Transcriptome analysis of hepatic gene expression and DNA methylation in methionine- and betaine-supplemented geese (Anser cygnoides domesticus).
Dietary methionine (Met) restriction produces a coordinated series of transcriptional responses in the liver that limits growth performance and amino acid metabolism. Methyl donor supplementation with betaine (Bet) may protect against this disturbance and affect the molecular basis of gene regulation. However, a lack of genetic information remains an obstacle to understand the mechanisms underlying the relationship between Met and Bet supplementation and its effects on genetic mechanisms. The goal of this study was to identify the effects of dietary supplementation of Met and Bet on growth performance, transcriptomic gene expression, and epigenetic mechanisms in geese on a Met-deficient diet. One hundred and fifty 21-day-old healthy male Yangzhou geese of similar body weight were randomly distributed into 3 groups with 5 replicates per treatment and 10 geese per replicate: Met-deficient diet (Control), Control+1.2 g/kg of Met (Met), and Control+0.6 g/kg of Bet (Bet). All geese had free access to the diet and water throughout rearing. Our results indicated that supplementation of 1.2 g/kg of Met in Met-deficient feed increased growth performance and plasma homocysteine (HCY) levels, indicating increased transsulfuration flux in the liver. Supplementation of 0.6 g/kg Bet had no apparent sparing effect on Met needs for growth performance in growing geese. The expression of many genes critical for Met metabolism is increased in Met supplementation group. In the Bet-supplemented group, genes involved in energy production and conversion were up-regulated. Dietary supplementation with Bet and Met also altered DNA methylation. We observed changes in the methylation of the LOC106032502 promoter and corresponding changes in mRNA expression. In conclusion, Met and Bet supplementation in geese affects the transcriptional regulatory network and alters the hepatic DNA methylation of LOC106032502.


In vitro protective effects of Withania somnifera (L.) dunal root extract against hydrogen peroxide and β-amyloid(1-42)-induced cytotoxicity in differentiated PC12 cells.
Withania somnifera L. Dunal (Solanaceae), also known as 'ashwagandha' in Sanskrit and as 'Indian ginseng', is used widely in Ayurvedic medicine as a nerve tonic and memory enhancer, with antiaging, antistress, immunomodulatory and antioxidant properties. There is a paucity of data on the potential neuroprotective effects of W. somnifera root, as traditionally used, against H(2)O(2)- and Aβ((1-42))-induced cytotoxicity which are current targets for novel approaches to treat dementia, especially dementia of the Alzheimer's type (AD). In this study, an aqueous extract prepared from the dried roots of W. somnifera was assessed for potential protective effects against H(2)O(2)- and Aβ((1-42))-aggregated fibril cytotoxicity by an MTT assay using a differentiated rat pheochromocytoma PC12 cell line. The results suggest that pretreatments of differentiated PC12 cells with aqueous extracts of W. somnifera root significantly protect differentiated PC12 cells against both H(2)O(2)- and Aβ((1-42))-induced cytotoxicity, in a concentration dependent manner. To investigate the compounds that could explain the observed effects, the W. somnifera extract was analysed by liquid chromatography-serial mass spectrometry and numerous withanolide derivatives, including withaferin A, were detected. These results demonstrate the neuroprotective properties of an aqueous extract of W. somnifera root and may provide some explanation for the putative ethnopharmacological uses of W. somnifera for cognitive and other neurodegenerative disorders that are associated with oxidative stress.


Electron paramagnetic resonance studies of functionally active, nitroxide spin-labeled peptide analogues of the C-terminus of a G-protein alpha subunit.
The C-terminal tail of the transducin alpha subunit, Gtalpha(340-350), is known to bind and stabilize the active conformation of rhodopsin upon photoactivation (R*). Five spin-labeled analogues of Gtalpha(340-350) demonstrated native-like activity in their ability to bind and stabilize R*. The spin-label 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid (TOAC) was employed at interior sites within the peptide, whereas a Proxyl (3-carboxyl-2,2,5,5-tetramethyl-pyrrolidinyloxy) spin-label was employed at the amino terminus of the peptide. Upon binding to R*, the electron paramagnetic resonance spectrum of TOAC(343)-Gtalpha(340-350) revealed greater immobilization of the nitroxide when compared to that of the N-terminally modified Proxyl-Gtalpha(340-350) analogue. A doubly labeled Proxyl/TOAC(348)-Gtalpha(340-350) was examined by DEER spectrocopy to determine the distribution of distances between the two nitroxides in the peptides when in solution and when bound to R*. TOAC and Proxyl spin-labels in this GPCR-G-protein alpha-peptide system provide unique biophysical probes that can be used to explore the structure and conformational changes at the rhodopsin-G-protein interface.


Postoperative imaging of the aorta.
Considerable progress has been made in the management of diseases of the thoracic and abdominal aorta over the past decades, ranging from advances in open repair to the advent of minimally invasive endovascular techniques. Along with this comes an equivalent rise in imaging necessity for these patients, both in preoperative planning and postoperative surveillance. With the growing complexity and diversity of vascular procedures and techniques, it is essential to have a solid understanding of the imaging features and postoperative complications of these procedures to avoid imaging pitfalls. This review is an attempt to define the normal postoperative appearance and important complications of various open and endovascular surgical techniques of the thoracic and abdominal aorta.


Spatiotemporal focusing dynamics of intense supercontinuum THz pulses.
High-field terahertz (THz) single-cycle pulses with 1.5 MV/cm are generated by optical rectification in the stilbazolium salt crystal 4-N,N-dimethylamino-4'-N'-methyl-stilbazolium 2,4,6-trimethylbenzenesulfonate. We show experimentally that the generated THz transient carrying 5 octaves (0.15 to 5.5 THz) undergoes a complex time-frequency evolution when tightly focused, and we present a model based on three independent oscillating dipoles capable to describe this anomalous field evolution. Finally, we present a method to control the absolute phase of such supercontinuum THz pulses as an essential tool for future field-sensitive investigations.


Reconciling employment with caring for a husband with an advanced illness.
Little is known about combining work with caring for a person with advanced illness. This is important given the increasing number of women in the workforce and current policy seeking to increase care in the community. The aim of this paper was to explore the meaning of work for women caring for a husband with an advanced illness and the consequences of combining these two roles. A purposive sample of 15 carers was recruited from a hospital and from the community, via the patients they cared for. Their illnesses included chronic obstructive pulmonary disease, cancer, motor neurone disease, and heart failure. Data were collected through semi-structured, in-depth interviews that were tape-recorded and transcribed verbatim. A Grounded Theory approach was used and case studies were developed. NVivo software facilitated the management and analysis of the data. Caring presented challenges to carers' work life. It diminished productivity or the quality of work, and led to missed opportunities for promotion. Work had an effect on the quality of care and the relationship with the patient, which eventually led to work being given up for caring. Three carers resisted the pressures to give up work and used it as a coping strategy. A positive choice to remain in employment does not necessarily signal reluctance to care. Caring arrangements need to be understood from the common and separate interests of carers and the people they support.


Effect of a novel PACAP-27 analogue on muscarinic airway responsiveness in guinea-pigs in vivo.
A recent study showed that the novel pituitary adenylate cyclase-activating peptide (PACAP)-27 analogue [Arg15,20,21,Leu17]-PACAP-27-Gly-Lys-Arg-NH2 causes sustained airway smooth muscle relaxation in vitro. This study examined whether this analogue also has bronchoprotective effects, by inhibiting muscarinic airway responsiveness in vivo. Total lung resistance was measured in anaesthetized, tracheostomized and ventilated guinea-pigs. Increasing doses of acetylcholine were given i.v. once before and thereafter repeatedly each hour after intratracheal instillation of either the PACAP-27 analogue or the clinical beta2-agonist bronchodilator salbutamol. Mean arterial blood pressure (MAP) was monitored to detect cardiovascular side-effects. Both the PACAP-27 analogue and salbutamol significantly attenuated the airway responsiveness to acetylcholine. The total inhibitory effect of the PACAP-27 analogue (350 nmol) corresponded to that of salbutamol (35 nmol). The inhibitory effect of salbutamol (35 nmol) peaked during the second hour and disappeared prior to 5 h after administration. In contrast, the corresponding effect of the analogue (350 nmol) gradually increased and peaked during the fifth hour after administration, whereas it did not fade during the observation period. Both the PACAP-27 analogue (350 nmol) and salbutamol (35 nmol) produced a transient decrease in MAP within 6 min after administration. In conclusion, the novel pituitary adenylate cyclase-activating peptide-27 analogue has bronchoprotective properties, by decreasing muscarinic airway responsiveness in guinea pigs in vivo. The time course of its effect is compatible with a more sustained duration of action compared with salbutamol.


Comparison of tidal volumes, minute ventilation, and respiratory frequencies delivered by paramedic and respiratory care students with pocket mask versus demand valve.
The importance of establishing the airway and providing ventilation during resuscitation is well recognized; however, the effectiveness of demand-valve ventilation has not been fully addressed. We examined the differences in respiratory frequency (f), tidal volume (VT), and minute ventilation (VE) achieved by 15 emergency medical technicians (EMT) in a paramedic training course (EMT-4) and 16 second-year respiratory care students (RC) when ventilating a mannequin by three different methods: Laerdal pocket mask, a mask designed for mouth-to-mask ventilation (Method I), demand valve with one hand (Method II), and demand valve with two hands (Method III). The RC f was much higher for all three methods compared to the EMT-4. The EMT-4 demonstrated larger VT for each method compared to the RC. The RC only achieved acceptable VT with Method III. The EMT-4 and RC demonstrated statistically significant differences in VE between each method. However, the clinical importance of these differences for EMT-4 is negligible. Although the mean values indicated achievement of minimum VTS by the EMT-4 with the pocket mask, 40% were unable to do so at 1 minute and 60% at 5 minutes. A great difference was seen in VE produced by RC with Method I at both 1 and 5 minutes vs Methods II and III. EMT-4 appear to have superior ventilation skills compared to RC. Superior performance skills may be related to (1) different instructional methodologies, (2) effects of various amounts of experience in ventilating actual victims, and (3) greater familiarity of EMTs with the demand valve. As a consequence of this study, we are re-evaluating the instructional methodology used in our programs; we encourage other programs to do the same. We recommend that EMS providers and hospitals consider changing to an acceptable alternate mask in light of these and previous data.


