgG4-RD involving the colon. A 50-year-old man complaining of intermittent fever for more than two years was referred to our hospital. Based on various investigations before surgery, we diagnosed him with chronic perforation of the sigmoid colon caused by inflammatory change or tumor. IgG blood tests before the operation suggested IgG4-RD, and postoperative pathology confirmed this prediction. We present a patient with IgG4-RD with colon involvement, which is an uncommon site. This report will expand the understanding of IgG4-RD in unknown tissues.


A Randomized Intervention to Assess the Effectiveness of an Educational Video on Organ Donation Intent.
The primary objective of this study was to evaluate the effectiveness of an emotive educational video on organ donation intent in New York City. The secondary study objective was to determine if the educational video affected various factors associated with organ donation. New York City residents were recruited via a crowdsourcing online platform and randomized to one of two groups, with exposure to viewing (1) an educational video before completing an 81 question survey on organ donation ("video first" condition) or (2) after completing the survey ("video last" condition). Logistic regression analysis compared organ donation intent (i.e., "how likely are you to become an organ donor") between the two groups. Additional variables related to organ donation (e.g., religious beliefs, financial incentives) were also evaluated between the two groups. Analyses were adjusted for organ donation registration status. In total, 1905 participants were randomized. We observed a statistically significant increased odds of organ donation intent among those randomized to the video first condition compared with those randomized to the video last condition (odds ratio [OR], 1.70; 95% confidence interval [95% CI], 1.29 to 2.24). Differences regarding both educational effect on nondonors and racial differences such that there was a decreased odds of organ donation intent among those who identified as Black compared with those who were White (OR, 0.66; 95% CI, 0.47 to 0.92). Black participants were also more likely to report bodily integrity and differential treatment by doctors compared with White participants. Our findings suggest that future interventions to increase organ donation registration among ethnically diverse populations could be effective if sufficient information is presented before decision making to addresses potential concerns.


Venous flow dynamics during spinal block in normotensive and hypertensive elderly patients: a duplex ultrasonographic study.
Spinal block induces hyperkinetic change in lower extremity blood flow. We compared the venous flow dynamic responses to spinal block in normotensive and hypertensive elderly patients. Following spinal block using 10 mg 0.5% (w/v) bupivacaine, we measured changes in blood pressure, heart rate, and venous flow dynamics of the popliteal vein by duplex ultrasonography in 20 normotensive (NBP group) and 18 hypertensive (HIBP group) patients. Spinal block caused significant decreases in blood pressure in both groups; similar rates of hypotension were observed. At baseline, peak velocity, time-averaged maximum velocity, and time-averaged mean velocity were higher in the HIBP than in the NBP group. During spinal block, peak velocity increased in both groups, and the between-group differences were no longer significant. At baseline, volume flow in the two groups was similar and increased by 141.5% in the NBP and 131.7% in the HIBP group during spinal block. Blood pressure and flow dynamics in the popliteal vein showed similar changes during spinal anaesthesia in elderly patients taking antihypertensive medication and normotensive patients, despite differences in baseline values.


[Breech Presentation: CNGOF Guidelines for Clinical Practice - Information and Management].
To provide guidelines regarding parents' information in case of breech presentation and labour ward organisation for trial of labour in breech presentation. Medline and Cochrane Library databases search and review of the main foreign guidelines. Information should be in favour of external cephalic version and describe benefits and risks for planned vaginal delivery vs planned caesarean delivery (Professional consensus). Patient should be aware of choice change according to obstetrical context (Professional consensus). Presence of an obstetrician is required at birth as well as immediate assistance of an anaesthesiologist and paediatrician if needed (Professional consensus). Information should lead to concerted choice concerning mode of delivery. Labour ward organisation requires presence of an obstetrician at birth and immediate availability of anaesthesiologist and paediatrician.


