Removal of fluoride in membrane-based water and wastewater treatment technologies: Performance review.
The presence of excess fluoride in aqueous media above local environmental standards (e.g., the U.S. Environmental Protection Agency (EPA) standard of 4 mg/L) affects the health of aquatic life. Excess fluoride in drinking water above the maximum contaminant level (e.g., the World Health Organization (WHO) standard of 1.5 mg/L) also affects the skeletal and nervous systems of humans. Fluoride removal from aqueous solutions is difficult using conventional electrochemical, precipitation, and adsorption methods owing to its ionic size and reactivity. Thus, new technologies have been introduced to reduce the fluoride concentration in industrial wastewater effluents and various drinking water sources. Membrane technology is one of the newer technologies found to be very effective in significantly reducing fluoride to desired standards levels; however, it has received less attention than other technologies because it is perceived as a costly process. This study critically reviewed the performance of various membrane process and compared it with effluent and zero liquid discharge (ZLD) standards. The performance review has been conducted with the consideration of the theoretical background, rejection mechanisms, technical viability, and parameters affecting flux and rejection performance. This review includes membrane systems investigated for the defluoridation process but operated under pressure (i.e., reverse osmosis [RO] and nanofiltration [NF]), temperature gradients (i.e., membrane distillation [MD]), electrical potential gradients (i.e., electrodialysis [ED] and Donnan dialysis [DD]), and concentration differences (i.e., forward osmosis [FO]). Moreover, the study also addressed the advantages, limitations, & applicable conditions of each membrane based defluoridation process.


Distribution of acid-etched, fixed, and removable prostheses in dental patients.
This report describes the pattern of tooth replacement for a random sample of adult dental patients in a major urban area in the northeastern United States. The data were collected by using a practitioner-based epidemiologic monitoring system that had been established with the local dental society. Nearly 90% of the randomly selected dentists collected the data on all adult patients seen during a 1-week period. The 2069 patients examined were predominantly regular users of dental care with a relatively even distribution across 10-year age groups. There was a slight preponderance of women in the sample (55%). There were no significant differences between men and women in terms of mean numbers of missing teeth. Overall, 92% were dentulous in both arches, 6% were edentulous in one arch, and 2% were totally edentulous. When the space was available for replacement, molars and premolars showed the lowest percentages of replacement in both arches for each age group. Overall, 14.4% of the replaced teeth were replaced by a fixed partial denture, of which acid-etched fixed partial dentures contributed 0.6% and conventional fixed partial dentures the remaining 13.8%. Removable prostheses replaced 85.6% of the missing teeth. The proportion of fixed replacements was highest in the youngest age groups and the proportion of removable replacements was dominating in the older age groups. Acid-etched fixed partial dentures were found most frequently in the youngest and oldest age groups.


Frailty and cognitive impairment: Unique challenges in the older emergency surgical patient.
Older patients (>65 years of age) admitted as general surgical emergencies increasingly require improved recognition of their specific needs relative to younger patients. Two such needs are frailty and cognitive impairment. These are evolving research areas that the emergency surgeon increasingly requires knowledge of to improve short- and long-term patient outcomes. This paper reviews the evidence for frailty and cognitive impairment in the acute surgical setting by defining frailty and cognitive impairment, introducing methods of diagnosis, discussing the influence on prognosis and proposing strategies to improve older patient outcomes. Frailty is present in 25% of the older surgical population. Using frailty-scoring tools, frailty was associated with a significantly longer hospital stay and higher mortality at 30 and 90 days after admission to an acute surgical unit. Cognitive impairment is present in a high number of older acute surgical patients (approximately 70%), whilst acute onset cognitive impairment, termed delirium, is documented in 18%. However, patients with delirium had significantly longer hospital stays and higher in-hospital mortality than those with cognitive impairment. Improved knowledge of frailty and delirium by the emergency surgeon allows the specialised needs of older surgical patients to be taken into account. Early recognition, and consideration of minimally invasive surgery or radiological intervention alongside potentially transferable successful elective interventions such as comprehensive geriatric assessment, may help to improve short- and long-term patient outcomes in this vulnerable population.


Juvenile fibrosarcoma of the orbit and eyelid. A study of five cases.
Five patients had juvenile fibrosarcoma of the orbit and eyelid. At initial surgical intervention, the patients ranged in age from newborn to 8 years (mean, 3 years 9 months). Three patients were male and two were female. Proptosis and/or painless swelling of the eyelid were the most common signs and symptoms. Four tumors grew within a few weeks or months, and all five were poorly circumscribed. They were composed of immature, spindle-shaped fibroblastic cells in a classic herringbone pattern or in interlacing fascicles. Hypercellularity and mitotic activity were present in all lesions. The differential diagnosis included rhabdomyosarcoma, fibromatosis, and fibrous histiocytoma. Electron microscopy confirmed the fibroblastic nature of the tumor cells in three cases. Follow-up ranged from one to 32 years (median, seven years). Two of five tumors recurred locally but none metastasized. Apparently surgical excision is the treatment of choice and the tumor has a favorable prognosis.


The 'factor of two' issue in mixed DNA profiles.
A commonly used idea in forensic fields is known as the 'hierarchy of propositions'. DNA analysts commonly report at the sub-source level in the hierarchy. This means that they simply comment on the probability of the evidence for the given propositions that consider contributors that lead to a DNA profile and not on the source of specific biological components, not the activity that led to the transfer or the offence that is reported to have occurred. However DNA analysts also commonly report at a level even lower than the sub-source level. In this 'sub-sub-source' level only reference comparisons to components of a mixture are reported. The difference between the sub-source level and sub-sub-source level is the difference between comparing an individual to a mixture as a whole, or comparing them to only one component of a mixture. This idea has been expressed in the past as the 'two trace' problem or the 'factor of two' problem. With the advent of expert systems that can provide a measure of weight of evidence in the form of a likelihood ratio (LR) for any mixture, resolvable or not, the distinction between these two levels becomes more important. In this paper we explore how the LR can be constructed to report correctly at the sub-source level, by taking contributor orders and genotype set orders into account. We include worked examples of the LR calculation to help explain this confusing issue.


Inhibition by white tea of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced colonic aberrant crypts in the F344 rat.
There is growing interest in the potential health benefits of tea, including the anticarcinogenic properties. We report here that white tea, the least processed form of tea, is a potent inhibitor of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced colonic aberrant crypts in the rat. Male Fischer 344 rats were treated for 8 wk with white tea (2% wt/vol) or drinking water alone, and on alternating days in experimental Weeks 3 and 4 the animals were given PhIP (150 mg/kg body wt p.o.) or vehicle alone. At the end of the study there were 5.65 +/- 0.81 and 1.31 +/- 0.27 (SD) aberrant crypt foci per colon in groups given PhIP and PhIP + white tea, respectively (n = 12, P < 0.05). No changes were detected in N-acetyltransferase or arylsulfotransferase activities compared with controls, but there was marked induction of ethoxyresorufin O-deethylase, methoxyresorufin O-demethylase, and UDP-glucuronosyltransferase after treatment with white tea. Western blot revealed corresponding increases in cytochrome P-450 1A1 and 1A2 proteins. Enzyme assays and Western blot also revealed induction of glutathione S-transferase by white tea. There was less parent compound and 4'-hydroxy-PhIP but more PhIP-4'-O-glucuronide and PhIP-4'-O-sulfate in the urine from rats given PhIP + white tea than in urine from animals given carcinogen + drinking water. The results indicate that white tea inhibits PhIP-induced aberrant crypt foci by altering the expression of carcinogen-metabolizing enzymes, such that there is increased ring hydroxylation at the 4' position coupled with enhanced phase 2 conjugation.