Asthma increase among farmers: a 12-year follow-up.
Respiratory disease is a well known health hazard for farmers, but the long-term prognosis is less well known. This is a 12-year follow-up of an investigation of Swedish farmers, most of them dairy farmers. A questionnaire was mailed to all 418 farmers who were alive of the farmers originally participating in 1982. They were invited to an interview, spirometry, and blood sampling. Ninety-one per cent (380) of the farmers, 321 men and 59 women, responded to the questionnaire. The mean age was 56 years for the men and 55 years for the women. Of the group, 10% were smokers, 25% ex-smokers, and 65% had never smoked. The population estimate for asthma in the farmers was 8.9% in 1994 compared to 2% in 1982, and to 5.4%-6.6% in the general population in the region in 1982. Of the asthmatic subjects, one-third had positive RAST tests (radioallergosorbent tests). Almost 90% of the new onset asthma cases since 1982 had non-IgE-mediated asthma. Most of the IgE-mediated asthmatics had had symptoms for many years, while 70% of the non-IgE-mediated asthmatic farmers had no or only wheezing with colds 1982. Two new cases of hypersensitivity pneumonitis were identified, and 7.3% had experienced inhalation fever during the last 12 years. In general, individuals with asthma and chronic bronchitis who had left farming were in better health in 1994 as compared to 1982. In conclusion, farmers have an enhanced risk to develop asthma increasing with age. Asthma in farmers is often non-IgE-mediated.


Modulation of SR Ca release by luminal Ca and calsequestrin in cardiac myocytes: effects of CASQ2 mutations linked to sudden cardiac death.
Cardiac calsequestrin (CASQ2) is an intrasarcoplasmic reticulum (SR) low-affinity Ca-binding protein, with mutations that are associated with catecholamine-induced polymorphic ventricular tachycardia (CPVT). To better understand how CASQ2 mutants cause CPVT, we expressed two CPVT-linked CASQ2 mutants, a truncated protein (at G112+5X, CASQ2(DEL)) or CASQ2 containing a point mutation (CASQ2(R33Q)), in canine ventricular myocytes and assessed their effects on Ca handling. We also measured CASQ2-CASQ2 variant interactions using fluorescence resonance transfer in a heterologous expression system, and evaluated CASQ2 interaction with triadin. We found that expression of CASQ2(DEL) or CASQ2(R33Q) altered myocyte Ca signaling through two different mechanisms. Overexpressing CASQ2(DEL) disrupted the CASQ2 polymerization required for high capacity Ca binding, whereas CASQ2(R33Q) compromised the ability of CASQ2 to control ryanodine receptor (RyR2) channel activity. Despite profound differences in SR Ca buffering strengths, local Ca release terminated at the same free luminal [Ca] in control cells, cells overexpressing wild-type CASQ2 and CASQ2(DEL)-expressing myocytes, suggesting that a decline in [Ca](SR) is a signal for RyR2 closure. Importantly, disrupting interactions between the RyR2 channel and CASQ2 by expressing CASQ2(R33Q) markedly lowered the [Ca](SR) threshold for Ca release termination. We conclude that CASQ2 in the SR determines the magnitude and duration of Ca release from each SR terminal by providing both a local source of releasable Ca and by effects on luminal Ca-dependent RyR2 gating. Furthermore, two CPVT-inducing CASQ2 mutations, which cause mechanistically different defects in CASQ2 and RyR2 function, lead to increased diastolic SR Ca release events and exhibit a similar CPVT disease phenotype.


[Comparative histological and cytological characteristics of peripheral lung cancer].
Peripheral pulmonary carcinoma was analysed retrospectively histologically, histochemically, and cytologically. The examination material (smears taken at percutaneous thoracic aspirational biopsy, resected lung or lung lobe) had been obtained from 113 patients with PPC among whom 85 patients underwent pulmon- or lobe-ectomy. Cytological examination of specimens from percutaneous thoracic biopsy allowed the diagnosis of PPC to be established in 90.6% of cases and to determine correctly the histological type of cancer in 85.7%. No regular correlation between the levels of tissue and cellular differentiation in squamous cell carcinoma and adenocarcinoma was found. Argyrophilic granules (Grimelius reaction) were detected in cells of combined oat cell carcinoma and small cell carcinoma of transitional type. Because of the existence of combined tumors in the lungs consisting of cells of different types of differentiation it is suggested that complex histological types of pulmonary carcinoma can develop from a common polypotent precursor cell.


Repeated oestrus synchrony and fixed-time artificial insemination in beef cows.
The feasibility of breeding spring-calving, single-suckled beef cows without the use of natural service was investigated over two breeding seasons by using repeated oestrus synchrony and fixed-time artificial insemination (AI). Initially, cows were oestrus-synchronised with subcutaneous norgestomet implants inserted for 10 days, with an injection of prostaglandin before the implants were removed. The cows were inseminated once 56 hours after the implants were removed, and 12 days later they were re-treated with norgestomet implants to allow a second synchronised service. Twenty-one days after the first synchronised AI, milk samples were taken for progesterone assay and the norgestomet implants were removed. The cows received a second service 56 hours later if the 21-day milk progesterone assay suggested that they were not pregnant. All the cows receiving a second service were retreated with norgestomet implants to allow a third synchronised service as necessary. Pregnancy was later confirmed by rectal palpation. In the first year, 48 cows entered the programme and the pregnancy rates to the first, second and third synchronised services were 56, 69 and 40 per cent, respectively, with 17 per cent of cows barren at the end of the breeding period. In the second year, 69 cows entered the programme and the pregnancy rates were 58, 48 and 33 per cent to the successive services with 20 per cent of cows barren at the end of the breeding period. The accuracy of milk progesterone assay for pregnancy diagnosis was 84 per cent and 87 per cent in the first and second years, respectively.


Oligosaccharides in infant formula.
Breast-feeding is the golden standard for infant feeding. However, the majority of a few week old infants are fed with a second choice infant feeding, cow's milk based formula. Amongst the multiple differences between human and cow's milk regards the development of the gastro-intestinal flora: the flora of the breast-fed infant being richer in bifidobacteria and lactobacilli. Both species are known to be potentially beneficial for the health of the host. The absence of oligosaccharides, the third largest component in human milk, in cow's milk is likely to account for the differences in colonic flora. The oligosaccharide content and concentration in breast milk is - just as for the other macronutrients - a dynamic process, making it impossible for industry to mimic nature. However, if the composition cannot be mimicked, the effect and function can be imitated. The addition of two oligosaccharides, galacto-oligosaccharides and inulin, to cow's milk based infant formula has been shown to have a bifidogenic effect, and to stimulate the growth of bifidi and lactobacilli. In conclusion, the addition of oligosaccharides to cow's milk based infant formula brings this alternative, second choice infant feeding one step closer to the golden standard of human milk. But, prolonged breast-feeding should still be promoted with maximum effort.


Delivering regional thrombolysis via a hub-and-spoke model.
Audits in the United Kingdom and other countries show that only a small proportion of eligible stroke patients receive thrombolysis. Providing 24-hour thrombolysis cover presents major challenges in both infrastructure and staffing. One model for improving access is to provide out-of-hours cover in a regional centre but this may present problems including greater delays to hospital admissions. Evaluation of the introduction of a 'hub-and-spoke' model of thrombolysis to increase access to thrombolysis for patients in south west London. One-year data are presented. A network in south-west London comprised of a hub hospital and three district 'spoke' hospitals. All suspected stroke admissions to a regional stroke centre. Main outcome measures Thrombolysis rates for acute stroke. Increased out-of-hours thrombolysis rates were achieved with only a small increase in stroke admissions (approximately 10%) in the hub hospital. Thrombolysis rates increased from 1.2 per 100 stroke admissions for the local daytime service to 6 per 100 admissions for the regional service. Most patients thrombolysed were not local to the hub hospital. Only 1 in 4 patients considered for thrombolysis was thrombolysed, in line with previous data. Ten percent of all thrombolysis calls were not stroke but represented stroke mimics. Median length of stay was 6 days (target was 3 days). Fifty percent of the thrombolysed patients from spoke hospitals were discharged directly home. In an urban area, a hub-and-spoke thrombolysis model increased access to thrombolysis without resulting in a marked increase in overall stroke admission numbers for the hub hospital. Proactive plans to repatriate patients back to district hospitals are required, and repatriation protocols have to prioritize regional patients over other targets in spoke hospitals to facilitate capacity in the hub hospital.


The efficacy of intravesical bacillus Calmette-Guerin in the treatment of patients with pT1 stage non-muscle-invasive bladder cancer.
pT1 bladder urothelial carcinomas represent a heterogeneous group of tumors with different biologic behaviors, and identifying the subset of tumors that carries a high risk of disease recurrence and progression is therefore important. Induction and maintenance intravesical Bacillus Calmette-Guerin (BCG) has been proven to reduce tumour recurrence and progression. However, no markers are available to predict BCG response. The aim of this study is to evaluate the prognostic factors of stage in predicting recurrence after intravesical adjuvant BCG immunotherapy in patients with NMIBC. we retrospectively reviewed the clinical and pathologic data of primary NMIBC from 45 patients who were treated with transurethral resection followed by BCG-immunotherapy. Time follow-up was 30 months. The prognostic significance of clinicopathologics characteristics in determining the risk for recurrence after BCG therapy was studied with both univariate and multivariate methods of analysis. univariate Cox regression analysis of clinicopathologic characteristics revealed that the rate of recurrence was statistically associated with tumor stage. Indeed, a significant concordance was noted between the EORTC s predicted risks and the actuarial recurrence rate of NMIBC at one year. On the other hand, multivariate analysis using Cox regression based on the AIC criteria and biological considerations, selected the score of recurrence as independent predictor of recurrence. The conventional clinicopathological factors used in EORTC model are relevant for the assessment of the outcome of pT1 stage bladder tumors treated by BCG immunotherapy. Management of pT1 bladder cancer patients remains one of the most difficult problems in urologic practice. At this time the decision to preserve the bladder or to perform a cystectomy depends on a number of clinicopathologic parameters, but none are able to sufficiently identify patients for the appropriate therapeutic modality. Additional studies using a more large scale of patients will be required to confirm our findings.


