Combine body mass index and body fat percentage measures to improve the accuracy of obesity screening in young adults.
Obesity screening among young adult groups is meaningful. Body mass index (BMI) is limited to discriminate between fat and lean mass. Asian young adult group tends to have lower BMI and higher body fat percentage (BFP) than other ethnic groups. Accuracy of obesity screening by commonly used BMI criteria is unclear in young Taiwanese population. A total of 894 young adults (447 males and 447 females) aged 20-26 were recruited. BMI, regional fat percentage and BFP determined by bioelectrical impedance analysis (BIA) were measured. BMI cutoff points were based on the criteria adopted by the Ministry of Health and Welfare in Taiwan. Cutoff points of low or high BFP were defined as 24% in men and 31.4% in women. Prevalence of BFP defining obesity was 14.8% in young men and 27.3% in young women. 23.2% of young men and only 8.3% of young women were classified to overweight or obesity categories according to the BMI criteria. Disagreement was noticed mainly among overweight males and normal weight females. 68.7% of BMI defining overweight young men had low BFP; however, 29.7% of young women of BMI defining normal group had high BFP. Up to 69.7% of young women with high BFP would be missed by BMI category only. Disagreement between BMI and BFP was significant among young adults, especially young women. We suggest combining BMI and BIA for obesity and overweight screening in Asian young adults.


Polymethyl methacrylate intraocular lens opacification 20 years after cataract surgery: A case report in a tertiary eye hospital in Saudi Arabia.
Snowflake degeneration is a slow progressive opacification of polymethyl methacrylate (PMMA) intraocular lenses (IOLs). This late postoperative complication can occur a decade or later after implantation. The deposits are composed of IOL materials that tend to aggregate centrally. There is a relative paucity of the literature on snowflake degeneration of IOLs. Symptoms can range from mild visual disturbance to significant loss of visual acuity. In cases of opacification after IOL implantation, the different diagnosis should include snowflake degeneration to prevent surgical intervention such as lens exchange or explantation unless clinically warranted. We report a case of late optical opacification of a PMMA IOL, the clinical diagnosis and treatment that increased best corrected vision.


Combining methionine-PET and MRI fluid-attenuated inversion-recovery mismatch to determine glioma molecular subtype.
11 C-methionine (MET)-PET is a useful tool in neuro-oncology. The T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign on MRI is a characteristic finding in lower grade gliomas with isocitrate dehydrogenase (IDH) mutations and the absence of the 1p/19q codeletion; however, the T2-FLAIR mismatch sign has low sensitivity in differentiating gliomas and does not aid in identifying glioblastomas with IDH mutations. We therefore investigated the efficacy of the combination of the T2-FLAIR mismatch sign and MET-PET for accurately determining the molecular subtype of gliomas of all grades. The present study comprised 208 adult patients diagnosed with supratentorial glioma confirmed by molecular genetics and histopathology. The ratio of the maximum lesion MET accumulation to the mean normal frontal cortex MET accumulation (T/N) was measured. The presence or absence of the T2-FLAIR mismatch sign was determined. The presence or absence of the T2-FLAIR mismatch sign and the MET T/N ratio were compared between glioma subtypes to evaluate individual and combined utility in identifying gliomas with IDH mutations and no 1p/19q codeletion (IDHmut-Noncodel) or gliomas with IDH mutations (IDHmut). The addition of MET-PET to MRI for the presence of the T2-FLAIR mismatch sign improved diagnostic accuracy, with the area under the curve values increasing from .852 to .871 for IDHmut-Noncodel and from .688 to .808 for IDHmut. The combination of the T2-FLAIR mismatch sign and MET-PET may provide improved diagnostic utility in differentiating gliomas according to molecular subtype, particularly in determining IDH mutation status.


Adoption and Outcomes of Holmium Laser Enucleation of the Prostate in the United States.
To investigate the utilization of holmium laser enucleation of the prostate (HoLEP) using a large real-world cohort. We compare the safety, readmission, and retreatment rates of HoLEP to other widely used endoscopic surgical interventions for benign prostatic hyperplasia (BPH) including transurethral resection of the prostate (TURP), photoselective vaporization of the prostate, and prostatic urethral lift. Men who underwent endoscopic treatments for BPH from 2000 to 2019 were identified in the Premier Healthcare Database (n = 218,793). We compared the relative proportion of each procedure performed and annual physician volume data to identify trends in adoption and utilization. Readmission and retreatment rates were determined at both 30- and 90-days postoperation. Multivariable logistic regression was used to assess the association between procedure type and outcomes. HoLEP accounted for 3.2% (n = 6967) of all the BPH procedures performed between 2000 and 2019 and increased from 1.1% of the procedures in 2008 to 4% in 2019. Patients undergoing HoLEP had lower odds of 90-days readmission compared to TURP (Odds ratio (OR) 0.87, p = 0.025). HoLEP had similar odds of retreatment compared to TURP at both 1-year (OR 0.96, p = 0.7) and 2-years (OR 0.98, p = 0.9), while patients undergoing photoselective vaporization of the prostate and prostatic urethral lift were more likely to retreat within 2-years (OR 1.20, P < 0.001; OR 1.87, P < 0.001). HoLEP is a safe therapy for BPH with lower readmission and comparable retreatment rates to the gold standard TURP. Despite this, the utilization of HoLEP has lagged behind other endoscopic procedures and remains low.


Oral Ganglioside Supplement Improves Growth and Development in Patients with Ganglioside GM3 Synthase Deficiency.
Ganglioside GM3 synthase is a key enzyme involved in the biosynthesis of gangliosides. GM3 synthase deficiency (GM3D) causes an absence of GM3 and all downstream biosynthetic derivatives. The affected individuals manifest with severe irritability, intractable seizures, and profound intellectual disability. The current study is to assess the effects of an oral ganglioside supplement to patients with GM3D, particularly on their growth and development during early childhood. A total of 13 young children, 11 of them under 40 months old, received oral ganglioside supplement through a dairy product enriched in gangliosides, for an average of 34 months. Clinical improvements were observed in most children soon after the supplement was initiated. Significantly improved growth and development were documented in these subjects as average percentiles for weight, height, and occipitofrontal circumference increased in 1-2 months. Three children with initial microcephaly demonstrated significant catch-up head growth and became normocephalic. We also illustrated brief improvements in developmental and cognitive scores, particularly in communication and socialization domains through Vineland-II. However, all improvements seemed transient and gradually phased out after 12 months of supplementation. Gangliosides GM1 and GM3, although measureable in plasma during the study, were not significantly changed with ganglioside supplementation for up to 30 months. We speculate that the downstream metabolism of ganglioside biosynthesis is fairly active and the potential need for gangliosides in the human body is likely substantial. As we search for new effective therapies for GM3D, approaches to reestablish endogenous ganglioside supplies in the affected individuals should be considered.


Targeting the proprotein convertase subtilisin/kexin type 9 for the treatment of dyslipidemia and atherosclerosis.
Hypercholesterolemia is a major risk factor for cardiovascular diseases, increasing the incidence of myocardial infarction and death. Statin-induced lowering of low-density lipoprotein cholesterol (LDL-C) reduces cardiovascular morbidity and mortality. However, many individuals treated with statins do not achieve their target levels of LDL-C, and thus, LDL-associated residual risk remains. Gain-of-function mutations of the proprotein convertase subtilisin/kexin type 9 (PCSK9) are associated with hypercholesterolemia and increased risk of cardiovascular events. Conversely, loss-of-function mutations are linked to low plasma LDL-C levels and a reduction of cardiovascular risk without known unwanted effects on individual health. Experimental studies have revealed that PCSK9 reduces the hepatic uptake of LDL-C by increasing the endosomal and lysosomal degradation of LDL receptors (LDLR). Low intracellular cholesterol levels in response to statin treatment activate the sterol regulatory element-binding protein-2 (SREBP-2), resulting in coexpression of LDLR and PCSK9. Although this self-regulatory mechanism contributes to maintain cholesterol homeostasis preventing excessive cholesterol uptake, it may limit the therapeutic effect of statins. A number of clinical studies have demonstrated that inhibition of PCSK9 alone and in addition to statins potently reduces serum LDL-C concentrations. Moreover, experimental studies indicate that PCSK9 might accelerate atherosclerosis by promoting inflammation, endothelial dysfunction, and hypertension by mechanisms independent of the LDLR. Further research is needed to characterize the potential therapeutic and to rule out unwanted off-target effects of PCSK9 inhibition. In this review we elucidate the role of PCSK9 in lipid homeostasis, highlight the impact of PCSK9 on atherosclerosis, and summarize current therapeutic strategies targeting PCSK9.


Dehydration-responsive features of Atrichum undulatum.
Drought is an increasingly important limitation on plant productivity worldwide. Understanding the mechanisms of drought tolerance in plants can lead to new strategies for developing drought-tolerant crops. Many moss species are able to survive desiccation-a more severe state of dehydration than drought. Research into the mechanisms and evolution of desiccation tolerance in basal land plants is of particular significance to both biology and agriculture. In this study, we conducted morphological, cytological, and physiological analyses of gametophytes of the highly desiccation-tolerant bryophyte Atrichum undulatum (Hedw.) P. Beauv during dehydration and rehydration. Our results suggested that the mechanisms underlying the dehydration-recovery cycle in A. undulatum gametophytes include maintenance of membrane stability, cellular structure protection, prevention of reactive oxygen species (ROS) generation, elimination of ROS, protection against ROS-induced damage, and repair of ROS-induced damage. Our data also indicate that this dehydration-recovery cycle consists not only of the physical removal and addition of water, but also involves a highly organized series of cytological, physiological, and biochemical changes. These attributes are similar to those reported for other drought- and desiccation-tolerant plant species. Our findings provide major insights into the mechanisms of dehydration-tolerance in the moss A. undulatum.