Antimutagens from Momordica charantia.
The antimutagenic principle of the green fruits of Momordica charantia was shown by the micronucleus test to be an intractable mixture of novel acylglucosylsterols. The antimutagens were extracted from the green fruits with ethanol and isolated from the bioactive petroleum ether and carbon tetrachloride extracts by repeated and sequential flash column chromatography. The major component of the mixture is 3-O-[6'-O-palmitoyl-beta-D-glucosyl-stigmasta-5,25(27)-dien and the minor component is the stearyl derivative (Guevara, 1989). At a dosage range in mice of 50-12.5 micrograms extract/g, the mixture reduced by about 80% the number of micronucleated polychromatic erythrocytes induced by the well-known mutagen mitomycin C. Structure-activity correlation studies suggested that the antimutagenic activity may reside in the peculiar lipid-like structure of the acylglucosylsterols. Ingestion of these compounds may result in their absorption in the plasma membrane lipid bilayer which could adversely affect the membrane permeability towards mitomycin C and disrupt the cellular activity of the latter.


Cholecystokinin-octapeptide antagonizes morphine analgesia in periaqueductal gray of the rat.
The analgesic effect of systemic morphine (5 mg/kg, s.c.) was dose-dependently antagonized by CCK-8 administered to the periaqueductal gray (PAG) of the rat. This effect could be reversed by proglumide, a CCK-receptor antagonist. The effect of morphine analgesia was potentiated by proglumide administered to PAG. These results are compatible with the notion that PAG is a strategic site where CCK-8 exerts an antiopioid activity.


Calcitriol concomitantly enhances insulin sensitivity and alters myocellular lipid partitioning in high fat-treated skeletal muscle cells.
Vitamin D reduces myocellular insulin resistance, but the effects of vitamin D on intramyocellular lipid (IMCL) partitioning are unknown. The purpose of this study was to understand how calcitriol, the active vitamin D metabolite, affects insulin sensitivity and lipid partitioning in skeletal muscle cells. C2C12 myotubes were treated with calcitriol (100 nM) or vehicle control for 96 h. Insulin-stimulated Akt phosphorylation (Thr 308) was determined by western blot. Intramyocellular triacylglycerol (IMTG), diacylglycerol (DAG), and ceramide content were measured by LC/MS. IMTG partitioning and lipid droplet accumulation were assessed by oil red O. Expression of genes involved in lipid droplet packaging and lipolysis were measured by RT-PCR. Compared to vehicle-treated myotubes, calcitriol augmented insulin-stimulated pAkt. Calcitriol increased total ceramides and DAG in a subspecies-specific manner. Specifically, calcitriol preferentially increased ceramide 24:1 (1.78 fold) and di-18:0 DAG (46.89 fold). Calcitriol increased total IMTG area as assessed by oil red O, but decreased the proportion of lipid within myotubes. Calcitriol increased mRNA content of genes involved in lipid droplet packaging (perilipin 2; PLIN 2, 2.07 fold) and lipolysis (comparative gene identification-58; CGI-58 and adipose triglyceride lipase; ATGL, ~ 1.80 fold). Calcitriol alters myocellular lipid partitioning and lipid droplet packaging which may favor lipid turnover and partially explain improvements in insulin sensitivity.


Up-regulated SAMD9L modulated by TLR2 and HIF-1α as a promising biomarker in tuberculosis.
The aim of this study was to identify potential biomarkers of TB in blood and determine their function in Mtb-infected macrophages. First of all, WGCNA was used to analyse 9451 genes with significant changes in TB patients' whole blood. The 220 interferon-γ-related genes were identified, and then 30 key genes were screened using Cytoscape. Then, the AUC values of key genes were calculated to further narrow the gene range. Finally, we identified 9 genes from GSE19444. ROC analysis showed that SAMD9L, among 9 genes, had a high diagnostic value (AUC = 0.925) and a differential diagnostic value (AUC>0.865). To further narrow down the range of DEGs, the top 10 hub-connecting genes were screened from monocytes (GSE19443). Finally, we obtained 4 genes (SAMD9L, GBP1, GBP5 and STAT1) by intersections of genes from monocytes and whole blood. Among them, it was found that the function of SAMD9L was unknown after data review, so this paper studied this gene. Our results showed that SAMD9L is up-regulated and suppresses cell necrosis, and might be regulated by TLR2 and HIF-1α during Mtb infection. In addition, miR-181b-5p is significantly up-regulated in the peripheral blood plasma of tuberculosis patients, which has a high diagnostic value (AUC = 0.969).