Effect of Yoga or Physical Exercise on Muscle Function in Rural Indian Children: A Randomized Controlled Trial.
Synergistic effects of yoga or physical exercise (PE) along with protein supplementation on children's muscle function in rural India have not been studied. Hence, we aimed to study the effect of yoga and PE along with protein supplementation on muscle function in healthy 6- to 11-year-old rural Indian children post 6 months of intervention. A randomized controlled trial on 232 children, recruited into 3 groups, each receiving 1 protein-rich ladoo (148 kcal, 7 g protein/40 g ladoo-an Indian sweet snack) daily and performing (1) yoga (n = 78) for 30 minutes 5 times per week, (2) PE (n = 76) for 30 minutes 5 times per week, or (3) control group (n = 78) no additional exercise. Maximum power, maximum voluntary force (Fmax), and grip strength (GS) were measured. Data were analyzed using paired t tests and a 2-way mixed analysis of variance with post hoc Bonferroni adjustment. GS, maximum power, and Fmax within yoga group increased significantly (P < .05) from baseline to endline. GS and Fmax increased significantly within PE group postintervention (P < .001). In controls, GS increased (P < .05) at endline. No significant effect of the intervention was observed on the change in maximum power (P > .05) postintervention. The 2 exercise groups showed significant increase in Fmax compared with the control group (P < .05). Similarly, increase in GS was significantly higher in both the exercise groups compared with the control group (P < .05). No significant difference was observed in change in muscle function between the 2 exercise groups (P > .05). Structured physical activity along with protein supplementation resulted in improved muscle function in children. Yoga and PE showed a comparable impact on muscle force.


Reversing dabigatran in life-threatening bleeding occurring during cardiac ablation with factor eight inhibitor bypassing activity.
We report a case of a patient receiving dabigatran who developed a life-threatening bleeding complication during cardiac ablation that rapidly resolved after administration of Factor Eight Inhibitor Bypassing Activity (FEIBA). Therapeutic anticoagulation with warfarin during cardiac ablation has been shown to reduce the risk of stroke and systemic embolism. Cardiac tamponade is a potentially life-threatening procedural complication requiring emergent reversal of anticoagulation and pericardiocentesis. Dabigatran is superior to warfarin in preventing stroke and systemic embolism in nonvalvular atrial fibrillation, but has not been evaluated for use during cardiac ablation. Dabigatran is without a known reversal agent and, should tamponade occur during ablation, it is unclear what reversal strategy could be used to establish hemostasis. A 67-year-old man with history of atrial fibrillation with rapid ventricular rate, two previous atrial fibrillation ablations, and prescribed dabigatran 150 mg bid was admitted for an atrial fibrillation ablation procedure. The last dabigatran dose was 7 hours prior to procedure. During the procedure, a transseptal perforation occurred, requiring an emergent pericardiocentesis. Within 60 minutes, approximately 4.5 L of blood was removed via the pericardiocentesis. Low-dose FEIBA (3159 units, 26 U/kg actual body weight) over 15 minutes was administered. Hemostasis was noted within minutes of initiating the infusion with cessation of bleeding after administration was complete. This case report describes the potential ability of a low dose of the activated prothrombin complex concentrate, FEIBA, to reestablish hemostasis independent of the pharmacologic effects of dabigatran. Additional studies are warranted to confirm the findings of our observation.


Effects of individual health topic familiarity on activity patterns during health information searches.
Non-medical professionals (consumers) are increasingly using the Internet to support their health information needs. However, the cognitive effort required to perform health information searches is affected by the consumer's familiarity with health topics. Consumers may have different levels of familiarity with individual health topics. This variation in familiarity may cause misunderstandings because the information presented by search engines may not be understood correctly by the consumers. As a first step toward the improvement of the health information search process, we aimed to examine the effects of health topic familiarity on health information search behaviors by identifying the common search activity patterns exhibited by groups of consumers with different levels of familiarity. Each participant completed a health terminology familiarity questionnaire and health information search tasks. The responses to the familiarity questionnaire were used to grade the familiarity of participants with predefined health topics. The search task data were transcribed into a sequence of search activities using a coding scheme. A computational model was constructed from the sequence data using a Markov chain model to identify the common search patterns in each familiarity group. Forty participants were classified into L1 (not familiar), L2 (somewhat familiar), and L3 (familiar) groups based on their questionnaire responses. They had different levels of familiarity with four health topics. The video data obtained from all of the participants were transcribed into 4595 search activities (mean 28.7, SD 23.27 per session). The most frequent search activities and transitions in all the familiarity groups were related to evaluations of the relevancy of selected web pages in the retrieval results. However, the next most frequent transitions differed in each group and a chi-squared test confirmed this finding (P<.001). Next, according to the results of a perplexity evaluation, the health information search patterns were best represented as a 5-gram sequence pattern. The most common patterns in group L1 were frequent query modifications, with relatively low search efficiency, and accessing and evaluating selected results from a health website. Group L2 performed frequent query modifications, but with better search efficiency, and accessed and evaluated selected results from a health website. Finally, the members of group L3 successfully discovered relevant results from the first query submission, performed verification by accessing several health websites after they discovered relevant results, and directly accessed consumer health information websites. Familiarity with health topics affects health information search behaviors. Our analysis of state transitions in search activities detected unique behaviors and common search activity patterns in each familiarity group during health information searches.


Identification of enzymes catalyzing two-step phosphorylation of cidofovir and the effect of cytomegalovirus infection on their activities in host cells.
Cidofovir [CDV; (S)-1-(3-hydroxy-2-phosphonomethoxyethyl)cytosine] is an acyclic nucleotide analog with potent and selective in vitro and in vivo activities against a broad spectrum of herpesviruses and other DNA viruses. We studied the mechanism of enzymatic synthesis of CDV diphosphate, the putative antiviral metabolite of CDV. The phosphorylation is two-step process catalyzed by several enzymes. An enzymatic activity phosphorylating CDV to its monophosphate derivative was purified from human liver and identified as pyrimidine nucleoside monophosphate kinase (EC 220.127.116.11.). CDV (Km = 2.10 +/- 0.18 mM and Vmax = 1.10 +/- 0.05 micromol/min/mg) was found to be a substantially weaker substrate for purified enzyme than CMP, UMP, or dCMP. Pyrimidine nucleoside monophosphate kinase was used for preparative enzymatic synthesis of CDV monophosphate. Pyruvate kinase (EC 188.8.131.52), creatine kinase (EC 188.8.131.52), and nucleoside diphosphate kinase (EC 220.127.116.11) were found to catalyze CDV diphosphate synthesis from CDV monophosphate, whereas phosphoglycerate kinase (EC 126.96.36.199) and succinyl-CoA synthetase (EC 22.214.171.124) did not. Based on Vmax/Km (phosphorylation efficiency) values determined with enzymes purified from human sources, the most efficient phosphorylation of CDV monophosphate is catalyzed by pyruvate kinase. After infection of human lung fibroblasts with cytomegalovirus, the intracellular activities of pyrimidine nucleoside monophosphate kinase, pyruvate kinase, creatine kinase, and nucleoside diphosphate kinase increased 2-, 1.3-, 3-, and 5-fold, respectively. The metabolism of [3H]CDV in mock- and cytomegalovirus-infected cells was examined. The intracellular levels of CDV monophosphate and CDV diphosphate increased approximately 20- and 8-fold, respectively, in cytomegalovirus-infected cells, presumably due to the stimulation of CDV uptake and higher activities of phosphorylating enzymes.


Multi-microjoule, MHz repetition rate Ti:sapphire ultrafast regenerative amplifier system.
We demonstrate a cryogenically cooled Ti:sapphire ultrafast regenerative amplifier laser system producing >20 μJ energies at 50 kHz, >12 μJ at 200 kHz and >3.5 μJ at 1MHz with repetition rates continuously tunable from 50 kHz up to 1.7 MHz in a footprint of only 60x180 cm². This laser uses down-chirped pulse amplification employing a grism stretcher and a glass-block compressor, achieving sub-60-fs pulse duration. This laser represents a several-times improvement in repetition-rate and average power over past Ti:sapphire-based ultrafast lasers in this class. We discuss the unique challenges and solutions for this laser system. This laser system has wide applications especially in ultrafast photoemission, nonlinear imaging and spectroscopy, as well as for micro/nano-machining and ultrafast laser therapy and surgery.


Influence of Alkalinization Over Metal Organic Frameworks MIL-100(Fe) for Enhanced Volatile Organic Compounds (VOCs) Adsorbents.
Substantial attempts have been undertaken for the improvement of the air quality over decades; and Volatile Organic Compounds (VOCs) from the chemical and textile industries are truly listed as severe issue to be controlled. To come up with modus operandi for this issue, a novel composite of metal organic frameworks (MOFs) MIL-100(Fe) with salient tuned features of natrite was designed by a green and facile method. Mineralized composite MOFs exhibited enhanced crystallinity than pure MIL-100(Fe) as well showcased a higher surface area of 1300 m² g-1. Through dynamic acetone pressure swing adsorption setup, MIL-0.05Na (MIL-100(Fe) synthesized with 0.05 mM Na₂CO₃ solution) revealed an enhanced acetone adsorption of 210 mg g 1 at room temperature. Gas phase adsorption isotherms confirmed the mono layer adsorption behavior. The kinetics models evaluated that the external mass transfer was the rate limiting step for surface adsorption. The thermodynamic study manifested that the adsorption reaction was spontaneous and exothermic. The proposed mechanism of adsorption was the act of physisorption which enriched the adsorbents reusability. This research work provides a futuristic vista to design mineralized Fe-MOFs composites for an energy saving adsorbents for VOCs removal.


Coal and the Present Energy Situation: Abundant coal reserves can be used to alleviate the oil and gas shortage.
To summarize, we must make greater use of coal, an energy resource that the nation has in great abundance, if we are to approach our former position of self-sufficiency in energy production. The first step is to move immediately to replace the oil and gas used in electric generating plants with coal and to require that coal be used in fossil fuel electric plants planned or under construction in the next few years. The technology to remove sulfur and particulates from the stack gases is at hand, and therefore environmental regulations can be met. Producing and transporting the required increased tonnages of coal are problems that can be met with appropriate incentives to the coal and transportation industries. Improved mining technology would be helpful but is not a requiremlent. Oil and gas from coal should be in significant commercial production in about a decade. Underground, or in situ, gasification of coal, now in field tests, looks promising as a practical process for recovering the energy from coal, especially in deep or thick beds that cannot be mined efficiently. Recoverable methane occurs in coal beds in the United States in an amount approximately equal to the total reserves of natural gas-about 260 trillion cubic feet. This large reserve of natural gas should be exploited as quickly as possible. Only minor investments in exploration and modest advances in technology are required. Finally, as coal production is expanded. adequate planning and the most modern technology should be used to ensure that coal is extracted with maximum recovery and with minimum damage to the environment.