The effect of intraoperative goal-directed crystalloid versus colloid administration on perioperative inflammatory markers - a substudy of a randomized controlled trial.
Excessive perioperative fluid administration may result in iatrogenic endothelial dysfunction and tissue edema, transducing inflammatory markers into the bloodstream. Colloids remain longer in the circulation, requiring less volume to reach similar hemodynamic endpoints compared to crystalloids. Thus, we tested the hypothesis that a goal-directed colloid regimen attenuates the inflammatory response compared to a goal-directed crystalloid regime. Patients undergoing moderate- to high-risk open abdominal surgery were randomly assigned to goal-directed lactated Ringer's solution (n = 58) or a hydroxyethyl starch 6% 130/0.4 (n = 62) fluid regimen. Our primary outcome was perioperative levels of pro- and anti-inflammatory cytokines. Secondary outcome was perioperative levels of white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT) and lipopolysaccharide-binding protein (LBP). Measurements were performed preoperatively, immediate postoperatively, on postoperative day one, two and four. The areas under the curve of Interleukin (IL) 6 (p = 0.60), IL 8 (p = 0.46), IL 10 (p = 0.68) and tumor necrosis factor α (p = 0.47) levels did not differ significantly between the groups. WBC, CRP and PCT values were also comparable. LBP, although significantly higher in the crystalloid group, remained in the normal range. Patients assigned to crystalloids received a median (IQR) amount of 3905 mL (2880-5288) of crystalloid. Patients assigned to colloids received 1557 mL (1207-2116) of crystalloid and 1250 mL (750-1938) of colloid. Cytokine and inflammatory marker levels did not differ between goal-directed crystalloid and colloid administration after moderate to high-risk abdominal surgery. ClinicalTrials.gov ( NCT00517127 ). Registered 16th August 2007.


The TRH-related peptide pyroglutamyglutamylprolinamide is present in human semen.
We have recently identified a novel peptide in the rabbit prostate complex which cross-reacts with an antibody to thyrotrophin-releasing hormone (TRH) and has the structure pGlu-Glu-ProNH2. In the present study, high concentrations of a TRH-related tripeptide and also a polypeptide (10-12 kDa) containing a TRH-immunoreactive peptide at its C-terminus were detected in human semen. The low molecular mass TRH-like peptide and the immunoreactive fragment from the polypeptide were isolated from human semen and shown to have identical structures. Amino acid analysis suggested compositions Glx2, Pro1, and after mild acid hydrolysis, the same sequence, Glu-Glu-Pro, was established for the two peptides. Fast atom bombardment (FAB) mass spectrometry yielded a pseudomolecular ion (M + H)+ of 355.38 which was identical to that of the synthetic peptide pGlu-Glu-ProNH2. The data demonstrate that human semen contains the TRH-like peptide pyroglutamylglutamylprolinamide and also a polypeptide terminating in the sequence Gln-Glu-ProNH2.


Low-oxidation-state Ru sites stabilized in carbon-doped RuO2 with low-temperature CO2 activation to yield methane.
The generation of methane fuel using surplus renewable energy with CO2 as the carbon source enables both the decarbonization and substitution of fossil fuel feedstocks. However, high temperatures are usually required for the efficient activation of CO2. Here we present a solid catalyst synthesized using a mild, green hydrothermal synthesis that involves interstitial carbon doped into ruthenium oxide, which enables the stabilization of Ru cations in a low oxidation state and a ruthenium oxycarbonate phase to form. The catalyst shows an activity and selectivity for the conversion of CO2 into methane at lower temperatures than those of conventional catalysts, with an excellent long-term stability. Furthermore, this catalyst is able to operate under intermittent power supply conditions, which couples very well with electricity production systems based on renewable energies. The structure of the catalyst and the nature of the ruthenium species were acutely characterized by combining advanced imaging and spectroscopic tools at the macro and atomic scales, which highlighted the low-oxidation-state Ru sites (Run+, 0 < n < 4) as responsible for the high catalytic activity. This catalyst suggests alternative perspectives for materials design using interstitial dopants.


Protection of cattle against Babesia major by the inoculation of irradiated piroplasms.
Two experiments were carried out on Babesia major in splenectomised calves. In the first one, the parasite was titrated and a linear relationship was observed between infective dose (10(2)--10(7) parasites) and onset of disease. In the second experiment aliquots of 1.2 X 10(10) parasites were irradiated at doses of 24, 28, 32, 36 and 40 krads and inoculated into groups of calves, while control calves received 1.2 X 10(7) or 1.2 X 10(4) parasites. Animals which received parasites irradiated at 24 or 28 krads had mild reactions and were immune to homologous challenge. Animals receiving parasites irradiated at the higher dose levels had limited ability to resist the challenge.


Molecular detection of opportunistic premise plumbing pathogens in rural Louisiana's drinking water distribution system.
Opportunistic premise plumbing pathogens (OPPPs) in drinking water distribution systems are responsible for causing numerous infections such as Legionnaires' disease and pneumonia through the consumption of contaminated drinking water. The incidence of opportunistic pathogens and the number of individuals at risk of contracting infections caused by these OPPPs in drinking water has risen drastically in the past decade. Preflush and postflush water samples were collected from 64 houses in a rural town in northeast Louisiana to determine drinking water quality in terms of understanding abiotic and biotic factors on potential proliferation of OPPPs. Physical and chemical water quality parameters, such as pH, temperature, dissolved oxygen, salinity, and specific conductance were also measured. The quantitative polymerase chain reaction (qPCR) results indicated that Legionella spp. had the highest prevalence and was found in 46/64 samples (72%), followed by Mycobacterium spp. which was found in 43/64 samples (67%), E. coli in 31/64 samples (48%) and, Naegleria fowleri in 4/64 samples (6%) respectively. The results indicate the persistence of Legionella spp. DNA marker in these water samples.


Cysteine-stabilized αβ defensins: From a common fold to antibacterial activity.
Antimicrobial peptides (AMPs) seem to be promising alternatives to common antibiotics, which are facing increasing bacterial resistance. Among them are the cysteine-stabilized αβ defensins. These peptides are small, with a length ranging from 34 to 54 amino acid residues, cysteine-rich and extremely stable, normally composed of an α-helix and three β-strands stabilized by three or four disulfide bonds and commonly found in several organisms. Moreover, animal and plant CSαβ defensins present different specificities, the first being mainly active against bacteria and the second against fungi. The role of the CSαβ-motif remains unknown, but a common antibacterial mechanism of action, based on the inhibition of the cell-wall formation, has already been observed in some fungal and invertebrate defensins. In this context, the present work aims to group the data about CSαβ defensins, highlighting their evolution, conservation, structural characteristics, antibacterial activity and biotechnological perspectives.


Age-related changes in human vitreous structure.
Changes in vitreous structure that occur with aging are important in the pathogenesis of vitreous liquefaction (synchisis senilis), vitreous detachment, and retinal disease. Vitreous morphology was studied in 59 human eyes post-mortem using dark-field horizontal slit illumination of the entire dissected vitreous. In many individuals younger than 30 years, the vitreous was homogeneous in structure. Middle-aged individuals had macroscopic fibers in the central vitreous, which coursed anteroposteriorly and inserted into the vitreous base and the vitreous cortex, posteriorly. During senescence, the vitreous volume was reduced, the vitreous body was collapsed (syneresis), and the fibers were thickened, tortuous, and surrounded by liquid vitreous. This sequence of age-related changes probably results from a progressive reorganization of the hyaluronic acid and collagen molecular networks. Characterization of the molecular events underlying these changes will elucidate the mechanisms of the phenomena of synchisis, syneresis, and detachment, and may provide methods with which to prevent or induce vitreous detachment prophylactically.


A comparison of three neonatal resuscitation devices.
Ventilation during neonatal resuscitation involves the use of self-inflating bags, flow-inflating bags, and T-piece resuscitators. The ability of operators to deliver desired peak inspiratory pressures (PIP), positive end expiratory pressures (PEEP), prolonged inflations and the length of time to transition between different pressures has not been compared for all three of these devices. To compare the ability of neonatal resuscitation personnel to deliver predetermined ventilation interventions using these devices in advance of a clinical trial of neonatal resuscitation. We studied 31 operators (neomatologists, neonatal respiratory therapists, neonatal fellows, a pediatrician, pediatric residents, neonatal nurse practitioners, and neonatal nurses) using a T-piece resuscitator (Neopuff), Fisher and Paykel Healthcare, Auckland, New Zealand), a self-inflating bag (Baby Blue II, Vital Signs, Totowa, NJ), and a flow-inflating bag (Model E191 Anesthesia Associates, San Marcos, CA). The self-inflating bag was tested with and without the manufacturer's PEEP valve. Using a continuous pressure recording system and a neonatal manikin, we evaluated the ability to deliver a consistent PIP of 20 or 40 cmH2O and a PEEP of 5 cmH2O during 30 s of ventilation, the ability to maintain a 5 s inflation at a PIP of 20 cmH2O and the time to transition from a PIP of 20 to 40 cmH2O. Each device was evaluated with and without a qualitative CO2 detector (Pedicap) Nellcor Pleasanton, CA). The T-piece resuscitator delivered the desired PIP more precisely and consistently compared with the self-inflating bag at a target of 20 cmH2O (maximum PIP 20.7 cmH2O, S.D.=0.8 versus 24.7 cmH2O, S.D.=2.8; p<0.001). At a target of 40 cmH2O, the maximum pressure delivered with the T-piece resuscitator was significantly less than both the flow-inflating bag and the self-inflating bag (39.7 cmH2O, S.D.=2.1 versus 44 cmH2O, S.D.=3.3 versus 45.3 cmH2O, S.D.=4.7; p<0.001). It took significantly longer to increase the PIP from 20 to 40 cmH2O using the T-piece resuscitator compared to the self-inflating bag or the flow-inflating bag (5.7 s versus 2.2 s versus 1.8 s; p<0.001), and three operators could not make the transition in the allotted 15 s time limit. During the 5 s prolonged inflation, the T-piece resuscitator and the flow-inflating bag maintained a pressure greater than 18 cmH2O for a longer time than the self-inflating bag (4 s versus 3.7 s versus 2.2 s; p<0.001). The self-inflating bag with the PEEP valve in place provided significantly less PEEP than both the T-piece resuscitator and the flow-inflating bag (3.6 cmH2O versus 4.4 cmH2O versus 4.4 cmH2O; p<0.005). The Pedicap did not significantly affect any of the observed results, and there were no consistent operator differences between different disciplines or years of experience. The T-piece resuscitator delivered the desired pressures more accurately, but required greater time to increase the PIP from 20 to 40 cmH2O. It was difficult to maintain a prolonged inflation and deliver the desired PEEP with the self-inflating bag even with the PEEP valve in place. There is a need for improvement in the design and function of current manual resuscitation devices and for prospective trials to evaluate the optimal method of bag and mask ventilation during resuscitation of the newborn infant.