Outcome of alveolar bone grafting in patients with unilateral cleft lip and palate operated by one-stage method.
The aim of the study was the assessment of outcome of alveolar bone grafting in patients with unilateral cleft lip and palate operated on by the one-stage surgical procedure. The study concerned 108 patients (69 boys, 39 girls) with unilateral cleft of lip and palate operated by one stage method in the Surgical Department of Children and Adolescents IMC between 1994 and 2003. The reconstruction of alveolar process in these patients was carried out by autogenic bone graft at the age ranged from 1.5 to 16 years. The surgical procedure was the same regardless of age. The patients were divided into 3 groups according to age during this procedure: I- below 6 years, II - between 6 and 10 years, III - above 10 years. Evaluation of outcome of bone grafting was assessed on the base of Oslo classification and Chelsea scale. The relation between the patient's age at the time of bone grafting and the bone healing result was analyzed by the Spearman's rank correlation coefficient for the studied group as a whole, the age subgroups and the gender groups. Good results of treatment (I and II type) was obtained in 93 (86%) of patients, bad (III and IV type) in 15 patients according to Olso classification. According to Chelsea scale ultimate or satisfactory results (A, B, C) were obtained in 93 patients (86%) , unsatisfactory results (D, E, F) were obtained in 15 patients. Negative correlation between bone graft outcome and age of patients at the time of the procedure above 6 years was confirmed. No statistical significance in relation to sex of patients was found. According to two classifications (Oslo, Chelsea) good results of bone graft were obtained in 86% of patients. There was a relationship in outcome of bone grafting and the age of patients. The inter-gender correlation did not gain the statistical relevance.


Cost effectiveness of an intervention to increase uptake of hepatitis C virus testing and treatment (HepCATT): cluster randomised controlled trial in primary care.
To evaluate the effectiveness and cost effectiveness of a complex intervention in primary care that aims to increase uptake of hepatitis C virus (HCV) case finding and treatment. Pragmatic, two armed, practice level, cluster randomised controlled trial and economic evaluation. 45 general practices in South West England (22 randomised to intervention and 23 to control arm). Outcome data were collected from all intervention practices and 21/23 control practices. Total number of flagged patients was 24 473 (about 5% of practice list). Electronic algorithm and flag on practice systems identifying patients with HCV risk markers (such as history of opioid dependence or HCV tests with no evidence of referral to hepatology), staff educational training in HCV, and practice posters/leaflets to increase patients' awareness. Flagged patients were invited by letter for an HCV test (with one follow-up) and had on-screen pop-ups to encourage opportunistic testing. The intervention lasted one year, with practices recruited April to December 2016. Primary outcome: uptake of HCV testing. number of positive HCV tests and yield (proportion HCV positive); HCV treatment assessment at hepatology; cost effectiveness. Baseline HCV testing of flagged patients (six months before study start) was 608/13 097 (4.6%) in intervention practices and 380/11 376 (3.3%) in control practices. During the study 2071 (16%) of flagged patients in the intervention practices and 1163 (10%) in control practices were tested for HCV: overall intervention effect as an adjusted rate ratio of 1.59 (95% confidence interval 1.21 to 2.08; P<0.001). HCV antibodies were detected in 129 patients from intervention practices and 51 patients from control practices (adjusted rate ratio 2.24, 1.47 to 3.42) with weak evidence of an increase in yield (6.2% v 4.4%; adjusted risk ratio 1.40, 0.99 to 1.95). Referral and assessment increased in intervention practices compared with control practices (adjusted rate ratio 5.78, 1.6 to 21.6) with a risk difference of 1.3 per 1000 and a "number needed to help" of one extra HCV diagnosis, referral, and assessment per 792 (95% confidence interval 558 to 1883) patients flagged. The average cost of HCV case finding was £4.03 (95% confidence interval £2.27 to £5.80) per at risk patient and £3165 per additional patient assessed at hepatology. The incremental cost effectiveness ratio was £6212 per quality adjusted life year (QALY), with 92.5% probability of being below £20 000 per QALY. HepCATT had a modest impact but is a low cost intervention that merits optimisation and implementation as part of an NHS strategy to increase HCV testing and treatment. ISRCTN61788850.


[Study of amino acid composition and biosynthesis of protein components of the membrane system of corn plastids during biogenesis of chloroplasts].
The biosynthesis of membrane proteins in maize plastids at different stages of differentiation of the chloroplast lamellar system was studied. Prolamellar and lamellar system preparations were isolated from maize plastids, disintegrated by osmotic shock under hypotonic conditions. Changes in the amino acid composition of 14C membrane proteins were observed at all stages of chloroplast ultrastructure formation. The maximal level of the apolar amino acids was observed in the membrane fraction of chloroplasts. Washed membranes from maize proplastids and chloroplasts can be resolved into at least 14 protein bands on formic acid--urea polyacrylamide gel. It is pointed out that biogenesis process leads to the increase of lipophylic protein content in the chloroplast lamellae fraction.


Band slippage and erosion after laparoscopic gastric banding: a meta-analysis.
Laparoscopic adjustable gastric banding has the lowest morbidity and mortality rates among the common bariatric procedures. Troublesome complications associated with this procedure include band slippage and erosion, often requiring revisionary surgery. Rates of slippage have decreased, and this appears to be due to changes in surgical technique. In the authors' experience, units with a low slippage rate also have a low erosion rate and vice versa. Thus a systematic review was undertaken to investigate this relationship. Electronic databases were searched up to 31 December 2008. Publications focusing solely on laparoscopic adjustable gastric banding with at least 500 patients and a minimum follow-up period of 2 years were included in the study. Publications in languages other than English and those that failed to mention erosion and slippage rates were excluded. Multivariate meta-analyses were conducted separately for the pars flaccida group, the perigastric group, and the combined overall group to pool the average rates of both erosion and slippage for each paper included. The correlation between the occurrence rates for both erosion and slippage then was examined. The inclusion criteria were met by 19 studies. The mean rates of erosion and slippage were 1.03 and 4.93, respectively. The results demonstrated a statistically significant overall correlation between erosion and slippage rates (r = 0.48, p = 0.032). A very strong correlation between erosion and slippage was found if the perigastric technique of insertion was used (r = 0.99, p < 0.001). However, this correlation was not statistically significant where the pars flaccida technique of insertion was used (r = 0.34, p = 0.38). The high correlation rate between erosion and slippage for the perigastric group strongly suggests that these complications share a common pathophysiology. This correlation is reduced with the pars flaccida technique, suggesting that perhaps a different etiology is associated with erosion in these studies. Surgical techniques that help to eliminate lap band slippage should also reduce rates of erosion.


Brain tumor classification by proton MR spectroscopy: comparison of diagnostic accuracy at short and long TE.
Different TE can be used for obtaining MR spectra of brain tumors. The purpose of this study was to determine the influence of the TE used in brain tumor classification by comparing the performance of spectra obtained at two different TE (30 ms and 136 ms). One hundred fifty-one studies of patients with brain tumors (37 meningiomas, 12 low grade astrocytomas, 16 anaplastic astrocytomas, 54 glioblastomas, and 32 metastases) were retrospectively selected from a series of 378 consecutive examinations of brain masses. Single voxel proton MR spectroscopy at TE 30 ms and 136 ms was performed with point-resolved spectroscopy in all cases. Fitted areas of nine resonances of interest were normalized to water. Tumors were classified into four groups (meningioma, low grade astrocytoma, anaplastic astrocytoma, and glioblastoma-metastases) by means of linear discriminant analysis. The performance of linear discriminant analysis at each TE was assessed by using the leave-one-out method. Tumor classification was slightly better at short TE (123 [81%] of 151 cases correctly classified) than at long TE (118 [78%] of 151 cases correctly classified). Meningioma was the only group that showed higher sensitivity and specificity at long TE. Improved results were obtained when both TE were considered simultaneously: the suggested diagnosis was correct in 105 (94%) of 112 cases when both TE agreed, whereas the correct diagnosis was suggested by at least one TE in 136 (90%) of 151 cases. Short TE provides slightly better tumor classification, and results improve when both TE are considered simultaneously. Meningioma was the only tumor group in which long TE performed better than short TE.