miR-134-5p Promotes Stage I Lung Adenocarcinoma Metastasis and Chemoresistance by Targeting DAB2.
Despite surgery and adjuvant therapy, early-stage lung adenocarcinoma (LUAD) treatment often fails due to local or metastatic recurrence. However, the mechanism is largely unknown. Here, we report that increased expression levels of miR-134-5p and decreased levels of disabled-2 (DAB2) were significantly correlated with recurrence in stage I LUAD patients. Our data show that miR-134-5p overexpression or DAB2 silencing strongly stimulated LUAD cell metastasis and chemoresistance. In contrast, inhibition of miR-134-5p or overexpression of DAB2 strongly suppressed LUAD cell metastasis and overcame the insensitivity of chemoresistant LUAD cells to chemotherapy. In addition, we demonstrated that DAB2 is a target of miR-134-5p and that miR-134-5p stimulates chemoresistance and metastasis through DAB2 in LUAD. Taken together, these findings suggest that miR-134-5p and its target gene DAB2 have potential as a biomarker for predicting recurrence in stage I LUAD patients. Additionally, miR-134-5p inhibition or DAB2 restoration may be a novel strategy for inhibiting LUAD metastasis and overcoming LUAD cell resistance to chemotherapy.


Levels, distributions and influential factors of residential airborne culturable bacteria in 12 Chinese cities: Multicenter on-site survey among dwellings.
Residential airborne culturable bacteria (RAB) are commonly used to assess indoor microbial loads, which is a very effective and recognized indicator of public concern about residential air quality. Many countries and organizations have set exposure limits for residential bacteria. Nevertheless, few studies have been conducted in multicenter cities about the distribution and influencing factors of RAB. It is a challenge to investigate the distribution of RAB and identify the association between indoor influencing variables and RAB in China. The current finding implied the comparative results from a one-year on-site survey of 12 cities in China. The concentration of RAB ranged from 0 CFU/m3 to 18,078 CFU/m3, with an arithmetic median of 350 CFU/m3. RAB concentrations were more in the warm season than those in the cold season, and were more in the bedrooms than those in the living rooms. Indoor environmental indicators (including PM2.5 and PM10) showed the mediating role in the process of temperature and relative humidity effects on RAB. . Influential factors including family-related information (income), architectural characteristics (house type, building history, living floor, the layers of window glass, and decoration) and lifestyle behaviors (heating, new furniture, incense-burned, insecticides-used, air condition-used, and plants-growed) were related with the concentration of RAB. This study presents essential data on the distribution of RAB in some Chinese cities, and reveals the residential influential factors that might minimize health risk from RAB.