The antimicrobial efficacy of a silver alginate dressing against a broad spectrum of clinically relevant wound isolates.
Wound dressings impregnated with silver have a role to play in aiding to reduce both the dressing and wound microbial bioburden. It is therefore imperative that antimicrobial wound dressings have efficacy on a broad range of clinical significant microorganisms. Accordingly, this study aimed to determine the antimicrobial efficacy of a silver alginate dressing against 115 wound isolates that had been isolated routinely from patients at West Virginia University Hospital. Standardised corrected zones of inhibition (CZOIs) were performed on all clinical isolates. It was found that the silver alginate dressing was able to inhibit the growth of all microorganisms tested. In particular, the silver alginate dressing inhibited the growth of Candida albicans and yeasts with CZOI of 3-11·5 mm. All meticillin-resistant Staphylococcus aureus (MRSA) strains were found to be sensitive to the silver alginate dressing with a CZOI range calculated at 3-7·8 mm. Sensitivity to the silver alginate dressing was also evident for S. aureus and vancomycin-resistant Enterococci. CZOIs of 4·25 mm were calculated for Enterococcus faecium and 9·8 mm for viridans streptococcus. The bacteria which demonstrated the highest tolerance to ionic silver included Enterobacter cloacae and Acinetobacter baumannii. Contrary to this the most responsive microorganisms to ionic silver included strains of staphylococci, viridans streptococcus and Candida albicans. No antibiotic-resistant isolates, as identified by Kirby Bauer Clinical Laboratory Standards Institute classification system, were found to be resistant to ionic silver. When a selected number of microorganisms were grown in the biofilm phenotypic state enhanced tolerance to silver was observed, compared to their non biofilm counterparts. Overall, this study has demonstrated the broad antimicrobial activity of a silver alginate dressing on wound isolates grown in the non biofilm and biofilm state. This finding is clinically relevant as both the non biofilm and biofilm phenotypic states of microorganisms are evident in wounds and therefore significant to delayed healing. Consequently, it is imperative that antimicrobial wound dressings demonstrate antimicrobial activity against microorganisms in both phenotypic states.


The dual amylin and calcitonin receptor agonist KBP-089 and the GLP-1 receptor agonist liraglutide act complimentarily on body weight reduction and metabolic profile.
Weight loss therapy is becoming more and more important, and two classes of molecules, namely amylin receptor and GLP-1 receptor agonists, have shown promise in this regard. Interestingly, these molecules have several overlapping pharmacological effects, such as suppression of gastric emptying, reduction of glucagon secretion and weight loss in common; however, they also have distinct effects on prandial insulin secretion. Hence, a combination of these two mechanisms is of significant interest. In this study, we investigated the add-on potential of the dual amylin and calcitonin receptor agonist (DACRA) KBP-089 in combination with the GLP-1 receptor agonist liraglutide as obesity treatment in high-fat diet (HFD) fed rats. Increasing doses of KBP-089 and liraglutide alone and in combination were studied with respect to their effects on body weight, food intake and glucose metabolism during a 9-week intervention study conducted in HFD rats. Further, the gastric emptying rate during an oral glucose tolerance was assessed. Treatment with KBP-089 and liraglutide dose-dependently lowered body weight 15% (at 2.5 μg/kg/day) and 7% (at 400 μg/kg/day) in HFD rats, respectively, while the combination resulted in a 21% body weight reduction, which was mirrored by reduction in fat depot sizes. Gastric emptying and glucose metabolism were improved, primarily by KBP-089, although liraglutide led to a reduction in fasting plasma glucagon. DACRAs complement GLP-1 on food intake, body weight, and glucose tolerance indicating the potential for an add-on therapy.


Lipoproteins of Listeria monocytogenes are critical for virulence and TLR2-mediated immune activation.
Numerous cell surface components of Listeria influence and regulate innate immune recognition and virulence. Here, we demonstrate that lipidation of prelipoproteins in Listeria monocytogenes is required to promote NF-kappaB activation via TLR2. In HeLa cells transiently expressing TLR2, L. monocytogenes and Listeria innocua mutants lacking the prolipoprotein diacylglyceryl transferase (lgt) gene are unable to induce TLR2-dependent activation of NF-kappaB, a property intrinsic to their isogenic parental strains. TLR2-dependent immune recognition is directed to secreted, soluble lipoproteins as evidenced by the sensitivity of the response to lipoprotein lipase. Studies of bone marrow-derived macrophages of C57BL/6 wild-type and TLR2-deficient mice infected with wild-type and lgt mutant strains indicate that the absence of host TLR2 receptor signaling has consequences similar to those of the absence of the bacterial TLR2 ligand, i.e., a delay in cellular immune responses directed toward the bacterium. Infection studies with the wild-type and TLR2(-/-) mice indicated attenuation of the lgt deletion mutant in both mouse strains, implying multiple roles of lipoproteins during infection. Further characterization of the Delta lgt mutant indicated that it is impaired for both invasion and intracellular survival and exhibits increased susceptibility to cationic peptides. Our studies identify lipoproteins as the immunologically active ligand of TLR2 and assign a critical role for this receptor in the recognition of these bacteria during infection, but they also reveal the overall importance of the lipoproteins for the pathogenicity of Listeria.


Association of thiol disulfide homeostasis with slow coronary flow.
Objective The aim of this study was to investigate the role of thiol disulfide homeostasis in the presence of slow coronary flow. Material and methods In this cross-sectional study, a total of 110 patients who admitted to our hospital between March 2014 and December 2015 were included in the study. There were 65 patients in the slow coronary flow, and 45 patients in the normal flow groups. Results We found significant differences between slow coronary flow and the normal flow groups for thiol disulfide homeostasis, and the results of our study indicated that hsCRP, and thiol disulfide ratio were independently associated with slow coronary flow. Conclusion Our study showed that thiol disulfide homeostasis was significantly and independently related to the presence of slow coronary flow.


[Effects of extremely low frequency electromagnetic radiation on cardiovascular system of workers].
To observe the exposure levels of extremely low frequency electromagnetic fields in workplaces and to analyze the effects of extremely low frequency electromagnetic radiation on cardiovascular system of occupationally exposed people. Intensity of electromagnetic fields in two workplaces (control and exposure groups) was detected with EFA-300 frequency electromagnetic field strength tester, and intensity of the noise was detected with AWA5610D integral sound level. The information of health physical indicators of 188 controls and 642 occupationally exposed workers was collected. Data were analyzed by SPSS17.0 statistic software. The intensity of electric fields and the magnetic fields in exposure groups was significantly higher than that in control group (P < 0.05), but there was no significant difference of noise between two workplaces (P > 0.05). The results of physical examination showed that the abnormal rates of HCY, ALT, AST, GGT, ECG in the exposure group were significantly higher than those in control group (P < 0.05). There were no differences of sex, age, height, weight between two groups (P > 0.05). Exposure to extremely low frequency electromagnetic radiation may have some effects on the cardiovascular system of workers.


Recognizing puzzling PD1 + infiltrates in marginal zone lymphoma by integrating clonal and mutational findings: pitfalls in both nodal and transformed splenic cases.
A marked increase in PD1-positive TFH cells in nodal MZL cases (NMZL) was reported previously and could prompt suspicion for a diagnosis of peripheral T-cell lymphoma (PTCL), especially angioimmunoblastic T-cell lymphoma (AITL). To demonstrate that the pitfall might exist not only in NMZL but also in transformed splenic MZL (tSMZL), two NMZL cases (70 y/o female with enlarged left cervical lymph node and 75 y/o male with generalized lymphadenopathy) and one case of tSMZL (47 y/o male with nodal and extranodal involvement) with obvious PD1-positive T-cell hyperplasia were described here. Although all their initial diagnoses were prompted to be AITL, they were comprehensively characterized by clinical features, morphologic, immunophenotypic, clonality, and targeted exosome sequencing (TES) findings. Case 1 and Case 2 were NMZL with increased PD1 + T cells in the "peripheral pattern" or "mixed peripheral and central pattern", and Case 3 was SMZL with abundant PD1-positive T cells in the "nodular pattern" that transformed to tSMZL (DLBCL) with PD1-positive T cells distributed in the "diffuse pattern." In addition to the monoclonal IG rearrangement and polyclonal TCR rearrangement results, TES demonstrated enriched and recurrent mutations in MZLs and failed to find aberrations described in AITL- or TFH-derived lymphomas. It is important to realize that this pitfall can also occur in more diagnostically difficult tSMZL cases; the integration of histopathology with clonality and mutation studies is also highlighted.


Intra-atrial activation pattern is useful to localize the areas of non-pulmonary vein triggers of atrial fibrillation.
Pulmonary vein isolation (PVI) is an established ablation procedure for atrial fibrillation (AF), however, PVI alone is insufficient to suppress AF recurrence. Non-pulmonary vein (non-PV) trigger ablation is one of the promising strategies beyond PVI and has been shown to be effective in refractory/persistent AF cases. To make non-PV trigger ablation more standardized, it is essential to develop a simple method to localize the origin of non-PV triggers. We retrospectively analyzed 37 non-PV triggers in 751 ablation sessions for symptomatic AF from January 2017 to December 2020. Regarding non-PV triggers, intra-atrial activation interval from the earliest in right atrium (RA) to proximal coronary sinus (CS) (RA-CSp) and that from the earliest in RA to distal CS (RA-CSd) obtained by a basically-positioned duodecapolar RA-CS catheter were compared among 3 originating non-PV areas [RA, atrial septum (SEP) and left atrium (LA)]. RA-CSp of RA non-PV trigger (56.4 ± 23.4 ms) was significantly longer than that of SEP non-PV (14.8 ± 25.6 ms, p = 0.019) and LA non-PV (-24.9 ± 27.9 ms, p = 0.0004). RA-CSd of RA non-PV (75.9 ± 32.1 ms) was significantly longer than that of SEP non-PV (34.2 ± 32.6 ms, p = 0.040) and LA non-PV (-13.3 ± 41.2 ms, p = 0.0008). RA-CSp and RA-CSd of SEP non-PV were significantly longer than those of LA non-PV (p = 0.022 and p = 0.016, respectively). Sensitivity and specificity of an algorithm to differentiate the area of non-PV trigger using RA-CSp (cut-off value: 50 ms) and RA-CSd (cut-off value: 0 ms) were 88% and 97% for RA non-PV, 81% and 73% for SEP non-PV, 65% and 95% for LA non-PV, respectively. The analysis of intra-atrial activation sequences was useful to differentiate non-PV trigger areas. A simple algorithm to localize the area of non-PV trigger would be helpful to identify non-PV trigger sites in AF ablation.