Feasibility of real-time capture of routine clinical data in the electronic health record: a hospital-based, observational service-evaluation study.
The electronic health record (EHR) is underused in the hospital setting. The aim of this service evaluation study was to respond to National Health Service (NHS) Digital's ambition for a paperless NHS by capturing routinely collected cardiac outpatient data in the EHR to populate summary patient reports and provide a resource for audit and research. A PowerForm template was developed within the Cerner EHR, for real-time entry of routine clinical data by clinicians attending a cardiac outpatient clinic. Data captured within the PowerForm automatically populated a SmartTemplate to generate a view-only report that was immediately available for the patient and for electronic transmission to the referring general practitioner (GP). During the first 8 months, the PowerForm template was used in 61% (360/594) of consecutive outpatient referrals increasing from 42% to 77% during the course of the study. Structured patient reports were available for immediate sharing with the referring GP using Cerner Health Information Exchange technology while electronic transmission was successfully developed in a substudy of 64 cases, with direct delivery by the NHS Data Transfer Service in 29 cases and NHS mail in the remainder. In feedback, the report's immediate availability was considered very or extremely important by >80% of the patients and GPs who were surveyed. Both groups reported preference of the patient report to the conventional typed letter. Deidentified template data for all 360 patients were successfully captured within the Trust system, confirming availability of these routinely collected outpatient data for audit and research. Electronic template development tailored to the requirements of a specialist outpatient clinic facilitates capture of routinely collected data within the Cerner EHR. These data can be made available for audit and research. They can also be used to enhance communication by populating structured reports for immediate delivery to patients and GPs.


IFN-γ Triggered IFITM2 Expression to Induce Malignant Phenotype in Elderly GBM.
Advanced age is an important risk factor for the worse clinical presentation of gliomas, especially glioblastoma (GBM). The tumor microenvironment (TME) in elderly GBM (eGBM) patients is considerably different from that in young ones, which causes the inferior clinical outcome. Based on the data from the Chinese Glioma Genome Atlas RNA sequence (CGGA RNA-seq), the Cancer Genome Atlas RNA array (TCGA RNA-array), and gene set enrichment (GSE) 16011 array sets, the differential genes and function between eGBM (≥ 60 years old) and young GBM (yGBM, 20-60 years old) groups were explored. Immunohistochemistry (IHC) was utilized to depict the abundance of CD8+ cells (the main resource of IFN-γ) and IFITM2 protein expression in GBM samples. Furthermore, reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting (WB) were performed to verify the link between IFN-γ and IFITM2. Moreover, the small-interfering RNA (siRNA) of IFITM2 was used to explore the function of IFITM2 in GBM. Characterized by inflammatory TME and higher IFITM2 expression, eGBM harbored a shorter survival time. Chemotaxis and inflammatory cytokine-related genes were enriched in the eGBM group, with more infiltrative CD8+ T cells. The IHC of CD8 and IFITM2-staining could demonstrate these results. In addition, the IFN-γ response pathway was activated in eGBM and resulted in a dismal outcome. Next, it was found that IFITM2 triggered by IFN-γ played a key role in IFN-γ-induced malignant phenotype in eGBM.


[A comparative evaluation of the glycogen content in the peripheral blood of normal cattle and in chronic lymphoid leukemia].
Peripheral blood lymphocytes in cows of four groups (healthy, exposed to leucosis, those affected by leucosis at early or at developed stages) were tested for their glycogen contents by the two following methods: the semiquantitative PAS technique (Shabadash, 1947) and the quantitative cytofluorimetric variant of PAS reaction in the M. V. Kudriavtseva modification (1970). The results show no difference between the 1st and 2nd groups as concerns the number of leucocytes and the relation of the number of glycogen-positive cells to the share of lymphocytes in the peripheral blood. In the 3rd and 4th groups, the increase in glycogen in individual cells paralleled with the increase in the number of PAS-positive lymphocytes, according to the Shabadash method. On comparing the results of the study of glycogen contents in lymphocytes of healthy and leucosis suffering cows, the two methods used proved to coincide very well. Hence, both the methods may be used for the aims of diagnosis of hemoblastosis in farm animals.


Alterations of cAMP response element-binding activity in the aged rat brain in response to administration of rolipram, a cAMP-specific phosphodiesterase inhibitor.
Transcription factor, cAMP response element-binding protein (CREB), which is phosphorylated by cAMP-dependent kinase via an increase in cAMP, and regulates gene transcription by binding to the cAMP response element (CRE) on target genes. We examined age-dependent alterations in the DNA-binding activity of CREB in rat brain regions, and the effects of rolipram, a cAMP-specific phosphodiesterase (PDE) inhibitor on the CRE-binding activity by electrophoretic mobility-shift assay (EMSA). A marked age-dependent decrease in the CRE-binding activity was shown in all brain regions examined, especially in the basal forebrain, the striatum and the hippocampus. Furthermore, CRE-binding activities in the basal forebrain of both young-adult and aged rats significantly increased 2 h after rolipram administration (1 mg/kg, i.p.), and the rolipram treatment recovered the decreased CRE-binding activity in the aged rats. The saturation experiment in EMSA also revealed that rolipram reversed the decrease in the maximum CRE-bindings in the basal forebrain with aging. Since the 5' upstream region of the rat choline acetyltransferase (ChAT) gene contains CRE, and ChAT-positive neurons in the basal forebrain project to the frontal cortex and the hippocampus, rolipram may exert its previously reported ameliorating effect on the age-related reductions of ChAT activities in the frontal cortex and the hippocampus by phosphorylating CREB in the basal forebrain with activation of cAMP-dependent protein kinase via inhibition of PDE.


ALOX5 deficiency contributes to bladder cancer progression by mediating ferroptosis escape.
Ferroptosis is an iron-dependent form of regulated cell death driven by the lethal lipid peroxides. Previous studies have demonstrated that inducing ferroptosis holds great potential in cancer therapy, especially for patients with traditional therapy failure. However, cancer cells can acquire ferroptosis evasion during progression. To date, the therapeutic potential of inducing ferroptosis in bladder cancer (BCa) remains unclear, and whether a ferroptosis escape mechanism exists in BCa needs further investigation. This study verified that low pathological stage BCa cells were highly sensitive to RSL3-induced ferroptosis, whereas high pathological stage BCa cells exhibited obviously ferroptosis resistance. RNA-seq, RNAi-mediated loss-of-function, and CRISPR/Cas9 experiments demonstrated that ALOX5 deficiency was the crucial factor of BCa resistance to ferroptosis in vitro and in vivo. Mechanistically, we found that ALOX5 deficiency was regulated by EGR1 at the transcriptional level. Clinically, ALOX5 expression was decreased in BCa tissues, and its low expression was associated with poor survival. Collectively, this study uncovers a novel mechanism for BCa ferroptosis escape and proposes that ALOX5 may be a valuable therapeutic target and prognostic biomarker in BCa treatment.


Solubility as a limiting factor for expression of hepatitis A virus proteins in insect cell-baculovirus system.
The use of recombinant proteins may represent an alternative model to inactivated vaccines against hepatitis A virus (HAV). The present study aimed to express the VP1 protein of HAV in baculovirus expression vector system (BEVS). The VP1 was expressed intracellularly with molecular mass of 35 kDa. The VP1 was detected both in the soluble fraction and in the insoluble fraction of the lysate. The extracellular expression of VP1 was also attempted, but the protein remained inside the cell. To verify if hydrophobic characteristics would also be present in the HAV structural polyprotein, the expression of P1-2A protein was evaluated. The P1-2A polyprotein remained insoluble in the cellular extract, even in the early infection stages. These results suggest that HAV structural proteins are prone to form insoluble aggregates. The low solubility represents a drawback for production of large amounts of HAV proteins in BEVS.


Effects of water vapor on the reaction of CH2OO with NH3.
The reaction of the simplest Criegee intermediate, CH2OO, with ammonia and water vapor has been investigated at 278-308 K and under 100-760 Torr by monitoring the strong UV absorption of CH2OO. We found that the observed decay rate of CH2OO becomes much larger when ammonia and water vapor are both present; the combinational effect of ammonia and water vapor is significantly greater than the sum of their individual contributions, revealing a strong synergic effect. The kinetic data are consistent with a termolecular process of CH2OO + NH3 + H2O reaction, of which the reaction rate coefficient was determined to be kNH3+H2O = (8.2 ± 1.2) × 10-31 cm6 s-1 at 298 K with a negative activation energy, Ea = -8.0 ± 0.8 kcal mol-1 [kNH3+H2O(T) = 1.04 × 10-36 exp(4047/T)]. Quantum chemistry calculation (at the QCISD(T)/aug-cc-pVTZ//B3LYP/6-311+G(2d,2p) level) found a low-energy reaction pathway, on which water accepts a hydrogen atom (or proton) from ammonia and releases another hydrogen atom to the terminal oxygen of CH2OO. The predicted products are H2NCH2OOH and a new H2O molecule, indicating water catalysis. This reaction is very fast and probably barrierless, which poses a theoretical challenge to modeling the related kinetics.