Exposure to bisphenol A induces dysfunction of insulin secretion and apoptosis through the damage of mitochondria in rat insulinoma (INS-1) cells.
Bisphenol A (BPA) is widely used in plastic products, through which humans are exposed to it. Accumulating evidence suggests that BPA exposure is associated with β-cell dysfunction. Mitochondrial defects can cause impairment and failure of β cells, but there is little information about the effects of BPA on the mitochondrial function of β cells. In this study, we assessed the role of mitochondria-mediated mechanisms underlying BPA-induced β-cell dysfunction and resulting β-cell apoptosis. INS-1 cells were cultured with 0, 0.0020, 0.020, 0.20, or 2.0 μM BPA. Cell viability, glucose-stimulated insulin secretion (GSIS), and mitochondrial function were examined. The mitochondrial apoptotic pathway was also analyzed at molecular level. We found that BPA suppressed cell viability and disturbed GSIS in a dose-dependent manner. Positive Annexin- propidium iodide (PI) staining and altered expression of Bcl-2 family members and caspases in INS-1 cells indicated that the cells progressively became apoptotic after BPA exposure. Additionally, BPA-induced apoptosis was associated with mitochondrial defects in β cells, as evidenced by depletion of ATP, release of cytochrome c, loss of mitochondrial mass and membrane potential, and alterations in expression of genes involved in mitochondrial function and metabolism. Taken together, these findings provide strong evidence that BPA triggers INS-1 cells dysfunction and apoptosis may be meditated via the mitochondrial pathway.


Contrast-enhanced sonography of malignant pediatric abdominal and pelvic solid tumors: preliminary safety and feasibility data.
Little information exists regarding pediatric contrast-enhanced US. To assess the safety and feasibility of contrast-enhanced US of pediatric abdominal and pelvic tumors. This prospective study included eight boys and five girls (mean age, 10.8 years) with abdominal or pelvic tumors. Cohorts of three subjects underwent US with perflutren contrast agent at escalating dose levels. Neurological and funduscopic examination, electrocardiography and continuous pulse oximetry were performed before and after contrast administration. Three radiologists independently scored six imaging parameters on pre- and postcontrast sonography. Inter-reviewer agreement was measured by the Kappa statistic. No neurological, retinal, electrocardiographical or pulse oximetry changes were attributable to the contrast agent. Two subjects reported minor, transient symptoms. Postcontrast US parameter scores improved slightly in 8 of 12 subjects. Postcontrast ultrasound inter-reviewer agreement improved slightly for detection of tumor margins (precontrast = 0.20, postcontrast = 0.26), local tumor invasion (precontrast = -0.01, postcontrast = 0.10) and adenopathy (precontrast = 0.35, postcontrast = 0.44). Although our sample size is small, perflutren contrast agents appear to be safe and well tolerated in children. Contrast-enhanced sonography of pediatric abdominal and pelvic tumors is feasible, but larger studies are needed to define their safety and efficacy in children.


Diversion neovaginitis after sigmoid vaginoplasty: endoscopic and clinical characteristics.
To assess the endoscopic characteristics of the sigmoid-derived neovagina, which have been scarcely described. Prospective observational study. University tertiary medical center. Patients that underwent sigmoid vaginoplasty. Patients were invited yearly to undergo neovaginoscopy and sigmoidoscopy, preceded by taking a medical history and physical examination, as routine follow-up. Endoscopic signs of neovaginal inflammation. Thirty-four patients with a sigmoid neovagina underwent a total of 43 combined neovaginoscopies and sigmoidoscopies. After a mean postoperative time of 23 months, the most notable endoscopic features of the sigmoid-derived neovagina comprised a diminished vascular pattern, edema, granularity, friability, decreased resilience, and erythema. In the control rectosigmoidoscopy images, no concurrent abnormalities were observed. When applying the MAYO score to the neovaginal images, 12 (35%) patients scored MAYO 0, 19 (56%) MAYO I, 3 (9%) MAYO II, and none MAYO III. The presence of neovaginal discharge and malodor correlated with inflammatory endoscopic alterations. The endoscopic appearance of a sigmoid segment after use in neovaginoplasty differs significantly from that of the remaining rectosigmoid. Inflammatory changes of the sigmoid-derived neovagina were observed in most patients. Clinically, the inflammatory changes appear similar to those encountered in diversion colitis.


A screen for over-secretion of proteins by yeast based on a dual component cellular phosphatase and immuno-chromogenic stain for exported bacterial alkaline phosphatase reporter.
To isolate over-secretors, we subjected to saturation mutagenesis, a strain of P.pastoris exporting E. coli alkaline phosphatase (EAP) fused to the secretory domain of the yeast α factor pheromone through cellular PHO1/KEX2 secretory processing signals as the α-sec-EAP reporter protein. Direct chromogenic staining for α-sec-EAP activity is non-specific as its NBT/BCIP substrate cross-reacts with cellular phosphatases which can be inhibited with Levulinic acid. However, the parental E(P) strain only exports detectable levels of α-sec-EAP at 69 hours and not within the 36 hour period post-seeding required for effective screening with the consequent absence of a reference for secretion. We substituted the endogenous cellular phosphatase activity as a comparative reference for secretion rate and levels as well as for colony alignment while elevating specificity and sensitivity of detection of the exported protein with other innovative modifications of the immuno-chromogenic staining application for screening protein export mutants. Raising the specificity and utility of staining for α-sec-EAP activity required 5 modifications including some to published methods. These included, exploitation of endogenous phosphatase activity, reduction of the cell/protein burden, establishment of the direct relation between concentrations of transcriptional inducer and exported membrane immobilized protein and concentrations of protein exported into growth media, amplification of immuno-specificity and sensitivity of detection of α-sec-EAP reporter enzyme signal and restriction of staining to optimal concentrations of antisera and time periods. The resultant immuno-chromogenic screen allows for the detection of early secretion and as little as 1.3 fold over-secretion of α-sec-EAP reporter protein by E(M) mutants in the presence of 10 fold -216 fold higher concentrations of HSA. The modified immuno-chromogenic screen is sensitive, specific and has led to the isolation of mutants E(M) over-secreting the α-sec-EAP reporter protein by a minimum of 50 fold higher levels than that exported by non-mutagenized E(P) parental strains. Unselected proteins were also over-secreted.


How to keep registered nurses working in New Zealand even as economic conditions improve.
Many registered nurses (RNs) increased their participation in the New Zealand health workforce during the Global Financial Crisis (GFC), resulting in low vacancy rates. However, based on the documented impact of improving economies, a mean RN age of about 50, and just-agreed substantive increases in RN pay rates, it is likely that many will soon leave or reduce the hours they work. This study aims to investigate whether improved financial security will encourage RNs to leave or reduce their work commitment and to identify the factors that influence such intentions. An exploratory study using a cross-sectional survey design. Data were collected in 2014-2015 via an e-survey of 2,910 RNs in New Zealand. Data were analysed by regression. We found that due to "burnout" and low "work engagement", both of which are strongly affected by workload and work-life interference, 22.6% of the RNs surveyed plan to leave work altogether and a further 32% plan to reduce their workforce participation when their financial situations improve. The findings justify the urgent cooperative development, implementation and evaluation of a comprehensive suite of RN 'retention' measures involving national nursing organisations, the RN regulator and health system employers and funders.


Visualization of antigenic proteins blotted onto nitrocellulose using the immuno-gold-staining (IGS) method.
A new and simple method for the detection of antigenic proteins blotted onto nitrocellulose was developed. After transfer of spinach stromal proteins and purified phosphoribulokinase immunolabeling was performed with phosphoribulokinase antiserum, followed by a) Protein A-labeled colloidal gold particles, and b) by horseradish peroxidase conjugated Protein A and substrate mixture. The Protein A-Gold method is at least twofold more sensitive than the Protein A-peroxidase procedure. Incubation of immunolabeled nitrocellulose replicas with 0.1 M glycine, pH 2.2, removes the antibody-Protein A-Gold complexes quantitatively without influencing the antigenicity of the immobilized proteins. The replicas can be re-used for immunostaining with other antisera. The versatile applicability of the immuno-gold-staining method suggests that it is a true alternative to the peroxidase assay.


Folate intake assessment: validation of a new approach.
To describe the performance characteristics and validate a folate-specific focused recall approach to estimating folate intake. In a cross-sectional study, folate-specific recalls were used to estimate subjects' average daily folate intake from seven days of dietary recall over a one-month period. This estimate was compared to an estimate of the average daily folate intake obtained using the Fred Hutchinson Cancer Research Center Food Frequency Questionnaire (FFQ) and to plasma folate and homocysteine concentrations. Subjects were women aged 21 to 47 years and were recruited from the university community. Thirty-three subjects were recruited, and 28 subjects completed the study. After an initial clinic visit, during which a baseline blood sample was collected for measurement of plasma folate and total homocysteine concentrations, subjects participated in focused dietary recall interviews by telephone and/or Internet (e-mail). At the end of the month, subjects completed the FFQ. Main outcome measures The main outcome measures were to describe how well the focused recalls were able to describe relative dietary folate intake as compared to the FFQ and if the focused recall method estimate correlated with plasma folate and homocysteine concentrations. Statistical analyses Estimated folate intakes were ranked by tertiles using the two dietary assessment approaches and the rankings were compared. The Spearman correlation test was used to compare the focused recall and the FFQ dietary data to plasma folate and homocysteine concentrations. Estimated folate intake inclusive of supplements was 411.4+/-192.8 (mean+/-SD) microg/day based on focused recalls and 458.5+/-221.5 microg/day based on the FFQ. Exclusive of supplements, estimated folate intake from the diet was 327.8+/-30.2 microg/day based on focused recalls and 373.5+/-155.6 microg/day based on the FFQ. The ranking comparison of focused recalls vs the FFQ demonstrated a concordance of 44% without supplements and 67% with supplements for the highest tertile, and 56% without supplements and 67% with supplements for the lowest tertile. Estimated folate intake based on focused recalls was correlated significantly with plasma homocysteine (r=-0.443, P<.02) and was marginally significantly correlated with plasma folate (r=0.354; P=.06) concentrations. A focused dietary recall approach is a useful method for collecting information on folate intake in women. Estimated folate intake based on the focused recall approach is reasonably correlated with plasma folate and total homocysteine concentrations even in this small sample of women. Accurate data on folate intake can form the basis of dietary counseling to increase intake of this important micronutrient in the target population of young women.


Haemolytic uraemic syndrome and the Thomsen Friedenreich antigen.
In three children with haemolytic uraemic syndrome (HUS), evidence of red cell polyagglutinability due to Thomsen Friedenreich antigen (T-antigen) exposure was demonstrated. This was suspected after difficulties in ABO typing and was confirmed using specific antisera. Further supportive evidence included elevation of plasma sialic acid, alteration in red cell surface charge and evidence of T-antigen exposure in the renal biopsy specimen of one patient. Although involvement of this antigen in the pathogenesis of HUS has been associated with a high mortality, all three children have made a complete recovery. With early recognition and subsequent avoidance of plasma products, prognosis of this condition may be improved.