Replacing gastrostomy tubes with collapsible bumpers in pediatric patients: Is it safe to "cut" the tube and allow the bumper to pass enterally?
The "cut and push" technique for removal of percutaneous endoscopic gastrostomy (PEG) tubes with collapsible bumpers offers an alternative to the standard traction method of removal. This study compared the outcomes of these techniques. We completed a research ethics board-approved retrospective cohort study, identifying all patients less than 18years of age who underwent PEG tube removal at a children's hospital between December 2013 and December 2016. Outcomes included need for sedation and complications. We identified 127 children who had PEG tubes removed. Significantly fewer children required sedation with the cut and push group (1.1% vs. 60.6%, p≤0.001). Ten complications occurred, including 9 in the cut and push group (9.6% vs. 3%, p=0.23). Mean age at time of complication was significantly younger in the cut and push group (2.2 vs. 6.3years p=0.004). This is the largest reported series comparing the cut and push vs. traction removal methods. The cut and push technique significantly reduced the need for procedural sedation but was associated with increased risk of complications. While these data suggest that the technique is safe in older children, caution should be taken in younger children who appear to be more likely to vomit the residual bumper. Level III-Treatment study, Retrospective comparative study.


Comparative microdosimetry of photoelectrons and Compton electrons: an analysis in terms of generalized proximity functions.
A current discussion on mammography screening is focused on claims of high relative biological effectiveness (RBE) of mammography X rays compared to conventional 200 kV X rays. An earlier assessment in terms of the electron spectra of these radiations has led to the conclusion that the RBE is bound to be less than 2, regardless of specific model assumptions and the microdosimetric properties of electrons. The present study extends this result in terms of the microdosimetric proximity function, t(x), for electrons, which is essentially the spatial auto-correlation function of energy within particle tracks. If pairs of DNA lesions, e.g. chromosome breaks or deletions, bring about the observed damage, the value t(x) determines for a specified radiation the relative frequency of pairs of lesions a distance x apart. The effectiveness of the radiation is thus proportional to an average of the values of t(x) over the distances, x, for which lesions can combine. The analysis suggests that 15 keV electrons can have a low-dose relative biological effectiveness (RBE(M)) of 1.6 relative to 40 keV electrons if the interaction distances do not exceed about 1 micro m. An extension of the concept, the reduced proximity function, t(delta)(x), permits the inclusion of models with an energy threshold, such as delta = 100 eV, 500 eV or 2 keV, for the formation of each of the DNA lesions. This makes it possible to assess the potential impact of the Auger electrons which accompany most photoelectrons, but only a minority of the Compton electrons. It is found that the Auger electrons could make photoelectrons substantially more effective than Compton electrons at energies below 10 keV but not at energies above 15 keV. The conclusions obtained for the RBE of 15 keV electrons relative to 40 keV electrons will be roughly representative of the RBE of mammography X rays relative to conventional 200 kV X rays.


Regulation of global and specific mRNA translation by amino acids.
A continuous supply of a complete complement of essential amino acids is a prerequisite for maintenance of optimal rates of protein synthesis in both liver and skeletal muscle. Deprivation of even a single essential amino acid causes a decrease in the synthesis of essentially all cellular proteins through an inhibition of the initiation phase of mRNA translation. However, the synthesis of all proteins is not repressed equally. Specific subsets of proteins, in particular those encoded by mRNAs containing a 5'-terminal oligopyrimidine (TOP) motif, are affected to a much greater extent than most proteins. The specific decrease in TOP mRNA translation is a result of an inhibition of the ribosomal protein S6 kinase, S6K1, and a concomitant decline in S6 phosphorylation. Interestingly, many TOP mRNAs encode proteins involved in mRNA translation, such as elongation factors eEF1A and eEF2, as well as the ribosomal proteins. Thus, deprivation of essential amino acids not only directly and rapidly represses global mRNA translation, but also potentially results in a reduction in the capacity to synthesize protein.


Accuracy of Clinician Assessments of Medication Status in the Emergency Setting: A Comparison of Clinician Assessment of Antipsychotic Usage and Plasma Level Determination.
The present study aimed to assess the level of agreement between clinicians' routine assessments of medication status and plasma levels of commonly prescribed antipsychotic medications in patients presenting to an emergency room with an exacerbation of psychosis. We studied 105 patients presenting to an emergency room and admitted to an inpatient psychiatric unit with a diagnosis of schizophrenia, schizoaffective disorder, bipolar I disorder, or psychotic disorder not otherwise specified and a prior outpatient medication regimen including risperidone, olanzapine, quetiapine, aripiprazole, or paliperidone. Plasma levels of antipsychotics were drawn and sent to a specialty laboratory for testing. Of the 97 patients with usable samples, 33 (34%) were found to have therapeutic antipsychotic levels. Of these, 22 were judged by emergency room staff to be taking their medications at the appropriately prescribed doses, whereas 11 were judged not to be taking medication at all. Sixty-four patients were found to have subtherapeutic antipsychotic levels, 31 of whom had been assessed to be taking medication as prescribed. Emergency assessment of medication status predicted therapeutic and nontherapeutic antipsychotic levels at rates of 41.5% and 75%, respectively. Emergency staff assessment was statistically independent from the likelihood of having a therapeutic antipsychotic level. In patients presenting to emergency rooms with exacerbations of psychosis who are subsequently admitted to an inpatient facility, common assessments of medication status are frequently misleading. Readily available methods for rapidly measuring antipsychotic plasma levels in clinical settings are needed for clinicians to make reliable assessments.


Sun safety among farmers and farmworkers: a review.
Farmers and farmworkers face increased risks of skin cancer from exposure to solar ultraviolet radiation (UVR) when working outdoors. The objective of this study was to evaluate the evidence from behavioral and intervention studies from the peer-reviewed studies related to sun safety among farmers and farmworkers and identify any gaps in the literature. A comprehensive review was conducted between 1990 and 2013; 22 studies were identified related to behavior and health interventions of sun safety among these targeted groups. The inconsistency of data collection methods makes it difficult to estimate with accuracy any overall meaningful results of behavior. However, from the studies reviewed, farmers and farmworkers most frequently reported wearing some type of hat (23.6%-100%) as a primary method of protection from the sun when working outdoors. Female farmers were more likely than male farmers to use sunscreen and engage in indoor tanning behavior. All sun safety educational interventions studies reviewed reported positive increases in behavioral change. To a large degree, adequate sun protection is lacking and varies geographically among farmers. Although targeted education is key to making improvements on sun protection behavior, aggressive attempts have to be made. Studies related to farmworkers, sun safety behavior, and skin cancer are scarce and more research is needed in this area.


Isolation, Identification and Enzymatic Activity of Halotolerant and Halophilic Fungi from the Great Sebkha of Oran in Northwestern of Algeria.
The Great Sebkha of Oran is a closed depression located in northwestern of Algeria. Despite the ranking of this sebkha among the wetlands of global importance by Ramsar Convention in 2002, no studies on the fungal community in this area have been carried out. In our study, samples were collected from two different regions. The first region is characterized by halophilic vegetation and cereal crops and the second by a total absence of vegetation. The isolated strains were identified morphologically then by molecular analysis. The biotechnological interest of the strains was evaluated by testing their ability to grow at different concentration of NaCl and to produce extracellular enzymes (i.e., lipase, amylase, protease, and cellulase) on solid medium. The results showed that the soil of sebkha is alkaline, with the exception of the soil of cereal crops that is neutral, and extremely saline. In this work, the species Gymnoascus halophilus, Trichoderma gamsii, the two phytopathogenic fungi, Fusarium brachygibbosum and Penicillium allii, and the teleomorphic form of P. longicatenatum observed for the first time in this species, were isolated for the first time in Algeria. The halotolerance test revealed that the majority of the isolated are halotolerant. Wallemia sp. and two strains of G. halophilus are the only obligate halophilic strains. All strains are capable to secrete at least one of the four tested enzymes. The most interesting species presenting the highest enzymatic index were Aspergillus sp. strain A4, Chaetomium sp. strain H1, P. vinaceum, G. halophilus, Wallemia sp. and Ustilago cynodontis.


Congenital nephrotic syndrome and persistent hypothyroidism after bilateral nephrectomy.
Congenital nephrotic syndrome is commonly associated with hypothyroidism. Thyroid hormone supplementation is recommended as standard of care. The hypothyroidism is postulated to occur secondary to chronic massive proteinuria with loss of thyroid binding globulin, thyroid hormone and iodine. Previous reports have indicated that thyroxin may be discontinued following bilateral nephrectomy. We report our experience with one child with congenital nephrotic syndrome, Finnish type, and hypothyroidism who had a high requirement for thyroxin (100-150 microg/d) from infancy to 4 years of age. Hypothyroidism persisted despite bilateral nephrectomy and later following renal transplantation. However, his thyroxin requirement is now substantially lower (62.5 microg/d) at age 14 years. No goiter was detected clinically and antithyroid antibodies were negative. Thyroid ultrasound and 123I scan revealed a thyroid gland in the anatomically normal location. 123I uptake was elevated, 18% at 6 hours and 51% at 24 hours (normal values: 3-16% at 6 hours and 8-25% at 24 hours). Perchlorate was unavailable for a perchlorate washout study. We speculate that this patient may have an intrinsic problem with thyroid hormone synthesis. It is unclear whether this is related or coincidental to the Finnish nephrotic syndrome. We recommend following thyroid functions closely if thyroxin is discontinued following bilateral nephrectomies in Finnish type congenital nephrotic syndrome.


An Experimenting Field Approach for the Numerical Solution of Multiphase Flow in Porous Media.
In this work, we apply the experimenting pressure field technique to the problem of the flow of two or more immiscible phases in porous media. In this technique, a set of predefined pressure fields are introduced to the governing partial differential equations. This implies that the velocity vector field and the divergence at each cell of the solution mesh can be determined. However, since none of these fields is the true pressure field entailed by the boundary conditions and/or the source terms, the divergence at each cell will not be the correct one. Rather the residue which is the difference between the true divergence and the calculated one is obtained. These fields are designed such that these residuals are used to construct the matrix of coefficients of the pressure equation and the right-hand side. The experimenting pressure fields are generated in the solver routine and are fed to the different routines, which may be called physics routines, which return to the solver the elements of the matrix of coefficients. Therefore, this methodology separates the solver routines from the physics routines and therefore results in simpler, easy to construct, maintain, and update algorithms.