Percutaneous Medial Collateral Ligament Repair and Posteromedial Corner Repair With Suture Tape Augmentation.
The medial collateral ligament (MCL) is among the most commonly injured structures of the knee. Most cases are managed nonoperatively; however, grade III injuries and injuries associated with multiligament injuries to the knee are often managed surgically. MCL reconstruction procedures are the most widely used surgical option, but modern advancements have seen a renewed interest in ligamentous repair that avoids graft-site morbidity. In addition, augmentation of the repair protects the ligament during the healing phase and allows early mobilization. This article describes, with video illustration, percutaneous MCL repair and posteromedial corner repair with suture tape augmentation.


Biological implications of the structural, antithrombin affinity and anticoagulant activity relationships among vertebrate heparins and heparan sulphates.
We analysed the distribution, structural characteristics, antithrombin-III-binding properties and anticoagulant activities of heparins and heparan sulphates isolated from the tissues of a wide range of vertebrates. Heparin has a curiously limited distribution, since it was absent from lower aquatic vertebrate species, present in only certain organs such as intestine in many higher vertebrates, and completely absent from the rabbit among mammals examined. The heparins were structurally diverse, and they exhibited a broad range of anticoagulant activities, from approx. 50% to 150% of average commercial heparins. Although there was a rough correlation between the anticoagulant potency of the starting isolate and the proportional content of material exhibiting high-affinity binding to the proteinase inhibitor antithrombin III, activities of high-affinity fractions from heparins low in activity overlapped those of low-affinity fractions from highly active heparins. Heparan sulphates, which in contrast were isolated from nearly all vertebrate organs, contained high-affinity subfractions constituting up to 5% of the starting material and possessing anticoagulant potencies of 2-30 units/mg. In consideration of the heparin data, we infer that its biological function is either species-specific or may be served by other molecular elements, and that there exists considerable diversity in the antithrombin-III-binding sequence of heparin. The more-generally distributed glycosaminoglycan heparan sulphate possesses within its variable structure a small high-affinity subfraction with low anticoagulant potency, whether isolated from aorta or other tissues. Although heparan sulphate appears to have an essential function at the cellular level, we suggest that this is probably not that of providing heparin-like antithrombotic effects on vascular surfaces.


Mobilizing community support in people receiving opioid-agonist treatment: A group approach.
This descriptive study evaluates a novel group intervention designed to help opioid-dependent patients in medication-assisted treatment identify and recruit drug-free individuals to support recovery efforts. The Social Network Activation Group works with patients who are actively using drugs and resistant to including drug-free family or friends in treatment. The group encourages patients to attend structured recovery, religious, or recreational activities in the community to find recovery support. For those with underutilized support, motivational interviewing and skills training are used to help patients resolve ambivalence and include family or friends in the treatment plan. Patients earn up to one methadone take-home each week that they attend the group and verify activity participation. They complete the group after introducing a drug-free family member or friend to their counselor. This study reports on a sample of 66 patients referred to this group as part of intensive outpatient treatment. Patients attended 71% of scheduled sessions and participated in a M = 4.3 activities. Mutual-help support groups (64%) and church (28%) were the activities most often attended. Thirty-six percent brought in a drug-free family or friend to meet their counselor. Family members were the most common choice (67%). The results demonstrate preliminary feasibility and mixed efficacy of the Social Network Activation Group for this highly select sample of patients, and provide additional evidence that many patients possess drug-free family or friends who are willing to support recovery efforts.


Asynchronous Embryo Transfer Followed by Comparative Transcriptomic Analysis of Conceptus Membranes and Endometrium Identifies Processes Important to the Establishment of Equine Pregnancy.
Preimplantation horse conceptuses require nutrients and signals from histotroph, the composition of which is regulated by luteal progesterone and conceptus-secreted factors. To distinguish progesterone and conceptus effects we shortened the period of endometrial progesterone-priming by asynchronous embryo transfer. Day 8 embryos were transferred to synchronous (day 8) or asynchronous (day 3) recipients, and RNA sequencing was performed on endometrium and conceptuses recovered 6 and 11 days later (embryo days 14 and 19). Asynchrony resulted in many more differentially expressed genes (DEGs) in conceptus membranes (3473) than endometrium (715). Gene ontology analysis identified upregulation in biological processes related to organogenesis and preventing apoptosis in synchronous conceptuses on day 14, and in cell adhesion and migration on day 19. Asynchrony also resulted in large numbers of DEGs related to 'extracellular exosome'. In endometrium, genes involved in immunity, the inflammatory response, and apoptosis regulation were upregulated during synchronous pregnancy and, again, many genes related to extracellular exosome were differentially expressed. Interestingly, only 14 genes were differentially expressed in endometrium recovered 6 days after synchronous versus 11 days after asynchronous transfer (day 14 recipient in both). Among these, KNG1 and IGFBP3 were consistently upregulated in synchronous endometrium. Furthermore bradykinin, an active peptide cleaved from KNG1, stimulated prostaglandin release by cultured trophectoderm cells. The horse conceptus thus responds to a negatively asynchronous uterus by extensively adjusting its transcriptome, whereas the endometrial transcriptome is modified only subtly by a more advanced conceptus.


Inhibitory effects of Bifidobacterium-fermented soy milk on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced rat mammary carcinogenesis, with a partial contribution of its component isoflavones.
High consumption of soybean and soybean-related products is hypothesized to contribute to protection against breast cancer. Soybean is a rich source of genistein, a putative cancer chemopreventive agent. Fermented soy milk (FSM), which is made of soy milk fermented with the Bifidobacterium breve strain Yakult, contains larger amounts of the isoflavone aglycones genistein and daidzein than unfermented soy milk. In the present study, we examined the effects of FSM and its component isoflavone mixture (genistein:daidzein 4:1) on 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine (PhIP)-induced mammary carcinogenesis in rats. Starting at 7 weeks of age, female Sprague-Dawley rats were given PhIP at a dose of 85 mg/kg body wt by intragastric administration four times a week for 2 weeks. They were fed control high fat basal diet or experimental high fat diet containing 10% FSM or 0.02 or 0.04% isoflavone mixture during and after carcinogen exposure. The incidences (percentage of rats with tumors) of mammary gland tumors were 71% in the control diet group, 51% in the FSM group and 68 and 61% in the groups treated with isoflavone mixture at 0.02 and 0.04%, respectively. Mammary tumor multiplicities (number of tumors per rat) were 1.2 +/- 0.2 for 10% FSM, 2.2 +/- 0.4 for 0.02% isoflavone mixture and 1.5 +/- 0.3 for 0.04% isoflavone mixture, being clearly smaller than the control diet value (2.6 +/- 0.5). Furthermore, feeding of FSM and the isoflavone mixture at both doses reduced the sizes of mammary tumors. Since the amounts of isoflavones in 10% FSM are approximately equivalent to those in the 0.02% isoflavone mixture, the chemopreventive activity of FSM could be partly attributable to the presence of isoflavones such as genistein and daidzein.


Quantitative profiling of phosphatidylcholine and phosphatidylethanolamine in a steatosis/fibrosis model of rat liver by nanoflow liquid chromatography/tandem mass spectrometry.
Quantitative analysis of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was carried out using a steatosis/fibrosis model of rat livers, which were induced by a chronic administration of carbon tetrachloride (CCl(4)). Intact phospholipid mixtures from each liver sample (from rats fed with 0.5 mL CCl(4)/kg three times a week for 30, 60, and 90 days) were analyzed by nanoflow liquid chromatography-electrospray ionization tandem mass spectrometry (nLC/ESI/MS/MS), and identifications of 37 PC and 19 PE species were made by collision-induced dissociation. The quantitative analysis utilized a multiple standard addition method with an internal standard, and the relationship between the MS peak intensities of different PC species and their carbon chain length was included for calibration. It was found that the total amount of PC and PE species decreased significantly with administration of CCl(4). While concentrations of most PC and PE species decreased to a great extent, three PEs and seven PCs were up-regulated more than twofold.