Connected and isolated CH2 populations in acyl chains and its relation to pockets of confined water in lipid membranes as observed by FTIR spectrometry.
Analysis of the band corresponding to the frequency of vibrational symmetric stretching mode of methylene groups in the lipid acyl chains and the bands of water below and above the phase transition of different lipids by Fourier transform infrared spectroscopy gives strong support to the formation of confined water pockets in between the lipid acyl chains. Our measures and analysis consolidate the mechanism early proposed by Traüble, in the sense that water is present in kinks formed by trans-gauche isomers along the hydrocarbon tails. The formation of these regions depends on the acyl lipid composition, which determines the presence of different populations of water species, characterized by its degree of H bond coordination in fluid saturated or unsaturated lipids. The free energy excess due to the reinforcement of the water structure along few water molecules in the adjacencies of exposed membrane residues near the phase transition is a reasonable base to explain the insertion and translocation of polar peptides and amino acid residues through the biomembrane on thermodynamic and structural grounds.


Dermatoscopy and Reflectance Confocal Microscopy Correlations in Nonmelanocytic Disorders.
Dermatoscopy and in vivo reflectance confocal microscopy are noninvasive techniques that provide a horizontal approach, with an en face view of the skin structures. Both techniques assist in the clinical diagnosis of a variety of inflammatory and infectious cutaneous disorders. In many cases, they have shown concordance. Their combined use represents, in several instances, a promising option to reach the final diagnosis without the need for invasive procedures.


Do gastrointestinal symptoms vary with the menstrual cycle?
This systematic review presents both the physiological and symptom-based studies which have explored gastrointestinal variation across the menstrual cycle. Understanding this variation may be helpful in identifying the origin of pelvic pain, particularly as the symptoms associated with causes, such as endometriosis, also vary across the cycle. One-third of otherwise asymptomatic women may experience gastrointestinal symptoms at the time of menstruation, and almost 50% of women with irritable bowel syndrome report a perimenstrual increase in symptoms.


Effects of phytogenic feed additive based on thymol, carvacrol and cinnamic aldehyde on body weight, blood parameters and environmental bacteria in broilers chickens.
The aim of this study was to evaluate whether a phytogenic feed additive (PFA) based on essential oils such as carvacrol, thymol and cinnamic aldehyde, could be considered a replacement for antimicrobials used as growth promoters in broiler chickens, as well as to investigate its effect on total bacterial count, biochemical profiles, meat quality and meat fatty acid profile. A total of 240 broiler chicks were randomly distributed into 4 groups with 4 replicates of 15 animals each, as follow: T1 (basal diet only; the control group), T2 (basal diet supplemented with zinc bacitracin), T3 (basal diet with 0.5% of the PFA), T4 (basal diet with 1.0% of the PFA). The addition of 0.5% of the PFA improved live body weight of supplemented birds compared to the control group at 35 and 42 days of age, while the total bacterial count in the environment was reduced when 1.0% of the PFA was used. In addition, intestinal villi height and crypt depth suffered variations during the entire experiment in birds treated with both concentrations of the PFA and zinc bacitracin. Total erythrocyte counts were higher on days 14, 28 and 42 in both treated groups (PFA) compared to the control group, as well as hemoglobin content on days 28 and 42. On the other hand, leukocyte counts were lower on days 14, 28 and 42 due to reduced lymphocyte counts in both PFA treated groups compared to the control group. Serum levels of alanine aminotransferase (ALT) were lower in broilers fed with either concentration of PFA on day 14 of life, and the same was observed regarding aspartate aminotransferase (AST) in broiler treated with 0.5% of the PFA. Also, total protein and globulin levels were lower on days 14 and 28 in groups fed with phytogenic compared to the control group. Regarding meat quality, breast meat showed higher red intensity and shear force in groups fed with both concentrations of phytogenic compared to the control group, while weight loss by cooking was lower. Finally, 1.0% of phytogenic showed lower docosadienoic acid (C22:2) content in breast meat. In conclusion, results showed that the use of PFAs based on carvacrol and thymol may be considered an interesting alternative to increase broilers performance, replacing the use of antimicrobials as growth promoters, as well as an interesting alternative to reduce the total bacterial count in the environment of broiler chickens. Moreover, the diet containing phytogenic also showed hepaprotective effects but deserves attention regarding possible alterations on the immune response.


Amphiphilic spectroscopic probes utilizing metal chelates.
The synthesis and initial applications are reported for 1-[p-(palmitamido)-phenyl]ethylenedinitrilotetraacetic acid. The results demonstrate the versatility of this spectroscopic probe molecule, which allows choice of a particular technique for a particular system as well as use of multiple spectroscopic techniques for complementary information about hydrophobic regions in biological systems.


Mammographic screening: no reliable supporting evidence?
Much confusion is being generated by the conclusion of a recent review that "there is no reliable evidence that screening for breast cancer reduces mortality." In that review, however, there was no appreciation of the appropriate mortality-related measure of screening's usefulness; and correspondingly, there was no estimation of the magnitude of this measure. We take this measure to be the proportional reduction in case-fatality rate, and studied its magnitude on the basis of the only valid and otherwise suitable trial. We found reliable evidence of fatality reduction, apparently substantial in magnitude.


Comparison of the skin tumor initiating activity of 3-methylcholanthrene and 3,11-dimethylcholanthrene in mice.
The abilities of 3-methylcholanthrene (3-MC) and 3,11-dimethylcholanthrene (3,11-DMC) to initiate skin tumors in Sencar mice were determined by using a 2-stage system of tumorigenesis. 3,11-DMC was found to have very weak skin tumor initiating activity when compared to the potent activity of 3-MC. The only difference between 3-MC and 3,11-DMC is the substitution of a methyl group in position 11 which is part of the 'K-region' or the 'peri' position. From these results, we suggest that an unhindered peri position adjacent to an angular benzene ring is necessary for carcinogenic activity of 3-MC.


Beta adrenergic blockade in the treatment of sustained ventricular tachycardia or ventricular fibrillation.
The value of beta-blockers as antiarrhythmic drugs in patients with sustained VT or VF has received only little attention. This article summarizes the current state of knowledge regarding the identification of patients with sustained VT or VF with the highest benefit of beta-blockade. The antiarrhythmic mechanisms of beta-blockade and its efficacy as single or adjuvant therapy in patients with sustained VT or VF are reviewed. Current insights into the effects of beta-blockade in patients suffering from VT, in particular in the setting of heart failure, are discussed and future directions are considered.


Assembly of enveloped respiratory syncytial virus particles within the cytoplasm of infected Vero cells.
Electron microscopic examination of syncytia induced by a bovine respiratory syncytial virus strain in Vero cell cultures revealed the presence in the cytoplasm of assembled enveloped virus particles within inclusions of variable sizes. Moreover, budding virus particles were shown occasionally in the intracytoplasmic vesicles. These particles were filamentous in form, about 80-120 nm in diameter, variable in length, containing 12 nm diameter nucleocapsids, and looked like the extracellular particles budding at the plasma membranes. This is the first report on assembly of intracellular virus particles in cells infected by a member of the family Paramyxoviridae. Vero cell-dependent variations appear to be the factor leading to the defect in the late virus replication cycle.


A Case Report: Systemic Lymph Node Tuberculosis Mimicking Lymphoma on 18F-FDG PET/CT.
F-fluorodeoxyglucose positron emission tomography--an established modality for evaluating malignancies--exhibits increased uptake under inflammatory conditions. A 21-year-old man came to our hospital with persistent pain in his right lower quadrant of abdomen for more than 1 month, but had no diarrhea, fever, chills, weight loss, or other constitutional symptoms. Colonoscopy analysis showed no organic diseases in his colorectum. Ultrasound results revealed multiple enlarged lymph nodes in the bilateral neck, axilla, and groin. Positron emission tomography analysis was performed and showed intense ¹⁸F-fluorodeoxyglucose accumulation in the bilateral neck, supraclavicular, pulmonary hilar, mediastinum, gastric paracardial, and mesenterium lymph node. These findings were considered typical for lymphoma. To confirm the diagnosis, we obtained a diagnostic biopsy in the left supraclavicular lymph node. The diagnosis of tuberculosis was confirmed in the final pathology. This uncommon case underscores the necessity of considering lymph node tuberculosis as a possible differential diagnosis in lymphoma.


Effect of chlorides and sulfates on the performance of a Fe3+/H2O2 Fenton-like system in the degradation of methyl tert-butyl ether and its byproducts.
The effect of chloride and sulfate ions on the oxidation of methyl tert-butyl ether (MTBE) and its degradation products in a Fenton-like system was studied. Although both chloride and sulfate ions inhibited the decomposition of H202, chlorides were found to be the more effective inhibitor of MTBE degradation. In the presence of sulfates, MTBE decomposition can be attributed to oxidation not only by hydroxyl radicals, but also likely by SO4*- species. In the presence of chloride ions, it is possible that the dichloride radical is formed, which is less reactive than OH*. In the system under investigation, t-butyl alcohol was found to be the major byproduct, followed by t-butyl formate and acetone. The degradation rates of all intermediates and their inhibition in the presence of inorganic ions are similar to those obtained for MTBE, although their distributions are related to the concentrations of inorganic salts added.


Mepolizumab-a novel option for the treatment of hypereosinophilic syndrome in childhood.
Mepolizumab was originally intended as a therapeutic agent for atopic asthma in adults, and consequently, little is known about its use in children. Up to now, corticosteroids have formed the basis of the initial treatment of hypereosinophilic syndromes and are shown to be effective in most patients. To analyze the effect of mepolizumab in children is the aim of this study. We are reporting the experience of the effect of mepolizumab in 2 pediatric patients with hypereosinophilic syndrome that was not sufficiently controlled by other drugs. In addition, the literature regarding the treatment with mepolizumab in pediatric and adult patients is reviewed for the most important studies regarding safety and efficacy. Mepolizumab therapy showed in 2 pediatric patients with severe hypereosinophilic syndrome a safe and efficient therapeutic approach. No significant intolerances appeared. Furthermore, treatment with systemic corticosteroids was terminated, and therefore, severe side effects were avoided in our pediatric cases. Anti-IL-5 antibodies, which can be applied without substantial drug intolerances, are a new, safe, and effective treatment option for pediatric patients with hypereosinophilic syndrome.