Prevalence of bacterial pathogens causing ocular infections in South India.
The eye may be infected from external sources or through intra-ocular invasion of micro-organisms carried by the blood stream. This study was undertaken to isolate and identify the specific bacterial pathogens causing ocular infections and to determine their in-vitro antibacterial susceptibilities to commonly used antibacterial agents. A retrospective analysis of all patients with clinically diagnosed bacterial ocular infections such as blepharitis, conjunctivitis, internal and external hordeolum, suppurative scleritis, canaliculitis, keratitis, dacryocystitis, preseptal cellulitis, endophthalmitis and panophthalmitis presenting between January 2005 and December 2005 was performed. Extra-ocular and intra-ocular specimens were collected and were subjected to direct microscopy and culture. A total of 756 patients with bacterial ocular infections were analyzed, of which 462(61%) eyes had adnexal bacterial infection, 217(28.7%) had corneal infection, 6 (0.8%) had scleral involvement and the remaining 71(9.39%) eyes had infection of the intra-ocular tissues. The predominant bacterial species isolated was S. aureus (195 of 776; 25%) followed by S. pneumoniae (169 of 776; 21.78%) and coagulase negative staphylococci (142 of 776; 18.3%). The largest number of gram-positive isolates were susceptible to cefazolin (545 of 624; 87.34%), chloramphenicol (522 of 624; 83.65%) and gatifloxacin (511 of 624; 81.89%) and gram-negative isolates were to amikacin (127 of 136; 93.38%), gatifloxacin (125 of 136; 91.91%) and ofloxacin (119 of 136; 87.5%), while aerobic actinomycetes were to amikacin (100%), gatifloxacin (14 of 16; 87.5%), chloramphenicol (14 of 16; 87.5%) and ofloxacin (13 of 16; 81.25%). S. aureus frequently causes infections of eyelids and conjunctiva, S. pneumoniae of lacrimal apparatus and cornea and coagulase negative staphylococci causes intra-ocular infections. Of all routinely used antibacterials tested, flouroquinolones, especially gatifloxacin and ofloxacin represented a good choice for treating bacterial ocular infections.


Conductance and gating of epithelial Na channels from rat cortical collecting tubule. Effects of luminal Na and Li.
The behavior of individual Na channels in the apical membrane of the rat cortical collecting tubule (CCT) was studied at different concentrations of the permeant ions Na and Li. Tubules were opened to expose their luminal surfaces and bathed in K-gluconate medium to minimize tubule-to-tubule variation in cell membrane potential and intracellular Na concentration. The patch-clamp technique was used to resolve currents through individual channels. The patch-clamp pipette was filled with solutions containing variable concentrations of either NaCl or LiCl. In one series of experiments, the concentrations were changed without substitutions. In another series, the ionic strength and Cl concentration were maintained constant by partial substitution of Li with N-methyl-D-glucamine (NMDG). In cell-attached patches, both the single-channel conductance (g) and the single-channel current (i) saturated as functions of the Na or Li activity in the pipette. Without NMDG, the saturation of i was well described by Michaelis-Menten kinetics with an apparent Km of approximately 20 mM activity for Na and approximately 50 mM activity for Li. Km was independent of voltage for both ions. With substitution for Li by NMDG, the apparent Km value for Li transport through the channels increased. The values of the probability of a channel's being open (Po) varied from patch to patch, but no effect of pipette ion activity on Po could be demonstrated. A weak dependence of Po on membrane voltage was observed, with hyperpolarization increasing Po by an average of 2.3%/mV.


Use of forward projection to correct patient motion during SPECT imaging.
We have developed an iterative method to correct axial and tangential patient motion occurring during tomographic acquisition. The method uses axial images reconstructed from the uncorrected projection images, which are then forward projected to form a basis for registering the original planar images and, in the process, directly seeks to establish a consistent data set. Our method can be applied to all SPECT scans including myocardial and brain SPECT. We demonstrate that the method is capable of detecting and quantitatively correcting for complex motion in both axial and tangential directions. Results from phantom experiments show excellent resolution and contrast recovery after simulated movement in both the axial and tangential directions and initial results with clinical data sets are encouraging.


Electron-beam writing of a relaxor ferroelectric polymer for multiplexing information storage and encryption.
To meet the strong demand for high-level encryption security, several efforts have been focused on developing new encryption techniques with high density and data security. Herein we employed a template-free electron beam lithography (EBL) technique to write various nanopatterns on poly(vinylidene fluoride-trifluoroethylene-chlorofluoroethylene) (P(VDF-TrFE-CTFE)) films and applied it to electron-beam/electric multiplexing memory. Furthermore, electron beams can arbitrarily tailor down the domain structure evolutions and dipole directions, as proved by a combination of AFM-IR and PFM. Finally, our devices could function concurrently as an electron-beam write-only-memory (EB-WOM) and FeRAM, where the information could be encoded with the metastable phase evolutions from the ferroelectric phase to the paraelectric phase and variable bi-level ferroelectric signals. Our systematic study provides an inspiring idea for the design of information encryption devices with high-security requirements in flexible electronic fields.


Fibronectin, Cryoglobulinemia and Immune Complexes in Sjogren's Syndrome Patients.
The problem of proper diagnosis, patient's status and disease progression is very actual for autoimmune diseases. Still the diagnosis of Sjogren's syndrome is more state of art than of science. Our preliminary investigations showed that serum fibronectin of elevated molecular weight may be probably considered as one of the diagnostic criteria in Sjogren's syndrome patients. The increase of molecular weight of FN chains from 220 kDa to 250 kDa derives from relative and absolute elevation in a content of N-acetylglucosamine in FN carbohydrate chains. The present results concern the presence of FN in cryoprecipitates and circulating immune complexes in Sjogren's syndrome patients and as it has been demonstrated this parameter may be used as a prognostic sign.


Mass spectrometric characterization of cholesterol esters and wax esters in epidermis of fetal, adult and keloidal human skin.
Mass spectrometry (MS) with chemical ionization was found to be a useful tool for characterizing epidermal cholesterol esters (CE) and wax esters (WE), and was applied to analyse them in the epidermis of fetal, adult and keloidal human skin. Increases in the concentrations of CE and WE had occurred by 20 weeks of gestation in association with increasing concentrations of ceramides and cholesterol sulphate. Although adult epidermis contained them in similar concentrations at 25-28 weeks of gestation (13-14% of the total less polar lipids), the molecular species were shown to differ between fetal and adult epidermis by MS. Cholesterol oleate comprised 45% of the total molecular species in adult CE, whereas saturated fatty acids with chain lengths of 15-19 were abundant in fetal CE. Also, unsaturated and shorter chain WE were abundant in adult epidermis in comparison with that in the fetal epidermis, the total chain lengths of fetal and adult WE being 34-42 with a mean chain length of 38.6, and 27-41 with a mean chain length of 34.0, respectively, and the unsaturated molecules in fetal and adult WE amounting to 29% and 45%, respectively. Also, CE and WE in the epidermis of keloidal skin were reduced to 67% and 20% of the levels in normal skin, respectively. Thus, epidermal CE and WE were shown to carry eligible structures for construction of the hydrophobic barrier at the skin and amniotic fluid interface as well as that at the skin and air interface.


Role of interferons in the therapy of melanoma.
A range of potent immunoregulatory molecules termed cytokines has become available for the therapy of human melanoma. Among the cytokines, the interferons (IFN) have been examined in great depth for the therapy of melanoma. IFN are able to modulate host effector cell function, including the tumor cytolytic function of lymphocytes and monocytes. IFN also have the capacity to regulate the distribution of circulating immunoregulatory (T) lymphocytes and the expression of tumor cell surface antigens, as well as class I and II products of the major histocompatibility locus. These activities of the IFN have led to their early application for treatment of human melanoma. The empirical evidence that IFN alpha exerts clinically significant anti-tumor effects against melanoma is reviewed, and evolving status of adjuvant trials of IFN alpha and gamma is noted. New indirect host-mediated anti-tumor activities that may potentially be manifest by IFN have yet to be fully harnessed. The opportunity to obtain meaningful anti-tumor activity in advanced disease or adjuvant settings, at dose ranges below those which are toxic (conventional maximal tolerable), are at hand. The U.S. cooperative groups [Eastern Cooperative Oncology Group (ECOG), Cancer and Leukemia Group B (CALGB), and South West Oncology Group (SWOG)] are studying IFN gamma in pursuit of this goal in advanced and adjuvant settings for melanoma and other tumors. The determination of the clinical role of IFN as biologic response modifiers demands equal commitment to the clinical assessment of immunobiologic mechanisms and anti-tumor effects. The immunologic assessment of IFN and a number of other cytokines is a major focus of the Pittsburgh Cancer Institute. Regional delivery of cytokines such as interleukin-2 (IL-2) may be the most appropriate and least toxic approach, given their half-life. Regional therapy by the intralesional route has yielded enhanced activity for a range of biologics, including bacillus Calmette-Guerin (BCG), IL-2, and tumor necrosis factor (TNF). Intralymphatic therapy with methanol extraction residue of BCG (MER-BCG) has been tested, and trials are now in progress with IL-2 to assess the optimal dosage by this route. It is likely that the optimal role of IFN and other cytokines will be found in combination with one another, and with different biologic modalities such as monoclonal antibodies and vaccines, to allow expansion and heightened activity of the desired effector cell populations in the host. Enhanced host toxicities, as well as anti-tumor effects, may require that special attention be devoted to optimal sequence of administration to enhance the therapeutic index.


Enhanced healing of diabetic wounds by topical administration of adipose tissue-derived stromal cells overexpressing stromal-derived factor-1: biodistribution and engraftment analysis by bioluminescent imaging.
Chronic ulcers represent a major health problem in diabetic patients resulting in pain and discomfort. Conventional therapy does not guarantee adequate wound repair. In diabetes, impaired healing is partly due to poor endothelial progenitor cells mobilisation and homing, with altered levels of the chemokine stromal-derived factor-1 (SDF-1) at the wound site. Adipose tissue-associated stromal cells (AT-SCs) can provide an accessible source of progenitor cells secreting proangiogenic factors and differentiating into endothelial-like cells. We demonstrated that topical administration of AT-SCs genetically modified ex vivo to overexpress SDF-1, promotes wound healing into diabetic mice. In particular, by in vivo bioluminescent imaging analysis, we monitored biodistribution and survival after transplantation of luciferase-expressing cells. In conclusion, this study indicates the therapeutic potential of AT-SCs administration in wound healing, through cell differentiation, enhanced cellular recruitment at the wound site, and paracrine effects associated with local growth-factors production.