Is there an urban advantage in child survival in sub-saharan Africa? Evidence from 18 countries in the 1990s.
Evidence of higher child mortality of rural-to-urban migrants compared with urban nonmigrants is growing. However, less attention has been paid to comparing the situation of the same families before and after they migrate with the situation of urban-to-rural migrants. We use DHS data from 18 African countries to compare child mortality rates of six groups based on their mothers' migration status: rural nonmigrants; urban nonmigrants; rural-to-urban migrants before and after they migrate; and urban-to-rural migrants before and after they migrate. The results show that rural-to-urban migrants had, on average, lower child mortality before they migrated than rural nonmigrants, and that their mortality levels dropped further after they arrived in urban areas. We found no systematic evidence of higher child mortality for rural-to-urban migrants compared with urban nonmigrants. Urban-to-rural migrants had higher mortality in the urban areas, and their move to rural areas appeared advantageous because they experienced lower or similar child mortality after living in rural areas. After we control for known demographic and socioeconomic correlates of under-5 mortality, the urban advantage is greatly reduced and sometimes reversed. The results suggest that it may not be necessarily the place of residence that matters for child survival but, rather, access to services and economic opportunities.


Fatty acid modulation and polyamine block of GluK2 kainate receptors analyzed by scanning mutagenesis.
RNA editing of kainate receptor subunits at the Q/R site determines their susceptibility to inhibition by cis-unsaturated fatty acids as well as block by cytoplasmic polyamines. Channels comprised of unedited (Q) subunits are strongly blocked by polyamines, but insensitive to fatty acids, such as arachidonic acid (AA) and docosahexaenoic acid (DHA), whereas homomeric edited (R) channels resist polyamine block but are inhibited by AA and DHA. In the present study, we have analyzed fatty acid modulation of whole-cell currents mediated by homomeric recombinant GluK2 (formerly GluR6) channels with individual residues in the pore-loop, M1 and M3 transmembrane helices replaced by scanning mutagenesis. Our results define three abutting surfaces along the M1, M2, and M3 helices where gain-of-function substitutions render GluK2(Q) channels susceptible to fatty acid inhibition. In addition, we identify four locations in the M3 helix (F611, L614, S618, and T621) at the level of the central cavity where Arg substitution increases relative permeability to chloride and eliminates polyamine block. Remarkably, for two of these positions, L614R and S618R, exposure to fatty acids reduces the apparent chloride permeability and potentiates whole-cell currents approximately 5 and 2.5-fold, respectively. Together, our results suggest that AA and DHA alter the orientation of M3 in the open state, depending on contacts at the interface between M1, M2, and M3. Moreover, our results demonstrate the importance of side chains within the central cavity in determining ionic selectivity and block by cytoplasmic polyamines despite the inverted orientation of GluK2 as compared with potassium channels and other pore-loop family members.


Importance of dose intensity in neuro-oncology clinical trials: summary report of the Sixth Annual Meeting of the Blood-Brain Barrier Disruption Consortium.
Therapeutic options for the treatment of malignant brain tumors have been limited, in part, because of the presence of the blood-brain barrier. For this reason, the Sixth Annual Meeting of the Blood-Brain Barrier Disruption Consortium, the focus of which was the "Importance of Dose Intensity in Neuro-Oncology Clinical Trials," was convened in April 2000, at Government Camp, Mount Hood, Oregon. This meeting, which was supported by the National Cancer Institute, the National Institute of Neurological Disorders and Stroke, and the National Institute of Deafness and Other Communication Disorders, brought together clinicians and basic scientists from across the U.S. to discuss the role of dose intensity and enhanced chemotherapy delivery in the treatment of malignant brain tumors and to design multicenter clinical trials. Optimizing chemotherapy delivery to the CNS is crucial, particularly in view of recent progress identifying certain brain tumors as chemosensitive. The discovery that specific constellations of genetic alterations can predict which tumors are chemoresponsive, and can therefore more accurately predict prognosis, has important implications for delivery of intensive, effective chemotherapy regimens with acceptable toxicities. This report summarizes the discussions, future directions, and key questions regarding dose-intensive treatment of primary CNS lymphoma, CNS relapse of systemic non-Hodgkin's lymphoma, anaplastic oligodendroglioma, high-grade glioma, and metastatic cancer of the brain. The promising role of cytoenhancers and chemoprotectants as part of dose-intensive regimens for chemosensitive brain tumors and development of improved gene therapies for malignant gliomas are discussed.


Safer spaces in youth development programs and health in Canadian youth.
Engagement in youth programs is a potential means to promote health and well-being across populations of young people. Safer spaces in these youth programs are likely critical in fostering positive health outcomes, but current research on the links between safer spaces and health is limited. In this exploratory study, we examined links between program safety in youth development programs and minoritized status, and health-related quality of life (HRQoL) and psychosomatic health complaints. Participants (N = 282; Mean age = 16.97 years; SD = 2.97) self-identified across various minority status groups, including LGBTQ (30%) and a range of perceived income levels. We tested a statistical model in which safer spaces, LGBTQ status and perceived income predicted HRQoL and health complaints in youth development program participants. LGBTQ status and lower perceived income were related to lower HRQoL and more health complaints, and safer space in youth development programs was related to better HRQoL. We also found an interaction effect, such that safer spaces in youth programs appeared to be especially beneficial for HRQoL for youth with higher incomes. Findings reinforce past research on LGBTQ status and income as factors for youth wellness and mental health. Findings also suggest that perceived safer spaces in youth development programs support better HRQoL and lower health complaints, across populations of participating youth.


Aseptic loosening of total hip replacement. Macrophage expression of inducible nitric oxide synthase and cyclo-oxygenase-2, together with peroxynitrite formation, as a possible mechanism for early prosthesis failure.
Aseptic loosening is a major cause of failure of total hip arthroplasty. The adverse tissue response to prosthetic wear particles, with activation of cytokine and prostanoid production, contributes to bone loss around the implants. We have investigated the possibility that inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2) are expressed in macrophages in the pseudomembrane at the bone-implant interface, thereby contributing to the periprosthetic bone resorption. We also assessed whether peroxynitrite, a nitric oxide (NO)-derived oxidant associated with cellular injury, is generated in the membrane. Enzymatic activity of iNOS was measured using the arginine-citrulline assay technique and prostaglandin E2 (PGE2), as an indicator of COX-2 activity, was measured using an enzyme immunoassay. Cellular immunoreactivity for iNOS, nitrotyrosine (a marker of peroxynitrite-induced cellular injury) and COX-2 was assessed by quantitative peroxidase immunocytochemistry while immunofluorescence methods were used for subsequent co-localisation studies with CD68+ macrophages. The presence of calcium-independent iNOS activity and PGE2 production was confirmed in the homogenised interface membrane. Immunocytochemistry showed that periprosthetic CD68+ wear-debris-laden macrophages were the most prominent cell type immunoreactive for iNOS, nitrotyrosine and COX-2. Other periprosthetic inflammatory and resident cell types were also found to immunolocalise nitrotyrosine thereby suggesting peroxynitrite-induced protein nitrosylation and cellular damage not only in NO-producing CD68+ macrophages, but also in their neighbouring cells. These data indicate that both iNOS and COX-2 are expressed by CD68+ macrophages in the interface membrane and peroxynitrite-induced cellular damage is evident in such tissue. If high-output NO and peroxynitrite generation were to cause macrophage cell death, this would result in the release of phagocytosed wear debris into the extracellular matrix. A detrimental cycle of events would then be established with further phagocytosis by newly-recruited inflammatory cells and subsequent NO, peroxynitrite and prostanoid synthesis. Since both NO and PGE2 have been implicated in the induction and maintenance of chronic inflammation with resulting loss of bone, and peroxynitrite in the pathogenesis of disease states, they may be central to the pathogenesis of aseptic loosening.