The three-dimensional coupling mechanism in scoliosis and its consequences for correction.
In idiopathic scoliosis, the anterior spinal column has rotated away from the midline and has become longer through unloading and expansion of the intervertebral discs. Theoretically, extension of the spine in the sagittal plane should provide room for this longer anterior spinal column, allowing it to swing back towards the midline in the coronal and axial plane, thus reducing both the Cobb angle and the apical vertebral rotation. In this prospective experimental study, ten patients with primary thoracic adolescent idiopathic scoliosis (AIS) underwent MRI (BoneMRI and cVISTA sequences) in supine as well as in an extended position by placing a broad bolster, supporting both hemi-thoraces, under the scoliotic apex. Differences in T4-T12 kyphosis angle, coronal Cobb angle, vertebral rotation, as well as shape of the intervertebral disc and shape and position of the nucleus pulposus, were analysed and compared between the two positions. Extension reduced T4-T12 thoracic kyphosis by 10° (p < 0.001), the coronal Cobb angle decreased by 9° (p < 0.001) and vertebral rotation by 4° (p = 0.036). The coronal wedge shape of the disc significantly normalized and the wedged and lateralized nucleus pulposus partially reduced to a more symmetrical position. Simple extension of the scoliotic spine leads to a reduction of the deformity in the coronal and axial plane. The shape of the disc normalizes and the eccentric nucleus pulposus partially moves back to the midline.


MDCT evaluation of congenital mitral-aortic intervalvular fibrosa aneurysm: implications for the aetiology and differential diagnosis.
Mitral-aortic intervalvular fibrosa aneurysm is a rare disease whose aetiology remains a matter of debate. Here we present the youngest reported patient with the disease, a 6-month-old boy, without a history of infection, which supports a congenital origin as initially proposed. Multidetector-row CT (MDCT) surpassed echocardiography in delineating the intracardiac anatomical details with high spatial resolution, confirming the important problem-solving role of MDCT in the diagnosis of congenital heart disease.


The contributions and achievements on malaria control and forthcoming elimination in China over the past 70 years by NIPD-CTDR.
Although the past decades have seen a remarkable decrease in malaria-caused mortality and morbidity, the infection remains a significant challenge to global health. In the battle against malaria, China has gained notable feat and achievement since the 1940s through the efforts of several generations. Notably, China has not recorded a single indigenous malaria case since August 2016. The National Institute of Parasitic Diseases of the Chinese Center for Disease Control and Prevention (NIPD), as the only specialized institution for parasitic disease at the national level, has played a significant role in the malaria control, prevention, and elimination in China in the different historical periods. In order to transfer Chinese experiences on malaria control and elimination to other Low and Middle Income Countries (LMICs) and to improve global health collaboration, we have summarized and reviewed the contributions and achievements by the NIPD over the past 70 years, covering the epidemic situation; field investigation and laboratory experimental research on both parasite and vector; research and development on diagnostics, drugs, and insecticides; surveillance and response; technical and international. Support and cooperation. In addition, we also focus in particular on malaria retransmission risk, strategies on management of imported malaria cases and mobile populations, surveillance and response capacity to be maintained in post-elimination stage, challenges on diagnosis, drug resistance, and insecticide resistance as future concerns.


Microfauna community during pulp and paper wastewater treatment in a UNOX system.
This study characterized the microfauna community during treatment of pulp and paper wastewater in a UNOX system aerated with pure oxygen, and with a high organic loading rate (0.4±0.06kg BOD/kg MLSSday), low sludge retention time (3.73±0.33 day), and high oxygen concentration (≤20mg O2/L) in comparison to municipal treatment systems. In the aeration tank, temperatures were high, averaging 35.7°C (March-May), then 38.9°C (June-August). Effluent quality was acceptable: 180±22mg COD/L, 7.2±2.1mg BOD5/L, and 33±5mg TSS/L. At 35.7°C, 5 taxa were identified in the activated sludge: small flagellates (flagellates <20μm), attached ciliates (Vorticella infusionum, Vorticella octava), crawling ciliates (Chilodonella uncinata) and free-swimming ciliates (Sathrophilus muscorum). During this period, the SBI (Sludge Biotic Index) was 6-7, corresponding to Quality Class II. At 38.9°C, two taxa co-dominated (Vorticella infusionum, Sathrophilus muscorum). When Vorticella infusionum dominated, the SBI was 5 or 7 (Quality Class III/II); when Sathrophilus muscorum dominated, the SBI was 0 (Quality Class IV). Slight changes in the abundance of two opposing Madoni keygroups impeded proper classification of activated sludge. However, effluent quality remained the same, showing that these indicators of activated sludge quality do not always reflect effluent quality.


Optimal design of a single recombinant adeno-associated virus derived from serotypes 1 and 2 to achieve more tightly regulated transgene expression from nonhuman primate muscle.
Recombinant adeno-associated virus (rAAV) vector supports long-term transgene expression from skeletal muscle in most mammals, including human. In some instances, the requirement for tight control of the transgene expression is expected. The original tetracycline-dependent system using the rtTA (Dox-on) transactivator displayed a baseline activity in the off state but improved versions are now available and need to be evaluated in a single-rAAV-vector strategy. In the present study we cloned, in three different orientations, the two expression cassettes responsible for doxycycline-mediated transgene regulation and further evaluated the basal and inducible activity of the recently described rtTA2S-S2, rtTA2S-M2, and rtTA2S-M2nls transactivators. Evaluations were conducted in vivo in mice and nonhuman primates using the respective homologous erythropoietin cDNA as a reporter gene because of its sensitive detection by ELISA. The woodchuck hepatitis virus posttranscriptional regulatory element sequence was also introduced to enhance further the stringency with respect to basal activity in the absence of inducer.


Tuberculosis and pregnancy--Results of a study in a high prevalence area in London.
The aim of the study was to characterise the incidence, type and presentation of tuberculosis in pregnancy over a 5-year period in women booked for antenatal care in a District General Hospital located in a high prevalence area in London. We also aimed to identify any problems and difficulties in the diagnosis and management of tuberculosis associated with pregnancy. Retrospective review of computer records and hospital notes over a period of 5 years from January 1997 to December 2001. Demographic and clinical data were collected for all the cases identified. All women with tuberculosis who conceived on antituberculous treatment, or had onset of symptoms or diagnosis made in pregnancy or the immediate postpartum period (6 weeks), and booked for antenatal care at a District General Hospital located in an area of high prevalence for tuberculosis (52.2 per 100,000 population in Ealing, Hammersmith and Hounslow Health authority according to the National Tuberculosis Survey of England and Wales in 1998). Thirty-two women were identified over the 5-year period, giving an incidence of 252/100,000 deliveries. The number of cases increased from 3 in 1997 to 10 in each of 2000 and 2001. All of these women were from ethnic minorities and 88% of them were immigrants with the median interval from arrival in UK being 2 years. Fifty-three percent were diagnosed with extrapulmonary tuberculosis, 38% with pulmonary tuberculosis and 9% had both. The median duration of symptoms prior to presentation was 31 days (being longer in women with extrapulmonary tuberculosis); the longest was 10 years. The median interval from presentation of symptoms to diagnosis was 32 days and the majority of women started treatment immediately. The commonest reason for a delay in diagnosis was late presentation (52%), followed by non-specific symptoms (in 38%). There was a trend towards late presentation among recent immigrants (odds ratio 2.14, 95% confidence interval 0.44-10.53) and those having extrapulmonary tuberculosis (odds ratio 1.64, 95% CI 0.32-8.45). Most of the women (28/32) showed good compliance and a good response to treatment (31/32). Maternal outcomes were good with no serious morbidity or mortality. The majority of women delivered at term (28/32), while two delivered preterm and two women miscarried. There was no perinatal mortality. This is the largest recent series of pregnant women with tuberculosis in the UK. A high incidence of extrapulmonary tuberculosis was seen. The common causes for a delay in diagnosis were late presentation and non-specific symptoms. If recent immigrants from high prevalence areas who have been in the UK for less than 5 years were asked for symptoms suggestive of tuberculosis at the booking visit and through pregnancy, this might facilitate early diagnosis and treatment. The use of a symptom questionnaire at the booking visit for these women could be a method to alert both the women and health professionals involved in their care, to the symptoms of tuberculosis. With good compliance, there is a good response to treatment and favourable maternal and perinatal outcomes.


Modelling growth and bacteriocin production by Pediococcus acidilactici PA003 as a function of temperature and pH value.
To investigate the effect of pH and temperature on the cell growth and bacteriocin production of Pediococcus acidilactici PA003, a lactic acid bacterium isolated from traditionally fermented cabbage, the kinetic behaviour of P. acidilactici PA003 was simulated in vitro during laboratory fermentations by making use of MRS broth. Firstly, primary models were developed for cell growth, glucose consumption, lactic acid and bacteriocin production for a given set of environmental conditions. Based on primary models, further study was undertaken to fit secondary models to describe the influence of temperature and pH on microbial behaviour. The models were validated successfully for all components. The results from the cell yield coefficient for lactic acid production reflected the homofermentative nature of P. acidilactici PA003. Both cell growth and bacteriocin production were very much influenced by changes in temperature and pH. The optimal condition for specific growth rate and biomass concentration was almost the same at pH 6.5 and 35 °C. At 35 °C and pH 6.1, the maximal bacteriocin activity was also achieved. The kinetic models provide useful tools for elucidating the mechanisms of temperature and pH on the kinetic behaviour of P. acidilactici PA003. The information obtained in this paper may be very useful for the selection of suitable starter cultures for a particular fermentation process and is a first step in the optimization of food fermentation processes and technology as well.


Paracoccus oceanense sp. nov., isolated from the West Pacific.
A Gram-negative, short ovoid- to coccus-shaped, aerobic, motile, non-spore-forming bacterium (designated strain JLT1679(T)) was isolated from West Pacific. Cells have subpolar flagella, dividing by binary fission. Phylogenetic analyses based on 16S rRNA gene sequences showed that the strain belongs to branch of the evolutionary radiation occupied by the genus Paracoccus, family Rhodobacteraceae, order Rhodobacterales, class Alphaproteobacteria. The closest neighbours were Paracoccus stylophorae KTW-16(T) (97.1% similarity), Paracoccus caeni strain MJ17(T) (96.5% similarity), Paracoccus homiensis DD-R11(T) (96.0% similarity) and Paracoccus alcaliphilus JCM 7364(T) (95.8% similarity). The predominant cellular fatty acids of strain JLT1679(T) were summed feature 8 (18:1ω6c) (38.8%), C(18:0) (27.7%), C(16:0) (22.5%), and significant amounts of C(18:1) ω9c (5.1%), C(14:0) (3.8%) and C(18:1) ω7c 11-methyl (2.1%), were present. The predominant respiratory ubiquinone of strain JLT1679(T) was Q-10 and the DNA G + C content of strain JLT1679(T) was 59.5 mol%. The polar lipid profile consisted of a mixture of phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine and sphingoglycolipid. The isolate was distinguishable from members of the genus Paracoccus on the basis of phenotypic and biochemical characteristics. It is evident from the genotypic, chemotaxonomic and phenotypic data that strain JLT1679(T) represents a novel species of the genus Paracoccus, for which the name Paracoccus oceanense sp. nov. is proposed. The type strain is JLT1679(T) (= JCM 17768(T) = CGMCC 1.10831(T)).