A simple strategy to enhance the in vivo wound-healing activity of curcumin in the form of self-assembled nanoparticle complex of curcumin and oligochitosan.
While the wound healing activity of curcumin (CUR) has been well-established, its clinical effectiveness remains limited due to the inherently low aqueous CUR solubility, resulting in suboptimal CUR exposure in the wound sites. Previously, we developed high-payload amorphous nanoparticle complex (or nanoplex) of CUR and chitosan (CHI) capable of CUR solubility enhancement by drug-polyelectrolyte complexation. The CUR-CHI nanoplex, however, exhibited poor colloidal stability due to its strong agglomeration tendency. Herein we hypothesized that the colloidal stability could be improved by replacing CHI with its oligomers (OCHI) owed to the better charge distribution in OCHI. The effects of key parameters in drug-polyelectrolyte complexation (i.e. pH, salt inclusion, CUR concentration, and OCHI/CUR charge ratio) on the physical characteristics and preparation efficiency of the CUR-OCHI nanoplex produced were investigated. The in vivo wound healing efficacy of the CUR-OCHI nanoplex and its cytotoxicity towards human keratinocytes cells were examined. The results showed that CUR-OCHI nanoplex exhibited prolonged colloidal stability (72 h versus <24 h for the CUR-CHI nanoplex). At the optimal condition, the CUR-OCHI nanoplex (without ultrasonication) exhibited size, zeta potential, and CUR payload of ≈140 nm, 20 mV, and 78% (w/w), respectively. The nanoplex preparation was simple yet robust at nearly 100% CUR utilization rate. The CUR-OCHI nanoplex exhibited superior wound healing efficacy to the native CUR with wound closure of >90% after 7 days versus 9 days for the native CUR resulting in smaller scars, attributed to its generation of high CUR concentration in the wound sites.


Tracking the migration of the Indian continent using the carbonate clumped isotope technique on Phanerozoic soil carbonates.
Approximately 140 million years ago, the Indian plate separated from Gondwana and migrated by almost 90° latitude to its current location, forming the Himalayan-Tibetan system. Large discrepancies exist in the rate of migration of Indian plate during Phanerozoic. Here we describe a new approach to paleo-latitudinal reconstruction based on simultaneous determination of carbonate formation temperature and δ(18)O of soil carbonates, constrained by the abundances of (13)C-(18)O bonds in palaeosol carbonates. Assuming that the palaeosol carbonates have a strong relationship with the composition of the meteoric water, δ(18)O carbonate of palaeosol can constrain paleo-latitudinal position. Weighted mean annual rainfall δ(18)O water values measured at several stations across the southern latitudes are used to derive a polynomial equation: δ(18)Ow = -0.006 × (LAT)(2) - 0.294 × (LAT) - 5.29 which is used for latitudinal reconstruction. We use this approach to show the northward migration of the Indian plate from 46.8 ± 5.8°S during the Permian (269 M.y.) to 30 ± 11°S during the Triassic (248 M.y.), 14.7 ± 8.7°S during the early Cretaceous (135 M.y.), and 28 ± 8.8°S during the late Cretaceous (68 M.y.). Soil carbonate δ(18)O provides an alternative method for tracing the latitudinal position of Indian plate in the past and the estimates are consistent with the paleo-magnetic records which document the position of Indian plate prior to 135 ± 3 M.y.


Audiological and Speech Outcomes of Cochlear Implantation in Inner Ear Malformation Compared to the Normal Inner Ear.
To compare the overall clinical outcomes of cochlear implantation in children with structural inner ear abnormalities, with results of implantation in children with radiologically 'normal' inner ears. To study the incidence and performance outcomes of cochlear implantation in children with inner ear malformations (IEMs). It is a retrospective case control study of 57 normal and 57 abnormal inner ear patients operated for cochlear implant between Jan 1, 2014 and Aug 1, 2017, by Veria technique. The age range was between 12 months and 15 years. The prevalence of IEMs was 13.8%. Of the 57 cases with IEMs, 33.3% were of enlarged vestibular acqueduct, 7% were of isolated Incomplete Partition type-2, 21.1% cases were of Mondini's dysplasia, 3.5% of Incomplete partition type-1 and 8.8% of cochlear nerve hypoplasia. Most commonly encountered malformation was EVA while IP-1 was the least common malformation. A CSF gusher was experienced in 11 cases. There was a statistically significant difference between the CAP and SIR scores of both IEM and control groups, both at 1 year and at 2 years (1 year CAP score p value < 0.001, 2 year CAP score p value 0.002 and 1 year SIR score, p value < 0.001, 2 year SIR score, p value 0.013). There was progressive improvement in the scores (of both groups) at the 2 year mark, compared to 1 year scores. Cochlear implantation is safe and surgically feasible in children with IEMs. However, the hearing outcome and speech perception outcomes are poor than those of patients with normal anatomy, with an exception seen in enlarged vestibular aqueduct.