[Glutathione-dependent enzymes and glucose-6-phosphate dehydrogenase of blood in patients with lymphosarcoma (non-Hodgkin's disease)].
Activities of glutathione-dependent enzymes and glucose-6-phosphate dehydrogenase (GPDH) were studied in blood of the patients with lymphosarcoma (LS). The activity of glutathione reductase (GR), glutathione dehydroascorbate reductase (GDAR), gamma-glutamyltranspeptidase (GGT) and G6PDH in plasma, leucocytes, lymphocytes and erythrocytes of peripheral blood in 30 patients (42-56 years) with LS and in 20 healthy have been determined with spectrophotometric methods (Humalyzer 2000 DE). Leucocytes and lymphocytes were separated from blood using Boyum method. Spearmen method used for correlative analysis. The levels of enzymes activity and results of correlative analysis showed an imbalance of antioxidative system defense and metabolic disturbances in patients with LS. The strong functional interrelation was estimated only between GR and G6PDH in the patients' lymphocytes (r=+0,716; p<0.0005). Interrelation was found between the levels of activity of antioxidative enzymes and activity (stage) of pathologic process, this may be used as the additional biochemical test for differential diagnostics of LS and estimation of the cells proliferative activity.


Association between route of inoculation with infectious bovine rhinotracheitis virus and site of recrudescence after dexamethasone treatment.
Four calves latently infected with infectious bovine rhinotracheitis virus (IBRV) were used to compare the ease of isolation of virus from neuronal ganglia and from mucosal surfaces. Two calves were slaughtered, and neuronal ganglia (cranial cervical, trigeminal, and 3rd and 4th sacral) were cocultivated on bovine fetal kidney cells. Virus was not isolated. Two calves given dexamethasone for 4 days were slaughtered on the 5th day. Virus was not isolated from cocultivated or macerated neuronal ganglia, but virus was isolated from nasal secretions taken from both calves on the day of slaughter. Eleven calves were inoculated with IBRV via different routes and were treated with dexamethasone 3 to 4 months after inoculation. virus was isolated from the nasal cavities, but not the vaginas of 6 heifers inoculated intranasally, and was isolated from the vaginas, but not the nasal cavities of 2 heifers inoculated intravaginally. Of 3 calves inoculated IV, virus was isolated from the nasal cavities of 3, from the oropharynxes of 2, and from the prepuce of 1.


Lung function tests in splenectomized beta-thalassemia/Hb E patients.
Pulmonary function tests were performed on 30 patients with beta-thalassemia/Hb E. Only one patient had normal pulmonary function. Arterial hypoxemia at rest was present in 22 of 30 patients (73.3%). Abnormal VC, FEV1, FEV1/FVC, and end tidal FEV1 were found in 29 (96.7%), 17 (56.7%), 6 (20.0%), and 17 (56.7%) patients, respectively. Single-breath carbon monoxide diffusing capacity was abnormal in one out of 11 patients (9.1%). These results suggest the presence of abnormal ventilatory function included restrictive, obstructive, and combined defects. The hypoxemia in thalassemia was probably due to ventilation/perfusion mismatch and a diffusion defect.


Urocanic acid may not be the photoreceptor for UV-induced suppression of contact hypersensitivity.
We have tested the hypothesis that urocanic acid is the photoreceptor molecule for ultraviolet radiation-induced systemic suppression of contact hypersensitivity in the mouse. Almost complete removal of urocanic acid by tape-stripping of exposed skin was not associated with abrogation of immune suppression. This finding makes it unlikely that urocanic acid is the chromophore.


Cost-effectiveness of a nurse practitioner-family physician model of care in a nursing home: controlled before and after study.
To examine the cost-effectiveness of a nurse practitioner-family physician model of care compared with family physician-only care in a Canadian nursing home. As demand for long-term care increases, alternative care models including nurse practitioners are being explored. Cost-effectiveness analysis using a controlled before-after design. The study included an 18-month 'before' period (2005-2006) and a 21-month 'after' time period (2007-2009). Data were abstracted from charts from 2008-2010. We calculated incremental cost-effectiveness ratios comparing the intervention (nurse practitioner-family physician model; n = 45) to internal (n = 65), external (n = 70) and combined internal/external family physician-only control groups, measured as the change in healthcare costs divided by the change in emergency department transfers/person-month. We assessed joint uncertainty around costs and effects using non-parametric bootstrapping and cost-effectiveness acceptability curves. Point estimates of the incremental cost-effectiveness ratio demonstrated the nurse practitioner-family physician model dominated the internal and combined control groups (i.e. was associated with smaller increases in costs and emergency department transfers/person-month). Compared with the external control, the intervention resulted in a smaller increase in costs and larger increase in emergency department transfers. Using a willingness-to-pay threshold of $1000 CAD/emergency department transfer, the probability the intervention was cost-effective compared with the internal, external and combined control groups was 26%, 21% and 25%. Due to uncertainty around the distribution of costs and effects, we were unable to make a definitive conclusion regarding the cost-effectiveness of the nurse practitioner-family physician model; however, these results suggest benefits that could be confirmed in a larger study.


Health status of native fish (Percilia gillissi and Trichomycterus areolatus) downstream of the discharge of effluent from a tertiary-treated elemental chlorine-free pulp mill in Chile.
Few data exist on the possible effects of pulp and paper effluent discharge on native fish populations in the Southern Hemisphere, relative to the research done in the Northern Hemisphere. The present research examined two native fish species (Trichomycterus areolatus and Percilia gillissi) for effects at both the molecular and individual level due to the discharge of effluent from a tertiary treated elemental chlorine-free pulp mill into a fluvial system in Central Chile over three seasons (February 2007, October 2007, January 2008). Different responses were observed between species and between sexes. There was an increase in the production of gonadal 17β-estradiol in the females of both species but a drop in 11-ketotestosterone production in P. gillissi males. Female gonadal size was increased, especially during the summer period, with corresponding increases the frequency of advanced oocyte development, and in the oocyte diameter in both species. Hepatic ethoxyresorufin-O-deethylase (EROD) activity was elevated for both species downstream of the discharge point, although overall it was higher in P. gillissi than T. areolatus. Decreases in the frequency of smaller-sized fish for both species, as well as a drop in the size of the adults downstream of the discharge point, were observed. The present study is the first evidence of endocrine disruption in native freshwater fish associated with modern pulp mills in South America. This study establishes possible links in the reproductive alterations observed at the subindividual and individual levels that could explain the changes observed at the population level.


MRI observations at return to play of clinically recovered hamstring injuries.
Previous studies have shown that MRI of fresh hamstring injuries have diagnostic and prognostic value. The clinical relevance of MRI at return to play (RTP) has not been clarified yet. The aim of this study is to describe MRI findings of clinically recovered hamstring injuries in amateur, elite and professional athletes that were cleared for RTP. We obtained MRI of 53 consecutive athletes with hamstring injuries within 5 days of injury and within 3 days of RTP. We assessed the following parameters: injured muscle, grading of injury, presence and extent of intramuscular signal abnormality. We recorded reinjuries within 2 months of RTP. MRIs of the initial injury showed 27 (51%) grade 1 and 26 (49%) grade 2 injuries. Median time to RTP was 28 days (range 12-76). On MRI at RTP 47 athletes (89%) had intramuscular increased signal intensity on fluid-sensitive sequences with a mean longitudinal length of 77 mm (±53) and a median cross-sectional area of 8% (range 0-90%) of the total muscle area. In 22 athletes (42%) there was abnormal intramuscular low-signal intensity. We recorded five reinjuries. 89% of the clinically recovered hamstring injuries showed intramuscular increased signal intensity on fluid-sensitive sequences on MRI. Normalisation of this increased signal intensity seems not required for a successful RTP. Low-signal intensity suggestive of newly developed fibrous tissues is observed in one-third of the clinically recovered hamstring injuries on MRI at RTP, but its clinical relevance and possible association with increased reinjury risk has to be determined.