Adult-acquired flatfoot deformity.
Adult-acquired flatfoot deformity (AAFD) is a known and recognized cause of pain and disability. Loss of PTT function is the most important contributor to AAFD, and its estimated prevalence is thought to be over 3%. This review aims to summarize the current literature and encompass recent advances regarding AAFD.


Stable attachment for herpes simplex virus penetration into human cells requires glycoprotein D in the virion and cell receptors that are missing for entry-defective porcine cells.
Clonal porcine kidney cell lines that are non-permissive for herpes simplex virus (HSV) infection produced five orders of magnitude less virus than human cells, contained heparan sulfate (HS), and are restricted only at HSV entry. By fluorescent activated cell sorting, we examined HSV attachments to porcine and human cells. Stable attachment to susceptible human embryonic lung (HEL) cells occurred with infectious wild-type virus, complemented gD or gH mutant viruses, or non-infectious virus lacking gH. On HEL cells, mutant virus lacking gD bound to heparan sulfate, but failed to stably bind. None of these viruses stably attached to SK6-A7 cells, one of the non-permissive porcine cell clones. However, HSV could replicate in these cells when entry was mediated by polyethylene glycol. These results confirm that, in neutral pH entry of HSV, (i) multiple attachments to HS and non-HS components lead to penetration, (2) stable attachment before penetration is one required function of gD, but not gH, and (3) for stable attachment, gD interacts directly, or indirectly through another viral or cellular component, with receptors that are present on human cells, but absent for entry-defective porcine cells. Easily propagated clonal porcine cells are a novel resource to investigate stable attachment, the molecular mechanisms of gD functions, and the viral and cellular components that allow HSV entry and spread.


Skin blood flow and its oscillatory components in patients with acute myocardial infarction.
Laser Doppler flowmetry (LDF) was used to determine the influence of acute myocardial infarction (AMI) and of successful reperfusion treatment on basal skin blood flow and its oscillatory components. Skin LDF was performed on all extremities in 58 patients 4-9 days after AMI (Killip class I), and in 71 healthy age- and sex-matched controls. Wavelet analysis was applied to evaluate oscillatory components within the interval 0.005-2 Hz. AMI patients had reduced mean flow (p < 0.01) and oscillatory components (p < 0.04) in all extremities. Reperfused (n = 40), compared to nonreperfused (n = 18), patients had higher mean flow and total spectral amplitude at all recording points. The difference was statistically significant only in legs (group median LDF in the left leg was 9.68 AU for reperfused and 5.71 AU for nonreperfused patients, p < 0.04, and 11.47 and 4.24 AU in the right leg, p < 0.01). Reperfused patients had significantly higher total spectral amplitude in both legs (p < 0.04). In AMI patients, reduced skin blood flow and its oscillatory components may reflect ongoing neurohumoral activation despite absence of clinically apparent heart failure. The reduction of blood flow and its oscillatory components was larger in nonreperfused AMI patients, although they had a comparable left ventricular function.


Modular affinity-labeling of the cytosine demethylation base elements in DNA.
5-methylcytosine is the most studied DNA epigenetic modification, having been linked to diverse biological processes and disease states. The elucidation of cytosine demethylation has drawn added attention the three additional intermediate modifications involved in that pathway-5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine-each of which may have distinct biological roles. Here, we extend a modular method for labeling base modifications in DNA to recognize all four bases involved in demethylation. We demonstrate both differential insertion of a single affinity tag (biotin) at the precise position of target elements and subsequent repair of the nicked phosphate backbone that remains following the procedure. The approach enables affinity isolation and downstream analyses without inducing widespread damage to the DNA.


Simplified and versatile access to low valent Ni complexes by metal-free reduction of NiII precursors.
The reduction of [Ni(DME)Cl2] with 2 equiv. of bis(trimethylsilyl)-1,4-tetramethyldihydropyrazine in the presence of a ligand L and an excess of olefin cleanly leads to [Ni(L)(alkene)2] complexes. When reduction is performed in the presence of 1,5-cyclooctadiene (COD), [Ni(COD)2] is obtained. Such an approach also allows access to the NiI dimer [Ni(bis(dicyclohexylphosphino)propane)Cl]2.


Shancigusins E-I, five new glucosides from the tubers of Pleione yunnanensis.
Five new glucosides, shancigusins E-I (1-5) were isolated from the tubers of Pleione yunnanensis (Rolfe) together with 18 known compounds. The structures of these compounds were determined by extensive analyses of their spectroscopic data.


Projections of faster onset and slower decay of El Niño in the 21st century.
Future changes in the seasonal evolution of the El Niño-Southern Oscillation (ENSO) during its onset and decay phases have received little attention by the research community. This work investigates the projected changes in the spatio-temporal evolution of El Niño events in the 21st Century (21 C), using a multi-model ensemble of coupled general circulation models subjected to anthropogenic forcing. Here we show that El Niño is projected to (1) grow at a faster rate, (2) persist longer over the eastern and far eastern Pacific, and (3) have stronger and distinct remote impacts via teleconnections. These changes are attributable to significant changes in the tropical Pacific mean state, dominant ENSO feedback processes, and an increase in stochastic westerly wind burst forcing in the western equatorial Pacific, and may lead to more significant and persistent global impacts of El Niño in the future.


Depot antipsychotic use in schizophrenia: an East Asian perspective.
Few studies have examined the use of depot antipsychotics in East Asian patients with schizophrenia. This study examined the prevalence of depot antipsychotic use and its clinical correlates. Across six East Asian countries and territories, 2399 patients with schizophrenia were surveyed using a standardized protocol. Depot antipsychotic medications were prescribed in 15.3% (n=368) of the patients, being the most common in Singapore, followed by Taiwan, Japan and China. Being on depot antipsychotic drugs was significantly associated with male gender (particularly in Taiwan and Japan), delusions in Japan, aggression, higher daily CPZ equivalent dose and co-prescription of anticholinergic drugs but less likely with disorganized speech (particularly in China) and negative symptoms (particularly in Japan and Singapore). On multivariate analysis, the significant associated factors were treatment setting, younger age, longer duration of illness, aggression and the lack of use of an oral, atypical antipsychotic. There was a wide variation in the prevalence of depot antipsychotic prescription, suggesting that it may not be guided by any recognizable principles and is more likely determined by local traditions and prescription culture. There is a need to re-examine the risk-benefit profile of each patient before deciding on the initiation or continuation of depot antipsychotic medication.


Predicting clinical outcomes using artificial intelligence and machine learning in neonatal intensive care units: a systematic review.
Advances in technology, data availability, and analytics have helped improve quality of care in the neonatal intensive care unit. To provide an in-depth review of artificial intelligence (AI) and machine learning techniques being utilized to predict neonatal outcomes. The PRISMA protocol was followed that considered articles from established digital repositories. Included articles were categorized based on predictions of: (a) major neonatal morbidities such as sepsis, bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, and retinopathy of prematurity; (b) mortality; and (c) length of stay. A total of 366 studies were considered; 68 studies were eligible for inclusion in the review. The current set of predictor models are primarily built on supervised learning and mostly used regression models built on retrospective data. With the availability of EMR data and data-sharing of NICU outcomes across neonatal research networks, machine learning algorithms have shown breakthrough performance in predicting neonatal disease.


Highly Enhanced Antitumor Immunity by a Three-Barreled Strategy of the l-Arginine-Promoted Nanovaccine and Gene-Mediated PD-L1 Blockade.
Weak T cell responses and immune checkpoints within tumors could be two key factors for limiting antitumor efficacy in the field of cancer immunotherapy. Thus, the combined strategy of tumor vaccines and immune checkpoint blockade has been widely studied and expected to boost antitumor immune responses. Herein, we first developed a two-barreled strategy to combine the nanovaccine with a gene-mediated PD-L1 blockade. On the one hand, polyethyleneimine (PEI) worked as a vaccine carrier to codeliver the antigen ovalbumin (OVA) and the adjuvant unmethylated cytosine-phosphate-guanine (CpG) to formulate the PEI/OVA/CpG nanovaccine through electrostatic binding, which realized both dendritic cell activation and antigen cross-presentation enhancement. On the other hand, the PD-L1 silence gene was loaded by PEI to form PEI/pshPD-L1 complexes, which were further in situ shielded by aldehyde-modified polyethylene glycol (OHC-PEG-CHO) via pH-responsive Schiff base bonds. The formed pshPD-L1@NPs could decrease PD-L1 expression on the tumor cells. However, such a combined two-barreled strategy improved feebly for tumor inhibition in comparison with monotherapy, exhibiting the antagonistic effect, which might be due to the limited T cell response enhancement in the tumor microenvironment. To solve this problem, we have further developed a three-barreled strategy to combine oral administration of l-arginine, which worked as an amplifier to induce robust T cell response enhancement, without causing the upregulation of other negative immune regulators. Superior antitumor behavior and tumor rechallenge protection were realized by the three-barreled strategy in B16F10-OVA (B16-OVA)-bearing mice. The unique three-barreled strategy we developed might offer a novel clinical therapeutic treatment.


A golden approach to ion channel inhibition.
Drugs are often used in combination and, for pharmacologists, the manner of their interactions can cast light on drug mechanisms and biological processes. Here we provide simplified descriptions of commonly used analytical methods for analysing drug combinations and describe a new and practical experimental solution to address the mechanistic question: 'Do two channel-blocking drugs bind at the same site?' We define two simple mathematical models that describe the effects of two channel blockers acting simultaneously at either the same (Syntopic Model) or different (Allotopic Model) binding sites within a channel pore. We find that the optimum concentrations of two drugs for distinguishing between the two models are related to the mathematical Golden Ratio.


Progestin only contraceptives and their use in adolescents: clinical options and medical indications.
Some adolescents use progestin only contraceptive products because of an underlying medical condition; others simply prefer them. Current options include pills, a long -acting intramuscular injection, an implant, and a progestin-releasing intrauterine device. Also available is Plan B, a progestin only emergency contraceptive option. Although these products vary in efficacy, they are generally safe and well tolerated by adolescents. The implants and intramuscular injections are particularly well suited for adolescent use because of their need for little compliance, well-tolerated adverse effect profile, and excellent efficacy rates.