Epigenetic mechanisms of protein tyrosine phosphatase 6 suppression in diffuse large B-cell lymphoma: implications for epigenetic therapy.
Protein tyrosine phosphatases such as PTPN6 can be downregulated in various neoplasms. PTPN6 expression by immunohistochemistry in 40 diffuse large B-cell lymphoma (DLBCL) tumors was lost or suppressed in 53% (21/40). To elucidate the molecular mechanisms of PTPN6 suppression, we performed a comprehensive epigenetic analysis of PTPN6 promoter 2 (P2). None of the DLBCL primary tumors (0/37) had PTPN6 hypermethylation on the CpG1 island using methylation-specific PCR, pyrosequencing, and high-resolution melting assays. However, hypermethylation in 57% (21/37) of cases was found in a novel CpG island (CpG2) in P2. PTPN6 gene suppression was reversed by 5-aza-deoxycytidine (5-Aza), a DNA methyltransferase inhibitor, and the histone deacetylase inhibitor (HDACi) LBH589. LBH589 and 5-Aza in combination inhibited DLBCL survival and PTPN6 hypermethylation at CpG2. The role of histone modifications was investigated with a chromatin-immunoprecipitation assay demonstrating that PTPN6 P2 is associated with silencing histone marks H3K27me3 and H3K9me3 in DLBCL cells but not normal B cells. 3-Deazaneplanocin A, a histone methyltransferase inhibitor, decreased the H3K27me3 mark, whereas HDACi LBH589 increased the H3K9Ac mark within P2 resulting in re-expression of PTPN6. These studies have uncovered novel epigenetic mechanisms of PTPN6 suppression and suggest that PTPN6 may be a potential target of epigenetic therapy in DLBCL.


Bacteria and zymosan opsonized with histone, dextran sulfate, and polyanetholesulfonate trigger intense chemiluminescence in human blood leukocytes and platelets and in mouse macrophages: modulation by metabolic inhibitors in relation to leukocyte-bacteria interactions in inflammatory sites.
Human blood leukocytes and platelets and mouse peritoneal macrophages emit very rapid and very intense Luminol-dependent chemiluminescence (CL) signals when treated with streptococci, staphylococci, or with zymosan, which have been preopsonized with arginine-rich histone, dextran sulfate or polyanetholesulfonate (liquoid). Liquoid alone at 10-30 micrograms/2 X 10(5) leukocytes also triggers intense CL responses in the absence of a carrier. Strong CL can also be triggered, and at the same levels, when the various polyelectrolytes are simply mixed with the bacteria or zymosan and added to the leukocyte suspensions. The CL responses induced by the polyelectrolyte-bacteria complexes greatly exceed those triggered in leukocytes by antibody-complement-coated particles. Liquoid also shows a unique property of markedly augmenting CL signals which have already been induced by other ligand-coated bacteria or zymosan particles. Streptococci and staphylococci were found to be much superior to zymosan, Gram-positive bacilli, or E. coli as carriers for the various polyelectrolytes in the CL reaction. Neither protamine sulfate, lysozyme, myeloperoxidase, crystalline ribonuclease (all cationic in nature), chondroitin sulfate, heparin, nor alginate sulfate acted as ligands for triggering CL, when used to opsonize bacteria or zymosan. The induction of CL in blood leukocytes by the various ligand-coated bacteria is markedly inhibited by azide, KCN catalase, aminotriazole, and EDTA, agents known to inhibit the production of oxygen radicals following stimulation of leukocytes by opsonized bacteria. Two children diagnosed for chronic granulomatous diseases (CGD) of childhood and an apparently healthy sister of one of the male patients completely failed to respond with CL either to the polyelectrolyte-bacteria complexes, liquoid or antibody-coated bacteria and zymosan. It is proposed that liquoid be employed for the rapid screening of defects in certain oxygen-dependent metabolic processes in both PMNs and macrophages. It is also suggested that polyelectrolytes like the ones described in this study may markedly enhance the bactericidal properties of leukocytes and macrophages towards both extracellular and intracellular microorganisms and may perhaps also augment the tumoricidal effects of activated macrophages.