The cytoplasmic domain of CD5 mediates both TCR/CD3-dependent and -independent diacylglycerol production.
CD5 is a 67-kDa surface glycoprotein found in association with the Ag receptor complex on both T and B lymphocytes. CD5 modulates Ag receptor-mediated immune responses, but the molecular mechanisms of its action remain unclear. In this respect, the assessment of the relative and unique contribution of CD5 in cell signaling events is a crucial point. We have used Jurkat variants and anti-CD5 mAbs to show that the CD5 signaling pathway is distinct from that used by the TCR/CD3 complex. We hereby identify two independent mechanisms of CD5-mediated diacylglycerol release by virtue of their different kinetics: 1) an early and transient diacylglycerol increase that results from the activation of a phosphatidylcholine-specific phospholipase C, and 2) a late and sustained increase that requires de novo phospholipid synthesis. Studies performed on a TCR/CD3-deficient Jurkat cell variant indicate that only the CD5-mediated phosphatidylcholine-specific phospholipase C activation is dependent on TCR/CD3 expression. Mutational analyses of CD5 demonstrate that both mechanisms are dependent on the integrity of the CD5 distal cytoplasmic region. Our results show that CD5 is a signaling molecule per se that uses mechanisms resembling those used by some cytokine receptors (such as IL-1 or TNF receptors) to modulate lymphocyte activation.


The Roles of Sex and Physical Activity in Gait and Knee Extensor Function With Age.
Older females experience higher rates of disability than males, potentially due to sex-specific differences in gait and muscle function. The authors evaluated the effects of age and physical activity (PA) on gait mechanics and knee extensor muscle function in males and females. Three groups of 20 individuals (each 10 females) participated: young (21-35 y) and highly and less active older (55-70 y) adults. Knee extensor strength and joint mechanics during preferred speed gait were collected before and after 30 minutes of walking. Age by sex and PA by sex interactions indicated older and less active older females had lower concentric knee extensor muscle power and larger hip extension moments than males. After 30 minutes of walking, older less active adults had larger decreases in knee extensor power than their highly active older counterparts, and older adults of both sexes had decreases in ankle dorsiflexion moments while young adults did not. These results suggest that older, particularly less active, adults are susceptible to knee extensor muscle fatigue from moderate activity. For older adults, high levels of PA may be necessary to preserve gait mechanics in response to a bout of exercise. This new information may be important for targeting interventions in at-risk older adults.


Extended Trochanteric Osteotomy in Revision Total Hip Arthroplasty: Contemporary Outcomes of 612 Hips.
Extended trochanteric osteotomies (ETOs) provide wide femoral and acetabular exposure, give direct access to the femoral medullary canal, and facilitate implant removal and new implant placement during selected revision total hip arthroplasties (THAs). Previous studies are limited by modest patient numbers and limited length of follow-up. The goals of the current study were to assess the union rate, complications, and outcomes of contemporary ETOs performed during revision THAs. From 2003 to 2013, 612 ETOs were performed during revision THAs at 1 institution using 2 techniques: Paprosky (laterally based osteotomy; n = 367) and Wagner (anteriorly based osteotomy; n = 245). The indications for the revision procedures were aseptic loosening (65%), periprosthetic joint infection (18%), periprosthetic fracture (6%), femoral implant fracture (5%), and other (6%). The mean patient age was 69 years, and 57% of the patients were male. The mean number of previous THAs was 1.6. The median duration of follow-up was 5 years (range, 2 to 13 years). The mean Harris hip scores increased from 57 preoperatively to 77 at the latest follow-up (p < 0.001). Radiographic and clinical union was achieved in 98% of the patients at a mean of 6 months (range, 1 to 24 months). The mean migration of the proximal trochanteric osteotomy fragment prior to union was 3 mm (range, 0 to 29 mm). ETO fragment migration of >1 cm occurred in 7% (37) of the 501 hips that had radiographic analysis. Nine hips (2%) had nonunion of the ETO. Intraoperative fracture of the ETO diaphyseal fragment occurred in 22 hips (4%), postoperative fracture of the ETO diaphyseal fragment occurred in 3 hips (0.5%), and postoperative fracture of the greater trochanter occurred in 41 hips (7%). Survivorship at 10 years free of revision for aseptic femoral loosening, free of femoral or acetabular component removal or revision for any reason, and free of reoperation for any reason was 97%, 91%, and 82%, respectively. This large series of ETOs shows that the union rate is high and clinically important trochanteric migration is infrequent. The most common complications are fracture of the osteotomy fragment intraoperatively or postoperatively. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Long-Range Proton Transfer in 7-Hydroxy-Quinoline-Based Azomethine Dyes: A Hidden Reason for the Low Efficiency.
In the tautomeric Schiff bases, derived from 7-hydroxyquinoline, two competitive channels are possible upon excitation of the enol tautomer, namely proton transfer (PT) through intramolecular hydrogen bonding to the corresponding keto form and trans-cis isomerization around the azomethine double bond. The former leads to switching, based on twist-assisted excited state intramolecular PT, where the long-range proton transfer can occur as a targeted process. The latter, determined by the flexibility of the crane part, reduces the efficiency of the main targeted process. In previously studied molecular switches based on the 7-hydroxyquinoline skeleton, only the intramolecular PT photo-process undergoing from the excited enol form towards the keto tautomer, which is in most cases barrierless, has been discussed. Therefore, in the current study, the ground state PT properties and isomerization of (E)-8-((phenylimino)methyl)quinolin-7-ol and (E)-8-(((pentafluorophenyl)imino)methyl)quinolin-7-ol are investigated in depth using the MP2 methodology, while the excited state energy profiles are calculated with the ADC(2) method. The obtained results are discussed in light of the existing experimental data.


Central interferon-alpha inhibits natural killer cytotoxicity through sympathetic innervation.
The brain has been known to produce high levels of interferon-alpha (IFN-alpha) during viral infections. We investigated the central and peripheral mechanisms of the brain IFN-alpha-induced suppression of natural killer (NK) cytotoxicity in the rat. The activity of NK cells in the spleen and the peripheral blood decreased 30-120 min after intracerebroventricular (icv) injection of recombinant human IFN-alpha of > 1,000 U but not after its intraperitoneal injection. This effect was antagonized by pretreatment with icv naltrexone (NLTX). Splenic denervation was observed to completely abolish the IFN-alpha-induced suppression of NK activity, whereas bilateral adrenalectomy did not. Furthermore, this immunosuppression was blocked by an icv injection of an antagonist of corticotropin-releasing factor (CRF), alpha-helical CRF-(9-41). The icv injection of CRF resulted in reduced NK activity, which was not affected by NLTX. The results suggest that brain IFN-alpha activates the CRF system through central opioid receptors and thereby suppresses the NK cytotoxicity predominantly through splenic sympathetic innervation.


Natural history of prostatism: high American Urological Association Symptom scores among community-dwelling men and women with urinary incontinence.
The American Urological Association Symptom Index (AUASI) has been reported to be nonspecific for benign prostatic hyperplasia. Comparable scores occur in patients with lower urinary tract symptoms of varying etiology, and even among women. The purpose of this study was to determine the association between the AUASI and urinary incontinence among community-dwelling men and women. In 1994, a randomly selected cohort of 1540 men and women aged 50 years or older from Olmsted County, Minnesota completed a self-administered questionnaire that assessed urinary symptom severity (AUASI score) and estimated the prevalence of urinary incontinence in the previous 12 months. The association between moderate to severe urinary symptom (AUASI score greater than 7) and urinary incontinence was investigated using multiple logistic regression, with adjustments for gender and age. Mean and median AUASI scores increased with age, and were higher among those respondents with urinary incontinence and among men. All seven urologic items in the AUASI were more prevalent among respondents with urinary incontinence and among men. Nocturia was highly prevalent among respondents with and without urinary incontinence, but urgency, frequency, and weak urinary stream were more prevalent among respondents with incontinence than among respondents without incontinence. When urinary incontinence, gender, and age were considered simultaneously, the respondents with urinary incontinence (odds ratio [OR] = 4.4, 95% confidence interval [CI] = 3.4, 5.5), men (OR = 1.9, 95% CI = 1.5, 2.5), and respondents 65 years or older (OR = 1.5, 95% CI = 1.2, 1.9) were more likely to have moderate to severe urinary symptoms. Our findings suggest that men and women with urinary incontinence and older men and women are significantly more likely to have moderate to severe urinary symptoms. These findings suggest that urinary incontinence may contribute to a high AUASI score in both sexes. Thus, these data indicate that the similarity in the distribution of the AUASI in men and women is, in part, an artifact introduced by the confounding effects of continence status.