Stage-specific expression of bone morphogenetic protein type I and type II receptor genes: Effects of follicle-stimulating hormone on ovine antral follicles.
We investigated the mRNA expression patterns of receptor genes for bone morphogenetic proteins-15 (BMP15) and growth differentiation factor-9 (GDF-9) in granulosa cells of sheep treated with FSH. The effects of FSH and estradiol (E2) on the regulation of BMPRII, BMPRIB and ALK-5 in ovine granulosa cells were also examined. Ovaries were collected on day 16 of the estrous cycle and granulose cells were harvested from follicles of two sizes (3-5 and >5mm in diameter). For in vitro studies, granulosa cells were obtained from follicles of 3-5mm in diameter and cultured in serum-free McCoy's 5A medium supplemented with different doses of FSH (0, 1, 5, 10ng/ml) or a combination of 5ng/ml FSH with 1ng/ml E2. Expression of BMPRII, BMPRIB and ALK-5 mRNA was estimated by quantitative real-time PCR. Our results demonstrated that BMPRII, BMPRIB and ALK-5 expression was significantly higher in the granulosa cells of large follicles than of small follicles. Treatment of granulose cells with FSH (1-10ng/ml) alone down-regulated the expression of BMPRIB (P<0.05). BMPRII and ALK-5 mRNA expression was not significantly different at an FSH concentration of 5ng/ml compared to control. A further increase in FSH (10ng/ml) down-regulated the expression of BMPRII and ALK-5 (P<0.05). The combination of FSH (5ng/ml) and E2 (1ng/ml) up-regulated the expression of BMPRII, BMPRIB and ALK-5 in granulose cells (P<0.05). Therefore, the present study establishes the expression levels of the receptor genes of BMP15 and GDF-9 and suggests that the expression of BMPRII, BMPRIB and ALK-5 may be regulated by FSH and E2 in ovine granulosa cells.


Vagus Nerve Stimulation Relives Irritable Bowel Syndrome and the Associated Depression via α7nAChR-mediated Anti-inflammatory Pathway.
The present study is designed to investigate the role of vagus nerve in the treatments of irritable bowel syndrome (IBS) and the associated central nervous system disorders. An IBS animal model was established by giving acetic acid and chronic-acute stress (AA-CAS) treatment in adult male Wistar rats. Subdiaphragmatic vagotomy (SDV) and vagus nerve stimulation (VNS) were performed to intervene the excitability of vagus nerve. Permeability of blood brain barrier (BBB) was measured and agonist and antagonist of α7 nicotinic acetylcholine receptor (α7nAChR) were used to explore the relevant mechanisms. AA-CAS treatment resulted in abnormal fecal output, increased visceral sensitivity, depressive-like behaviors, and overexpression of inflammatory mediators, all of which were reversed by VNS treatment. The effects of VNS could also be observed when α7nAChR agonist was applied. Whereas α7nAChR antagonist (methyllycaconitine, MLA) reversed VNS's effects. Interestingly, VNS also reduced the increased permeability of blood brain barrier (BBB) following AA-CAS treatment in IBS rats. SDV treatment only show temporary efficacy on AA-CAS-induced symptoms and had no effect on the permeability of BBB. The intestinal abnormalities and depressive symptoms in IBS rats can be improved by VNS treatment. This positive effect of VNS was achieved through α7nAChR-mediated inflammatory pathway and may also be associated with the decreased of BBB permeability.


Effects of graded exercise on blood pressure, heart rate, and plasma hormones in cardiac transplant recipients before and during antihypertensive therapy.
The effects of graded supine ergometry on blood pressure, heart rate, and plasma hormones were studied in 14 hypertensive heart transplant recipients before and after 2 weeks and 6 months of enalapril (20 mg/day) plus furosemide (20-80 mg/day) alone or combined with verapamil (120-360 mg/day). Each time, measurements were obtained at rest and at 25 and 50 W exercise. Antihypertensive therapy normalized blood pressure, while heart rate and the blood pressure response to exercise remained unaltered. Pretreatment resting plasma renin activity and catecholamine levels were normal, while atrial natriuretic factor and cyclic guanosine monophosphate concentrations were elevated. All hormones increased significantly with exercise. During treatment, plasma renin activity increased and atrial natriuretic factor and cyclic guanosine monophosphate levels decreased significantly, with a blunted exercise response; concentration of catecholamines increased significantly, with augmented exercise response. Thus, the chosen regimen allowed effective, lasting BP control in hypertensive transplant patients but was associated with significant changes in plasma hormones. Whereas the rise in plasma renin activity may be attributed to converting enzyme inhibition, the decreases in atrial natriuretic factor and cyclic guanosine monophosphate and increases in catecholamine levels seem to indicate marked changes in resting and particularly exercise hemodynamics during antihypertensive therapy.


Local Health Jurisdiction Staff Deliver Health Promotion to Small Worksites, Washington.
Worksites can serve as community sites for local health jurisdictions (LHJs) to assist with implementation of evidence-based interventions (EBIs) to prevent and control chronic diseases. To assess the feasibility and effectiveness of using LHJ staff to disseminate Connect to Wellness (CtW), an effective dissemination package for increasing implementation of EBIs for chronic disease control by small worksites. Single-arm, multisite intervention trial, with measurement at baseline, after 6 months of intervention, and after a maintenance period of 6 months. Six geographically dispersed counties in Washington State. Target worksites had 20 to 250 employees. Nine staff members from 6 LHJs delivered CtW to 35 worksites. Connect to Wellness seeks to increase worksites' implementation of 14 EBIs classified as communication, policy, or program approaches to increasing 4 behaviors: cancer screening, healthy eating, physical activity, and tobacco cessation. Evidence-based intervention implementation measured on a scale from 0% to 100%. Participating worksites showed a significant increase (P < .001, t test) in total mean implementation scores from baseline (33%) to 6-month follow-up (47%). Increases in implementation for communications, policy, healthy eating, and tobacco EBIs were statistically significant at 6 months and maintained at 12 months. Increased implementation at 6 months of a group physical activity program was not sustained after the program became unavailable, and total implementation scores at 12 months (38%) showed little change from baseline. Local health jurisdiction-delivered CtW increased worksites' implementation of EBIs at 6 months, and increased implementation in communication, policy, healthy eating, and tobacco was maintained at 12 months. This package, delivered by LHJ staff working part-time on CtW, was nearly as successful as prior delivery by staff working full-time on CtW.


Testing the safety of Baxter continuous cardiac output monitoring system.
The safety of a new continuous cardiac output monitoring system, recently introduced by Baxter Healthcare Corporation's Edwards Critical-Care Division, was evaluated in normal sheep. The study compared the biocompatibility and safety of the Vigilance CCO Monitoring System, which employs a continuous cardiac output (CCO) catheter with Baxter Edward's standard Paceport pulmonary artery catheter. The CCO catheter, which monitors hemodynamic pressures and provides continuous measurement of cardiac output based on the thermodilution principle, contains a thermal filament that is powered and controlled by a unique cardiac output monitor. Parameters were measured periodically in conscious animals and complete necropsies were performed after each study. Time Control, Paceport, and four CCO groups were studied. Selected groups were studied for 3 days (acute), 7 days (subacute), and/or 4 weeks after 3 days of continuous use (recovery). Results showed no significant differences between the CCO and Paceport catheters in any of the parameters studied. On gross pathology, observations were similar. The only difference between catheters were microscopic findings of focal subendothelial or subendocardial changes correlated with areas that could have come into contact with the CCO catheter. In acute groups, these changes consisted of a localized myofiber degeneration or necrosis, while in subacute and recovery groups, consisted only of fibrosis. None of the changes were clinically significant. Thus, the CCO catheter, used in conjunction with the Vigilance CCO Monitoring System, appears to pose no additional risk over a standard Paceport catheter in normal sheep after continuous use for up to 7 days.


Eicosanoid synthesis in human peritoneal macrophages stimulated with S. epidermidis.
Peritoneal macrophages isolated from CAPD patients phagocytosed S. epidermidis in a time dependent manner. Coincident with a maximum phagocytic uptake of 56% by 12 hours, there was secretion of a significant amount of neutral protease (1.37 +/- 0.2 mg [3H]-casein degraded/10(6) cells, P = 0.05). In contrast to these delayed effects, coincubation of PMO with S. epidermidis resulted in a significant increase in both LTB4 and LTC4 synthesis above that of controls, with 6.33 +/- 1.20 ng LTB4/10(6) cells (P less than 0.01) and 2.06 +/- 0.68 ng LTC4/10(6) cells (P = 0.014) being generated by three hours. The generation of these lipoxygenase products was both time and dose dependent, and the rapid production and release of the potently chemotactic LTB4 is consistent with the observed clinical response, where a rapid influx of PMN into the peritoneal cavity occurs during episodes of peritonitis, while the generation of LTC4 may contribute to the hyperemia and interstitial edema. In contrast, although there was a time dependent rise in cyclooxygenase product generation by unstimulated cells, a dose dependent inhibition of synthesis was clearly demonstrated when cells were incubated with bacteria, with a mean 40% reduction in generation of PGE2 and a mean 34% reduction in TXB2 generation (P = 0.01 and P less than 0.025, respectively). It was demonstrated that the inhibition was not due to lack of available substrate and that the generation of eicosanoids was unrelated to phagocytosis, bacterial/PMO contact or bacterial surface characteristics. Instead, the observed effect of S. epidermidis on the PMO was attributable to a secreted bacterial product.


Recovery of acetic acid from pre-hydrolysis liquor of hardwood kraft-based dissolving pulp production process by reactive extraction with triisooctylamine.
Acetic acid was one of the main compositions of the pre-hydrolysis liquor (PHL), which was recovered by reactive extraction with triisooctylamine (TIOA) diluted with decanol. Dilution of TIOA played an important role in extracting acetic acid from the PHL. The recovery of acetic acid from the PHL by TIOA was increased from 10.34% to 66.60% with the dilution of TIOA to 20% by decanol at the HAc to TIOA molar ratio of 1, consequently, the equilibrium distribution coefficient KD increased. The effects of time, temperature and pH on the extraction process were also studied. The extraction process was very fast. The acetic acid extraction decreased from 65.13% to 57.34% with the rise of temperature to 50°C from 20°C. A higher pH increased the dissociation of acetic acid, as a result, decreased acetic acid extraction. The hemicelluloses in the PHL were unaffected on the extraction process of acetic acid.