A model driven approach for the German health telematics architectural framework and security infrastructure.
Shared care concepts such as managed care and continuity of care are based on extended communication and cooperation between different health professionals or between them and the patient respectively. Health information systems and their components, which are very different in their structure, behavior, data and their semantics as well as regarding implementation details used in different environments for different purposes, have to provide intelligent interoperability. Therefore, flexibility, portability, and future orientation must be guaranteed using the newest development of model driven architecture. The ongoing work for the German health telematics platform based on an architectural framework and a security infrastructure is described in some detail. This concept of future proof health information networks with virtual electronic health records as core application starts with multifunctional electronic health cards. It fits into developments currently performed by many other developed countries.


Fungal Symbionts Produce Prostaglandin E2 to Promote Their Intestinal Colonization.
Candida albicans is a ubiquitous fungal symbiont that resides on diverse human barrier surfaces. Both mammalian and fungal cells can convert arachidonic acid into the lipid mediator, prostaglandin E2 (PGE2), but the physiological significance of fungus-derived PGE2 remains elusive. Here we report that a C. albicans mutant deficient in PGE2 production suffered a loss of competitive fitness in the murine gastrointestinal (GI) tract and that PGE2 supplementation mitigated this fitness defect. Impaired fungal PGE2 production affected neither the in vitro fitness of C. albicans nor hyphal morphogenesis and virulence in either systemic or mucosal infection models. Instead, fungal production of PGE2 was associated with enhanced fungal survival within phagocytes. Consequently, ablation of colonic phagocytes abrogated the intra-GI fitness boost conferred by fungal PGE2. These observations suggest that C. albicans has evolved the capacity to produce PGE2 from arachidonic acid, a host-derived precursor, to promote its own colonization of the host gut. Analogous mechanisms might undergird host-microbe interactions of other symbiont fungi.


Calcium-dependent up-regulation of mitochondrial electron transfer chain gene expressions in human luteinized granulosa cells.
To evaluate the transcription and translation ability of mitochondria in terminally differentiated granulosa cells, these cells were incubated with ionic calcium. Prospective laboratory research. In vitro fertilization laboratory in a university hospital. Granulosa cells were harvested from 50 female patients undergoing IVF. Analysis of mitochondrial gene expression by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and of mitochondrial-encoded proteins by Western blot. Comparison of the RNA expression levels of genes including cytochrome c oxidase subunit I (COX I), adenosine triphosphate synthase 6 (ATPase 6), flavoprotein, and succinate-ubiquinone oxidoreductase, and protein levels of COX I and flavoprotein in different calcium ion treatment groups. There were dose-dependent increases in RNA expressions of the four genes analyzed from granulosa cells cultured in a serial concentration of calcium ions. This effect was abolished when cells were preincubated with the extracellular calcium-chelating agent, Ethylene glycol-bis (2-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA). The effect of ionic calcium on both the nuclear- and mitochondrial-encoded subunits also was determined. Expression levels of mitochondrial transcription factor A in RNA significantly increased in granulosa cells that were exposed for 24 and 48 hours to 0.5 and 1 microM A23187. The present study is the first report to present calcium-dependent increases in the transcription and translation levels of both nuclear-encoded and mitochondrial-encoded mitochondrial respiratory enzyme subunits and also indicates that mitochondrial transcription factor A is involved in mitochondrial biogenesis.