[Buffon: time, change and history].
There is a longstanding and ongoing controversy about whether Buffon is to be regarded as a forerunner of evolutionism in the eighteenth century, or even as one of the founders of transformistic biology. There are good reasons to deny this claim. There are good reasons even to deny that the question which is going to be answered negatively is of particular importance. The present paper addresses the issue from a different angle. It analyzes the concept of time operative in the natural history writings of Buffon, and it delineates the articulation of the concepts of time, change, and history with its organizing impact on Buffon's discourse on earth and organisms. It is argued that although with his species concept Buffon tries to introduce the classical notion of a physical system into biology, in order to do so, he has to subvert it by an element of time. This guides him in considering various aspects of organic change, but by itself does not lead to a general perspective of transformation. On the other hand, in his Epoques de la nature, Buffon introduces a general law of geological change, thus arriving at something which could be called a physically intelligible history. The conquest of natural history by physics, in one and the same movement, leads to a subversion of physical geology by history, and prevents biology from becoming evolutionistic in the sense in which the nineteenth century understands this term.


[Surgical treatment of patients with duodenal ulcer].
Ulcer incidence in the Crimeahas increased during the last 9 years from 118.4 to 185.7 cases per 10,000 of adult population, being higher in South Coast and in mountains. From 125 patients with duodenal ulcer after conservative treatment only 12.8% have recovered (follow up for 8-10 years). 29.6% of patients underwent surgery; 1.6%--died without operations of ulcer, 35.2%--needed elective treatment. From 97 patients who died during 4 years of ulcer in Simferopol, 25 (25.8%) were not operated. They were aged and very old patients with long history of the disease. Among 9412 operations for ulcer there were 4.17% of lethal outcomes in perforated ulcer and 11.5%--in bleeding (22.18% being at the peak of hemorrhage); 1.45%--after elective resection of the stomach, 0.79%--after organ-saving operations with vagotomy, in SPV--0.56%. According to general hospital surgery data, there were no lethal outcomes after SPV and SPV with pyloroplasty (295 patients). As a conclusion it is stated, that surgery in ulcer should be made earlier, before complications.


Characterization of growth and metabolism of the haloalkaliphile Natronomonas pharaonis.
Natronomonas pharaonis is an archaeon adapted to two extreme conditions: high salt concentration and alkaline pH. It has become one of the model organisms for the study of extremophilic life. Here, we present a genome-scale, manually curated metabolic reconstruction for the microorganism. The reconstruction itself represents a knowledge base of the haloalkaliphile's metabolism and, as such, would greatly assist further investigations on archaeal pathways. In addition, we experimentally determined several parameters relevant to growth, including a characterization of the biomass composition and a quantification of carbon and oxygen consumption. Using the metabolic reconstruction and the experimental data, we formulated a constraints-based model which we used to analyze the behavior of the archaeon when grown on a single carbon source. Results of the analysis include the finding that Natronomonas pharaonis, when grown aerobically on acetate, uses a carbon to oxygen consumption ratio that is theoretically near-optimal with respect to growth and energy production. This supports the hypothesis that, under simple conditions, the microorganism optimizes its metabolism with respect to the two objectives. We also found that the archaeon has a very low carbon efficiency of only about 35%. This inefficiency is probably due to a very low P/O ratio as well as to the other difficulties posed by its extreme environment.


Evaluation of generic chiral liquid chromatography screens for pharmaceutical analysis.
Two different automated generic liquid chromatography screens for the separation of chiral compounds of pharmaceutical interest have been evaluated. The test set comprised 53 chemically diverse chiral compounds involving 55 enantiomeric pairs from the pharmaceutical industry (i.e. starting materials, synthetic intermediates and drug substances). The first screen utilised four polysaccharide-based columns with five mobile phases and showed enantioselectivity for 87% of the test compounds. The second screen employed three macrocyclic glycopeptide columns with two mobile phases and showed enantioselectivity for 65% of the test compounds. Merging of the two screening procedures resulted in an enantioselectivity for 96% of the chiral compounds. It is anticipated that the systematic use of the automated chiral HPLC screens described in this report will substantially reduce the necessary time for method development of pharmaceutically related chiral analytical methods.


Host selection by Culex pipiens mosquitoes and West Nile virus amplification.
Recent field studies have suggested that the dynamics of West Nile virus (WNV) transmission are influenced strongly by a few key super spreader bird species that function both as primary blood hosts of the vector mosquitoes (in particular Culex pipiens) and as reservoir-competent virus hosts. It has been hypothesized that human cases result from a shift in mosquito feeding from these key bird species to humans after abundance of the key birds species decreases. To test this paradigm, we performed a mosquito blood meal analysis integrating host-feeding patterns of Cx. pipiens, the principal vector of WNV in the eastern United States north of the latitude 36 degrees N and other mosquito species with robust measures of host availability, to determine host selection in a WNV-endemic area of suburban Chicago, Illinois, during 2005-2007. Results showed that Cx. pipiens fed predominantly (83%) on birds with a high diversity of species used as hosts (25 species). American robins (Turdus migratorius) were marginally overused and several species were underused on the basis of relative abundance measures, including the common grackle (Quiscalus quiscula), house sparrow (Passer domesticus), and European starling (Sturnus vulgaris). Culex pipiens also fed substantially on mammals (19%; 7 species with humans representing 16%). West Nile virus transmission intensified in July of both years at times when American robins were heavily fed upon, and then decreased when robin abundance decreased, after which other birds species were selected as hosts. There was no shift in feeding from birds to mammals coincident with emergence of human cases. Rather, bird feeding predominated when the onset of the human cases occurred. Measures of host abundance and competence and Cx. pipiens feeding preference were combined to estimate the amplification fractions of the different bird species. Predictions were that approximately 66% of WNV-infectious Cx. pipiens became infected from feeding on just a few species of birds, including American robins (35%), blue jays (17%, Cyanocitta cristata), and house finches (15%, Carpodacus mexicanus).


Role of membrane phospholipids in myocardial injury induced by ischemia and reperfusion.
Depletion of membrane phospholipids is known to be associated with myocardial ischemia, but its relationship to the injury involved with the reperfusion of ischemic myocardium is not known. The present study was designed to relate phospholipid degradation with reperfusion injury. The isolated in situ pig heart was subjected to 60 min of regional ischemia induced by occluding the left anterior descending (LAD) coronary artery and 60 min of global ischemia by hypothermic cardioplegic arrest followed by 60 min of reperfusion. The pigs were divided into two groups. In the treatment group, the heart was preperfused with mepacrine (0.05 mM), a known phospholipase inhibitor, for 15 min prior to LAD occlusion. In the control group, the total phospholipid content was not significantly decreased during LAD occlusion and arrest, but was reduced appreciably after reperfusion. Phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol followed a similar pattern. The lowering of these phospholipids during reperfusion was accompanied by enhancement of lysophosphatidylcholine. Mepacrine restored the normal levels of these phospholipids. During reperfusion, fatty acyl CoA synthetase, lysophospholipase, and lysophosphatidylcholine acyltransferase were depressed, whereas phospholipase A2 was enhanced. Mepacrine inhibited phospholipase A2, but had no effects on the other enzymes. Mepacrine also provided significant protection against reperfusion injury, as documented by the preservation of high-energy phosphate compounds and inhibition of the appearance of creatine kinase activity in the perfusate. These results suggest that membrane phospholipids play an important role in myocardial injury associated with ischemia and reperfusion, primarily because the deacylation-reacylation cycle of phospholipid biosynthesis becomes defective.


Consumption of flaxseed, a rich source of lignans, is associated with reduced breast cancer risk.
To investigate the association between intake of flaxseed-the richest source of dietary lignans (a class of phytoestrogens)-and breast cancer risk. A food frequency questionnaire was used to measure the consumption of flaxseed and flax bread by 2,999 women with breast cancer and 3,370 healthy control women who participated in the Ontario Women's Diet and Health Study (2002-2003). Logistic regression was used to investigate associations between consumption of flaxseed and flax bread and breast cancer risk. Confounding by established and suspected breast cancer risk factors, as well as dietary factors, was assessed. Flaxseed or flax bread was consumed at least weekly by 21 % of control women. None of the 19 variables assessed were identified as confounders of the associations between flaxseed or flax bread and breast cancer risk. Consumption of flaxseed was associated with a significant reduction in breast cancer risk (odds ratio (OR) = 0.82, 95 % confidence interval (CI) 0.69-0.97), as was consumption of flax bread (OR = 0.77, 95 % CI 0.67-0.89). This Canadian study is, to our knowledge, the first to report on the association between flaxseed alone and breast cancer risk and has found that flaxseed intake is associated with a reduction in breast cancer risk. As dietary intake of flaxseed is modifiable, this finding may be of public health importance with respect to breast cancer prevention.


Expanding the Conceptualization of Support in Low-Wage Carework: The Case of Home Care Aides and Client Death.
Home care aides are a rapidly growing, non-standard workforce who face numerous health risks and stressors on the job. While research shows that aides receive limited support from their agency employers, few studies have explored the wider range of support that aides use when navigating work stress and considered the implications of these arrangements. To investigate this question, we conducted 47 in-depth interviews with 29 home care aides in New York City, focused specifically on aides' use of support after client death. Theories of work stress, the social ecological framework, and feminist theories of care informed our research. Our analysis demonstrates aides' extensive reliance on personal sources of support and explores the challenges this can create in their lives and work, and, potentially, for their communities. We also document aides' efforts to cultivate support stemming from their home-based work environments. Home care aides' work stress thus emerges as both an occupational health and a community health issue. While employers should carry responsibility for preventing and mitigating work stress, moving toward health equity for marginalized careworkers requires investing in policy-level and community-level supports to bolster employer efforts, particularly as the home care industry becomes increasingly fragmented and non-standard.