IgM paraproteins with immunological specificity for a Schwann cell component and peripheral nerve myelin in patients with polyneuropathy.
The sera of 9 patients with benign IgM paraproteinaemia and chronic sensorimotor neuropathy were tested for reactivity to human peripheral nerves by the indirect immunoperoxidase method. They reacted in very high titre (10(-3)-10(-6) with a cytoplasmic Schwann cell component, and to lesser degree, with peripheral nerve myelin (10(0)-10(-3). The Schwann cell staining was in the form of perinuclear cytoplasmic granules and was only seen with adult nerve. The distribution of the antigen was similar to that of the metachromatically staining Pi-granules of Reich, which accumulate in the peripheral nerves with age. Specific activity was present in the IgM and F(ab)2 fractions and could be absorbed out with peripheral nerve tissue, but not with liver. Reactivity is not a simple function of the IgM level, since many IgM paraproteins do not react. The antibody is species specific and binds to human, but not to any component of rabbit, rat or guinea pig sciatic nerves. Antigenicity is removed by pretreatment of the nerve with chloroform-methanol or periodate, but not protease or trypsin. Reactivity is restored, after periodate treatment, by exposure to sodium borohydride. It is suggested that some IgM paraproteins have a specificity for a myelin glycolipid or glycoprotein, which normally accumulates in the Pi-granules of the Schwann cell cytoplasm as a function of age.


Approximation of delays in biochemical systems.
In the past metabolic pathway analyses have mostly ignored the effects of time delays that may be due to processes that are slower than biochemical reactions, such as transcription, translation, translocation, and transport. We show within the framework of biochemical systems theory (BST) that delay processes can be approximated accurately by augmenting the original variables and non-linear differential equations with auxiliary variables that are defined through a system of linear ordinary differential equations. These equations are naturally embedded in the structure of S-systems and generalized mass action systems within BST and can be interpreted as linear signaling pathways or cascades. We demonstrate the approximation method with the simplest generic modules, namely single delayed steps with and without feedback inhibition. These steps are representative though, because they are easily incorporated into larger systems. We show that the dynamics of the approximated systems reflects that of the original delay systems well, as long as the systems do not operate in very close vicinity of threshold values where the systems lose stability. The accuracy of approximation furthermore depends on the selected number of auxiliary variables. In the most relevant situations where the systems operate at states away from their critical thresholds, even a few auxiliary variables lead to satisfactory approximations.


Chronic unpredictable stress causes attenuation of serotonin responses in cornu ammonis 1 pyramidal neurons.
In the present study, serotonin (5-HT) responses of hippocampal pyramidal cornu ammonis 1 (CA1) neurons were studied in rats subjected twice daily for 21 days to unpredictable stressors. In hippocampal tissue from thus stressed rats mRNA expression of the 5-HT(1A) receptor and mineralo- as well as glucocorticoid receptors were examined with in situ hybridization. On average, stressed rats displayed increased adrenal weight and attenuated body weight gain compared with controls, supporting that the animals had experienced increased corticosterone levels due to the stress exposure. One day after the last stressor, under conditions that corticosterone levels were low (predominant mineralocorticoid receptor activation), the 5-HT(1A) receptor mediated hyperpolarization of CA1 neurons in response to 10 microM 5-HT was significantly reduced compared with controls. Basal membrane properties of CA1 cells in stressed rats were comparable to those of controls. The 5-HT(1A) receptor mRNA expression was not changed after chronic stress exposure, in any of the hippocampal areas. A small but significant increase in mineralocorticoid receptor mRNA expression was observed after stress in the dentate gyrus, while glucocorticoid receptor expression was unchanged. The data indicate that unpredictable stress exposure for 3 weeks results in suppression of 5-HT(1A) receptor-mediated responses, possibly due to posttranslational modification of the receptor.


Physical activity and physical function improved following a community-based intervention in older adults in Georgia senior centers.
We evaluated a community-based physical activity intervention in Georgia senior centers. Participants were a convenience sample that completed the pre-test only (n = 592), or the pre-test, the intervention, and a post-test (n = 418, 98% aged 60 and older, mean age = 75, 83% female, 56% black). The 4-month physical activity intervention, based on the Health Belief Model, included 16 sessions that focused on educator-led chair exercises, promotion of walking, using a pedometer, and recording daily steps. Pre- and post-tests assessed physical activity and physical function, categorized as poor, moderate, or good (Short Physical Performance Battery). Following the intervention, participants improved their physical function (good physical function at pre-test vs. post-test: 16.5% vs. 25.3%, P < or = 0.001), increased minutes of physical activity by 26% (P < or = 0.001) and step counts by 29% (P < or = 0.0001, sub-sample, n = 95), and decreased reports of "it's not safe" as a barrier to physical activity (P < or = 0.05). Increased physical activity (P < or = 0.01) was associated with improved physical function following the intervention. The results of this evaluation provide an evidence base for the effectiveness of this community intervention for improving physical activity and physical function in older adults.


Incomplete Kawasaki disease in patients younger than 1 year of age: a possible inherent risk factor.
Kawasaki disease (KD) patients younger than 1 year of age are at especially high risk of developing coronary artery abnormalities (CAA). To define the clinical characteristics of this group, as well as the risk factors predisposing them to CAA, we reviewed the medical records of 136 KD patients younger than 1 year of age who were treated at the Korea University Medical Center from January 2001 to July 2006. Of these patients, 16 developed CAA (11.8%). The CAA(+) group had a longer duration of total fever than the CAA(-) group (9.1+/-3.7 days vs. 6.3+/-2.0 days, p=0.011), but did not differ in the duration of pre- and post-intravenous gamma-globulin (IVGG) fever. The CAA(+) group had fewer diagnostic symptoms than the CAA(-) group (2.7+/-1.1 vs. 4.3+/-1.2, p<0.001). Of the hematological findings, the CAA(+) group only differed from the CAA(-) group in having significantly higher total white blood cell (19.2+/-6.0 vs. 14.7+/-4.7 K/mm(3), p=0.007) and platelet (462.9+/-101.0 vs. 383.6+/-121.1 K/mm(3), p=0.014) levels. Multivariable logistic regression analysis showed that the only factors which were significantly associated with the development of CAA were the total number of symptoms (OR=0.493, 95% CI=0.293-0.829, p=0.007) and the duration of total fever (OR=1.405, 95% CI=1.092-1.808, p=0.008). Conclusively, incomplete clinical manifestations and a longer duration of total fever are significantly associated with the development of CAA in KD patients younger than 1 year of age. Therefore, these patients should be monitored for incomplete KD, especially if unexplained fever continues, and treatment to shorten the duration of total fever should be initiated.


Adaptation to tilting of the visual environment in cyclotropia.
We evaluated adaptations to tilting of the visual environment in 18 patients with cyclotropia by comparison of subjective tests for torsion with the actual rotation of the globes determined by fundus photography. Patients with congenital cyclotropia had a sensory reorientation of the spatial values of retinal meridians in the cyclotropic eye that prevented awareness of tilting of the environment under uniocular and binocular conditions. Patients with cyclotropia acquired as adults in many instances also had retinal sensory reorientations of the cyclotropic eye or eyes. Additionally, they used spatial clues from the visual environment to correct for image tilting under uniocular conditions. Under dissociated binocular conditions, however, these patients became aware of tilting of the visual environment, and therefore these adaptations were less deeply rooted than those in patients with congenital cyclotropia. Because certain patients with acquired cyclotropia showed evidence of using these adaptations under uniocular conditions but had constant or intermittent torsional diplopia under casual binocular viewing conditions, binocular mechanisms such as cyclofusion, suppression, and anomalous retinal correspondence may also be necessary to eliminate subjective tilting of the visual environment.


Identification of diagnostic signatures in ulcerative colitis patients via bioinformatic analysis integrated with machine learning.
Ulcerative colitis (UC) is an immune-related disorder with enhanced prevalence globally. Early diagnosis is critical for the effective treatment of UC. However, it still lacks specific diagnostic signatures. The aim of our study was to explore efficient signatures and construct the diagnostic model for UC. Microarray data of GSE87473 and GSE48634, which were obtained from tissue biopsy samples, were downloaded from the Gene Expression Omnibus (GEO), and differently expressed genes (DEGs), GO, and KEGG analyses were performed. We constructed the PPI network via STRING database. The immune infiltration of the samples was evaluated using CIBERSORT methods combined with the LM22 feature matrix. The logistic regression model was constructed, with the expression of selected genes as the predictor variable, and the UC occurrence as the responsive variable. As a result, a total of 126 DEGs between the UC patients and normal counterparts were identified. The GO and KEGG analysis revealed that multiple biological processes, such as antimicrobial humoral immune response mediated by antimicrobial peptide and IL-17 signaling pathway, were enriched. The infiltration of eight immune cell types (B cells naive, Dendritic.cells.activated, Macrophages.M0, Macrophages.M2, Mast.cells.resting, Neutrophils, Plasma.cells, and T.cells.follicular.helper) was significantly different between patients with UC and normal counterparts. The top 50 most significant DEGs were selected for the construction of the PPI network. The average AUC of the logistic regression model in the fivefold cross-validation was 0.8497 in the training set, GSE87473. The AUC of another independent verification set of GSE48634 from the GEO database was 0.7208. In conclusion, we identified potential hub genes, including REG3A, REG1A, DEFA6, REG1B, and DEFA5, which might be significantly associated with UC progression. The logistic regression model based on the five genes could reliably diagnose UC patients.


A study of the lagged relationships among safety climate, safety motivation, safety behavior, and accidents at the individual and group levels.
The authors measured perceptions of safety climate, motivation, and behavior at 2 time points and linked them to prior and subsequent levels of accidents over a 5-year period. A series of analyses examined the effects of top-down and bottom-up processes operating simultaneously over time. In terms of top-down effects, average levels of safety climate within groups at 1 point in time predicted subsequent changes in individual safety motivation. Individual safety motivation, in turn, was associated with subsequent changes in self-reported safety behavior. In terms of bottom-up effects, improvements in the average level of safety behavior within groups were associated with a subsequent reduction in accidents at the group level. The results contribute to an understanding of the factors influencing workplace safety and the levels and lags at which these effects operate.


(18)F-labelled cardiac PET tracers: selected probes for the molecular imaging of transporters, receptors and proteases.
Designated radiopharmaceuticals labelled with the prominent positron-emitter (18)F can be defined as molecular imaging probes for the examination of cardiovascular diseases at the cellular and subcellular level. Such molecular imaging agents representing radioindicators or radiotracers offer the opportunity to non-invasively trace their path and fate in the living organism by the scintigraphic technique, positron emission tomography (PET). The glucose analogue [(18)F]FDG is a widespread PET tracer and one of the earliest examples of a PET molecular imaging probe feasible to in vivo visualise glucose utilisation by a metabolic trapping mechanism. This short review is focussed on selected established (18)F-labelled PET tracers as well as (18)F-labelled radioligands in development that show the potential of being probes for the in vivo molecular imaging of proteins relevant in cardiovascular diseases such as receptors (i.e. beta-Adrenoceptors), transporters (i.e. NET and VMAT) and proteases (i.e. MMPs).