Comparison of activity indexes for recognizing enzyme mutants of higher activity with uricase as model.
For screening a library of enzyme mutants, an efficient and cost-effective method for reliable assay of enzyme activity and a decision method for safe recognition of mutants of higher activity are needed. The comparison of activity concentrations of mutants in lysates of transformed Escherichia coli cells against a threshold is unsafe to recognize mutants of higher activity due to variations of both expression levels of mutant proteins and lysis efficiency of transformed cells. Hence, by a spectrophotometric method after verification to measure uricase activity, specific activity calculated from the level of total proteins in a lysate was tested for recognizing a mutant of higher activity. During uricase reaction, the intermediate 5-hydroxyisourate interferes with the assay of uric acid absorbance, but the measurement of absorbance at 293 nm in alkaline borate buffer was reliable for measuring uricase initial rates within a reasonable range. The level of total proteins in a lysate was determined by the Bradford assay. Polyacrylamide gel electrophoresis analysis supported different relative abundance of uricase mutant proteins in their lysates; activity concentrations of uricase in such lysates positively correlated with levels of total proteins. Receiver-operation-curve analysis of activity concentration or specific activity yielded area-under-the-curve close to 1.00 for recognizing a mutant with > 200% improvement of activity. For a mutant with just about 80% improvement of activity, receiver-operation-curve analysis of specific activity gave area-under-the-curve close to 1.00 while the analysis of activity concentration gave smaller area-under-the-curve. With the mean plus 1.4-fold of the standard deviation of specific activity of a starting material as the threshold, uricase mutants whose activities were improved by more than 80% were recognized with higher sensitivity and specificity. Specific activity calculated from the level of total proteins is a favorable index for recognizing an enzyme mutant with small improvement of activity.


Environmental degradation of microbial polyhydroxyalkanoates and oil palm-based composites.
This paper investigates the degradation of polyhydroxyalkanoates and its biofiber composites in both soil and lake environment. Time-dependent changes in the weight loss of films were monitored. The rate of degradation of poly(3-hydroxybutyrate) [P(3HB)], poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-23 mol% 4HB)] and poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-4-hydroxybutyrate) [P(3HB-co-9 mol% 3HV-co-19 mol% 4HB)] were investigated. The rate of degradation in the lake is higher compared to that in the soil. The highest rate of degradation in lake environment (15.6% w/w week(-1)) was observed with P(3HB-co-3HV-co-4HB) terpolymer. Additionally, the rate of degradation of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-38 mol% 3HV)] was compared to PHBV biofiber composites containing compatibilizers and empty fruit bunch (EFB). Here, composites with 30% EFB displayed the highest rate of degradation both in the lake (25.6% w/w week(-1)) and soil (15.6% w/w week(-1)) environment.


Rural obesity, healthy weight and perceptions of risk: struggles, strategies and motivation for change.
To explore risk logics, embodiment (the interplay between the physical, social and subjective body) and issues related to adult obesity in remote New South Wales. Qualitative multiple-method design using semistructured interviews and visual aids (food and exercise palm cards) to explore the saliency of food and exercise options. A one-page demographic survey incorporated self-reported body mass index. A total of 19 rural adults (13 female; six male). Community in remote New South Wales, Australia. Thematic analysis revealed 14 major weight-related themes. Respondents raised numerous explanations for their weight gain, reported struggles with weight loss, revealed a range of motivations for weight loss and a variety of approaches to risk, not all of which are aligned to dominant health discourse. The need for realistic interventions incorporating social meaning and pleasure seeking is revealed. Obesity interventions promoting 'easy' healthy choices also need to acknowledge embodiment and social status linked to consumption. Interventions that ignore the complexity surrounding consumption (e.g. the interplay of social taste, group distinction and embodiment) will have lower relevance and effectiveness.


Retention mechanisms in reversed-phase chromatography. Stationary phase bonding density and solute selectivity.
Chromatographic selectivity for small, non-polar solutes has been determined as a function of monomeric octadecyl stationary phase bonding density over the range 1.74-4.07 mumol/m2. Phenyl or shape selectivity increases with increasing bonding density, whereas methylene selectivity remains approximately constant. These findings are in agreement with the mean field statistical thermodynamic theory of Dill, which predicts that increased stationary phase chain density should lead to increased anisotropic chain ordering and increased solute-shape selectivity. These studies provide further evidence that partitioning, not adsorption, is the dominant mode of retention for small, non-polar molecules in reversed-phase liquid chromatography.