Correlation of antinuclear antibody and anti-double-stranded DNA antibody with clinical response to infliximab in patients with rheumatoid arthritis: a retrospective clinical study.
The induction of antinuclear antibodies (ANAs) or anti-double-stranded (ds) -DNA antibodies (Abs) after infliximab (IFX) therapy in rheumatoid arthritis (RA) is a well-known phenomenon, but the correlation of such Abs with the clinical response to IFX has not yet been determined. The aims of this retrospective observational study were to examine the prevalence of positive ANA and anti-ds-DNA Abs before and after IFX therapy in patients with RA and to investigate whether an increased titer of such Abs is associated with the clinical efficacy of IFX. One hundred eleven RA patients who had received IFX were studied. ANA (indirect immunofluorescence with HEp-2 cells) and anti-ds-DNA Abs (Farr assay) results were examined before and after IFX therapy. The overall clinical response assessed by EULAR response criteria was as follows: good response in 55%, including remission in 38%; moderate response in 18%; and no response (NOR) in 27%. The positivity of ANA (≥ 1:160) and anti-ds-DNA Abs significantly increased from 25% to 40% (P = 0.03) and from 3% to 26% (P < 0.001) after IFX, respectively. EULAR response differed significantly according to the ANA titer before IFX (P = 0.001), and the efficacy of IFX became worse as the ANA titer before starting IFX increased. Furthermore, the differences in the clinical response of the ANA titer before IFX ≤ 1:80 and ≥ 1:160 were significant (good, moderate, and no response were 66%, 9%, and 25% in ≤ 1:80 group versus 26%, 33%, 41% in ≥ 1:160 group, respectively; P < 0.001). In 13 patients whose ANA had increased after IFX, 10 showed NOR, only one showed a good response, and none reached remission. These clinical responses were significantly different from ANA no-change patients. In 21 patients with positive anti-ds-DNA Abs after IFX, 16 showed NOR, only two showed a good response, and none reached remission. The present study suggests that the ANA titer before starting IFX predicts the clinical response to IFX. The increased titers of ANA or anti-ds-DNA Abs after IFX may be useful markers of NOR.


Examining the link between personality and laterality in a feral guppy Poecilia reticulata population.
This study examined whether variation in the strength and direction of lateralization in a detour task was linked with variation in three common personality measurements: boldness, activity and sociability, in a population of wild guppies Poecilia reticulata. Additionally, the aim was to determine whether any consistent correlations between these behavioural traits, known as behavioural syndromes, were present in the study population. The results revealed that all three personality traits were highly repeatable over time in both sexes. Evidence of a complex syndrome in the form of a correlation between boldness, sociability and activity was found; however, this relationship was only present in males. Males that were more active in a familiar environment emerged more quickly from shelter into a novel environment and were more social. In general, male P. reticulata were bold, active and antisocial compared to females, with these differences probably a reflection of opposing life-history strategies. Only a weak link between the strength of cerebral lateralisation and personality was discovered and this was mediated by sex.


Association between blood lipid levels and personality traits in young Korean women.
Abnormal lipid levels are important etiological factors associated with the development of atherosclerosis and with increased cardiovascular morbidity and mortality. Lipid levels are also influenced by lifestyle and behavioral factors, which suggests that personality traits might be related to abnormal lipid profiles. Studies on personality traits and lipid levels are relatively scarce in Korea. Therefore, the objective of this study was to examine the association between lipid levels and personality traits in young Korean women. A total of 1,701 young Korean women [mean age = 24.9±4.6 years (range 17-39)] who volunteered for personality trait evaluation were recruited for this study. Lipid levels, including total cholesterol, high density lipoprotein (HDL) cholesterol, and triglyceride, were measured in all subjects after an overnight fast, and a low density lipoprotein (LDL) cholesterol level was calculated. The study population was divided into abnormal and normal lipid level groups according to the clinical criteria. Personality traits were measured using the Revised NEO Personality Inventory for the Five-Factor Model of personality. High neuroticism was associated with low HDL cholesterol levels. Low extraversion and openness were associated with high levels of triglyceride. At the facet level, the association between personality and lipid levels were generally consistent. Angry hostility, self-consciousness, vulnerability to stress, activity, and straightforwardness were associated with HDL cholesterol levels. Activity, positive emotion, aesthetics, actions, and deliberation were associated with triglyceride. When applying clinical criteria, conscientiousness was less likely to have abnormal total cholesterol levels. Our results showed that the women with the low HDL cholesterol levels are like to be more neurotic and the hyperglycemic women are prone to lower extraversion and openness in Korea. Understanding the associations between blood lipid levels and personality traits may have a beneficial effect for the managing of dyslipidemia.


Microbial community- and metabolite dynamics of an anoxic dechlorinating bioreactor.
Monitoring and quantification of organohalide respiring bacteria is essential for optimization of on-site bioremediation of anoxic subsurface sites contaminated with chloroethenes. Molecular monitoring and model simulations were applied to determine degradation performance of an in situ dechlorinating bioreactor and its influence on the contamination plume. Dehalococcoides was the dominant dechlorinating microorganism as revealed by qPCR targeting 16S rRNA- and chloroethene reductive dehalogenase-encoding genes (tceA, vcrA, bvcA). The presence of all three reductive dehalogenases genes indicated coexistence of several distinct organohalide respiring bacterial populations in the bioreactor and groundwater. Mass balancing revealed that main dechlorinating activities were reduction of cis-dichloroethene and vinyl chloride. Analysis of growth kinetics showed that when performance of the bioreactor improved due to especially the addition of molasses, dechlorinating microorganisms were growing close to their maximum growth rate. Once near-complete dehalogenation was achieved, Dehalococcoides only grew slowly and population density did not further increase. The bioreactor influenced dechlorinating populations in the plume with subsequent decrease in chlorinated compound concentrations over time. In the present study, a combination of molecular diagnostics with mass-balancing and kinetic modeling improved insight into organohalide respiring bacteria and metabolite dynamics in an in situ dechlorinating bioreactor and showed its utility in monitoring bioremediation.


Neuroimmmune interactions of cannabinoids in neurogenesis: focus on interleukin-1β (IL-1β) signalling.
Neuroimmune networks and the brain endocannabinoid system contribute to the maintenance of neurogenesis. Activation of cannabinoid receptors suppresses chronic inflammatory responses through the attenuation of pro-inflammatory mediators. Moreover, the endocannabinoid system directs cell fate specification of NSCs (neural stem cells) in the CNS (central nervous system). The aim of our work is to understand better the relationship between the endocannabinoid and the IL-1β (interleukin-1β) associated signalling pathways and NSC biology, in order to develop therapeutical strategies on CNS diseases that may facilitate brain repair. NSCs express functional CB1 and CB2 cannabinoid receptors, DAGLα (diacylglycerol lipase α) and the NSC markers SOX-2 and nestin. We have investigated the role of CB1 and CB2 cannabinoid receptors in the control of NSC proliferation and in the release of immunomodulators [IL-1β and IL-1Ra (IL-1 receptor antagonist)] that control NSC fate decisions. Pharmacological blockade of CB1 and/or CB2 cannabinoid receptors abolish or decrease NSC proliferation, indicating a critical role for both CB1 and CB2 receptors in the proliferation of NSC via IL-1 signalling pathways. Thus the endocannabinoid system, which has neuroprotective and immunomodulatory actions mediated by IL-1 signalling cascades in the brain, could assist the process of proliferation and differentiation of embryonic or adult NSCs, and this may be of therapeutic interest in the emerging field of brain repair.


Award Winner in the Young Investigator Category, 2014 Society for Biomaterials Annual Meeting and Exposition, Denver, Colorado, April 16-19, 2014: Periodically perforated core-shell collagen biomaterials balance cell infiltration, bioactivity, and mechanical properties.
Orthopedic tissue engineering requires biomaterials with robust mechanics as well as adequate porosity and permeability to support cell motility, proliferation, and new extracellular matrix (ECM) synthesis. While collagen-glycosaminoglycan (CG) scaffolds have been developed for a range of tissue engineering applications, they exhibit poor mechanical properties. Building on previous work in our lab that described composite CG biomaterials containing a porous scaffold core and nonporous CG membrane shell inspired by mechanically efficient core-shell composites in nature, this study explores an approach to improve cellular infiltration and metabolic health within these core-shell composites. We use indentation analyses to demonstrate that CG membranes, while less permeable than porous CG scaffolds, show similar permeability to dense materials such as small intestine submucosa (SIS). We also describe a simple method to fabricate CG membranes with organized arrays of microscale perforations. We demonstrate that perforated membranes support improved tenocyte migration into CG scaffolds, and that migration is enhanced by platelet-derived growth factor BB-mediated chemotaxis. CG core-shell composites fabricated with perforated membranes display scaffold-membrane integration with significantly improved tensile properties compared to scaffolds without membrane shells. Finally, we show that perforated membrane-scaffold composites support sustained tenocyte metabolic activity as well as improved cell infiltration and reduced expression of hypoxia-inducible factor 1α compared to composites with nonperforated membranes. These results will guide the design of improved biomaterials for tendon repair that are mechanically competent while also supporting infiltration of exogenous cells and other extrinsic mediators of wound healing.


Psychosocial stressors in oral lichen planus.
Psychosomatic factors and their association with dermatological disorders are well recognized, yet their importance in oral lichen planus (OLP) is still debated. This study was done to determine the importance of psychosocial stressors in patients with OLP. An analytical age-sex matched double controlled study. Stratified serial random sampling was done for sample selection. The experimental group consisted of biopsy proven OLP subjects (n = 41), negative control consisted of apparently healthy general Out Patient Department (OPD) patients (n = 73) and positive controls were patients with burning mouth syndrome, atypical facial pain and myofacial pain dysfunction syndrome (n = 36). The General Health Questionnaire-version 28 (GHQ-28) and the Hospital Anxiety and Depression Scale (HADS) were used to evaluate psychosocial stressors in terms of stress, anxiety and depression respectively. The OLP patients had significantly higher stress (Z = 4.331; p < 0.05, significant), anxiety (Z = 4.260; p < 0.05, significant) and depression levels (Z = 4.942; p < 0.05, significant) than the negative controls when measured by GHQ and HADS respectively. Similar findings were noted between the two control groups, with higher stress (Z = 5.784; p < 0.05, significant), anxiety (Z = 6.416; p < 0.05, significant), and depression (Z = 4.841; p < 0.05, significant) levels in the positive control group. However, differences in stress (Z = 2.0416; p > 0.05, non-significant), anxiety (Z = 1.681; p > 0.05, non-significant) and depression levels (Z = 0.195; p > 0.05, non-significant) were found to be non-significant between OLP and positive control. Significantly higher stress, anxiety and depression levels were found in the OLP and positive control than the general population. No significant difference was noted between the OLP and the positive controls (in which psychosocial stressors are the sole etiology). These suggest that psychological stressors play an important role in the causation of OLP. It may be further hypothesized that these stressors form a starting point for the initiation of various autoimmune reactions, which have been shown to be contributory to the pathogenesis of OLP. Further longitudinal studies need to be done globally before definitive conclusions can be drawn.