Standardization of amygdalohippocampectomy with intraoperative magnetic resonance imaging: preliminary experience.
Intraoperative magnetic resonance imaging (IMRI) is an extremely useful neurosurgical tool in surgeries in which the extent of resection is known to have a significant impact on outcome. Residual hippocampus is the most common cause of recurrent seizures after temporal lobectomy for medial temporal lobe epilepsy. Although the risk/benefit ratio of a policy of universal radical hippocampal resection is not known, we hypothesized that IMRI would aid in the intraoperative assessment of the extent of hippocampal resection and assist in accomplishing a complete hippocampectomy. Five consecutive patients with medically intractable medial temporal lobe epilepsy underwent a radical amygdalohippocampectomy as part of the their surgery for epilepsy. IMRI was used before surgery and after an initial resection. The quality of images was assessed. Postoperative MR images were evaluated by a radiologist to determine the extent of resection of the amygdala, hippocampus, and parahippocampal gyrus. There were no perioperative infections. After a mean follow-up of 10 months, all patients are seizure free. T(1)-weighted coronal intraoperative images were judged adequate at visualizing the medial structures in all patients. T(2) and fluid-attenuated inversion recovery (FLAIR) images did not provide useful information. Postoperative MR images indicated that a complete hippocampectomy had been achieved in all patients. IMRI is a useful adjunct in the surgical treatment of medial temporal lobe epilepsy and perhaps the most reliable method of standardizing a complete hippocampectomy. T(1)-weighted coronal images are the most helpful sequence.


Classification of acute spinal cord injury, neurological evaluation, and neurosurgical considerations.
This article provides an overview of the classification of acute spinal cord injuries as well as the description of the pathophysiology and neuroanatomy of the most commonly traumatized areas of the spinal cord. The essentials of the neurological examination relative to spinal cord injuries is discussed and the specific abnormalities found in patients with spinal cord syndromes. Management principles are briefly summarized.


Anxiety disorders and inflammation in a large adult cohort.
Although anxiety disorders, like depression, are increasingly being associated with metabolic and cardiovascular burden, in contrast with depression, the role of inflammation in anxiety has sparsely been examined. This large cohort study examines the association between anxiety disorders and anxiety characteristics with several inflammatory markers. For this purpose, persons (18-65 years) with a current (N=1273) or remitted (N=459) anxiety disorder (generalized anxiety disorder, social phobia, panic disorder, agoraphobia) according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and healthy controls (N=556) were selected from the Netherlands Study of Depression and Anxiety. In addition, severity, duration, age of onset, anxiety subtype and co-morbid depression were assessed. Inflammatory markers included C-reactive protein (CRP), interleukin (IL)-6 and tumor-necrosis factor (TNF)-α. Results show that after adjustment for sociodemographics, lifestyle and disease, elevated levels of CRP were found in men, but not in women, with a current anxiety disorder compared with controls (1.18 (s.e.=1.05) versus 0.98 (s.e.=1.07) mg l(-1), P=0.04, Cohen's d=0.18). No associations were found with IL-6 or TNF-α. Among persons with a current anxiety disorder, those with social phobia, in particular women, had lower levels of CRP and IL-6, whereas highest CRP levels were found in those with an older age of anxiety disorder onset. Especially in persons with an age of onset after 50 years, CRP levels were increased compared with controls (1.95 (s.e.=1.18) versus 1.27 (s.e.=1.05) mg l(-1), P=0.01, Cohen's d=0.37). In conclusion, elevated inflammation is present in men with current anxiety disorders. Immune dysregulation is especially found in persons with a late-onset anxiety disorder, suggesting the existence of a specific late-onset anxiety subtype with a distinct etiology, which could possibly benefit from alternative treatments.