Cyclosporine nephrotoxicity: sodium excretion, autoregulation, and angiotensin II.
Cyclosporine-induced nephrotoxicity (CIN) was studied in rats treated for 7 days with cyclosporine (10 mg x kg-1 x day-1 im) or vehicle (CON). CIN rats displayed characteristic reductions in glomerular filtration (GFR) and renal blood blood flow (RBF), and electron microscopy showed injury to proximal cells. Metabolic studies (7 day) showed significantly lower renal sodium excretion in conscious CIN rats compared with CON. In anesthetized rats at similar blood pressures, nephron GFR (SNGFR) was lower in CIN than CON, but fractional Na reabsorption was similar. In CIN, SNGFR, measured proximally to block flow to the sensing site of tubuloglomerular feedback (TGF) at the macula densa, was not significantly different than distal SNGFR. The rate of distal fluid delivery was significantly lower in CIN than in CON. Inhibition of the renin-angiotensin system (RAS) with captopril (CAP, 10 mg/kg iv), or saralasin (SAR, 0.3 mg x kg-1 x h-1 iv) caused marked arterial hypotension in CIN and a fall in renal vascular resistance (RVR). With arterial pressure controlled, CAP or SAR increased GFR and RBF, and reduced RVR in CIN, but did not reverse the renal deficits compared with similarly treated CON. RBF autoregulation in CIN was impaired between 90 and 140 mmHg but was partially restored by CAP. We conclude that both the filtered load and excretion rate of sodium in CIN are significantly reduced compared with controls, that SNGFR in CIN is not depressed by TGF in response to elevated distal fluid delivery, and that the RAS is not a primarily mediator of the renal vasoconstriction in CIN.


Biased T-cell receptor repertoires in patients with chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome).
Chromosome 22q11.2 deletion (del22q11.2) syndrome (DiGeorge syndrome/velocardiofacial syndrome) is a common syndrome typically consisting of congenital heart disease, hypoparathyroidism, developmental delay and immunodeficiency. Although a broad range of immunologic defects have been described in these patients, limited information is currently available on the diversity of the T-cell receptor (TCR) variable beta (BV) chain repertoire. The TCRBV repertoires of nine patients with del22q11.2 syndrome were determined by flow cytometry, fragment size analysis of the third complementarity determining region (CDR3 spectratyping) and sequencing of V(D)J regions. The rate of thymic output and the phenotype and function of peripheral T cells were also studied. Expanded TCRBV families were detected by flow cytometry in both CD4+ and CD8+ T cells. A decreased diversity of TCR repertoires was also demonstrated by CDR3 spectratyping, showing altered CDR3 profiles in the majority of TCRBV families investigated. The oligoclonal nature of abnormal peaks detected by CDR3 spectratyping was confirmed by the sequence analysis of the V(D)J regions. Thymic output, evaluated by measuring TCR rearrangement excision circles (TRECs), was significantly decreased in comparison with age-matched controls. Finally, a significant up-regulation in the percentage, but not in the absolute count, of activated CD4+ T cells (CD95+, CCR5+, HLA-DR+), IFN-gamma - and IL-2-expressing T cells was detected. These findings suggest that the diversity of CD4 and CD8 TCRBV repertoires is decreased in patients with del22q11.2 syndrome, possibly as a result of either impaired thymic function and/or increased T-cell activation.


Properties of threonine deaminase from a bacterium able to use threonine as sole source of carbon.
A threonine deaminase susceptible to inhibition by isoleucine was purified over 3,000-fold from extracts of Pseudomonas multivorans, a bacterium able to use threonine or alpha-ketobutyrate as sole source of carbon and energy. The enzyme was characterized with respect to molecular weight, dissociation to subunits, and apparent affinities for threonine, isoleucine, and several other ligands. Certain features of the enzyme including its reversible dissociation to subunits, its high constitutive activity, its marked stability, and high apparent orders of binding for threonine and isoleucine were unusual compared to those of isoleucine-inhibitable enzymes from other bacteria. These findings suggested some relationship between properties of the enzyme and the ability of P. multivorans to use threonine as sole carbon source. However, mutant studies ruled out a direct role of the enzyme in threonine catabolism and indicated that another enzyme, threonine dehydrogenase, is essential for growth on threonine.


Involvement of p53 R72P polymorphism in the association of MDM2-SNP309 with breast cancer.
The allelic variant MDM2-SNP309 (T>G) has been suggested to influence cancer development, but the clinical correlation between the risk allele and breast cancer remains controversial. The genetic background and the ethnicity of selected subgroups may influence the power of these risk genotypes. In this study, we investigated whether MDM2-SNP309 is associated with p53 R72P genetic polymorphism for the risk of breast cancer development in Asian Taiwanese, which has not been well-studied in this regard. Two hundred and fifty-five patients and 324 cancer-free controls were included, and we found that the MDM2-SNP309 TG and GG genotypes displayed marginally increased risks of breast cancer (GG vs. TT: OR = 1.7, 95% CI = 0.93 to 3.09; TG + TT vs. TT: OR = 1.57, 95% CI = 0.98 to 2.56). The breast cancer risk associated with MDM2-SNP309 was enhanced after stratification for the homozygous GG genotype at p53 codon 72 representing the Arg form of this genotype (GG vs. TT: OR = 3.7, 95% CI = 1.144 to 12.02; TG + GG vs. TT: OR = 2.7, 95% CI = 1.027 to 6.895). Also, the median age at diagnosis of patients with MDM2-SNP309 GG increased from 4 years earlier to 9 years earlier than TT patients after stratification for the GG genotype at p53 codon 72. Moreover, the G-allele of MDM2-SNP309 exhibited a stronger capacity than the T-allele to drive the full-length P2 promoter of the MDM2 gene in several human cell lines, suggesting that the association between MDM2-SNP309 and breast cancer is likely multifactorial rather than due to inconsistent gene expression in different cancer sources.


Docosahexaenoic acid,22:6n-3: Its roles in the structure and function of the brain.
Docosahexaenoic acid,22:6n-3 (DHA) and its metabolites are vital for the structure and functional brain development of the fetus and infants, and also for maintenance of healthy brain function of adults. DHA is thought to be an essential nutrient required throughout the life cycle for the maintenance of overall brain health. The mode of actions of DHA and its derivatives at both cellular and molecular levels in the brain are emerging. DHA is the major prevalent fatty acid in the brain membrane. The brain maintains its fatty acid levels mainly via the uptake of plasma free fatty acids. Therefore, circulating plasma DHA is significantly related to cognitive abilities during ageing and is inversely associated with cognitive decline. The signaling pathways of DHA and its metabolites are involved in neurogenesis, antinociceptive effects, anti-apoptotic effect, synaptic plasticity, Ca2+ homeostasis in brain diseases, and the functioning of nigrostriatal activities. Mechanisms of action of DHA metabolites on various processes in the brain are not yet well known. Epidemiological studies support a link between low habitual intake of DHA and a higher risk of brain disorders. A diet characterized by higher intakes of foods containing high in n-3 fatty acids, and/or lower intake of n-6 fatty acids was strongly associated with a lower Alzheimer's Disease and other brain disorders. Supplementation of DHA improves some behaviors associated with attention deficit hyperactivity disorder, bipolar disorder, schizophrenia, and impulsive behavior, as well as cognition. Nevertheless, the outcomes of trials with DHA supplementation have been controversial. Many intervention studies with DHA have shown an apparent benefit in brain function. However, clinical trials are needed for definitive conclusions. Dietary deficiency of n-3 fatty acids during fetal development in utero and the postnatal state has detrimental effects on cognitive abilities. Further research in humans is required to assess a variety of clinical outcomes, including quality of life and mental status, by supplementation of DHA.


The Illinois Women's Health Registry: advancing women's health research and education in Illinois, USA.
To achieve the goal of personalized medicine, we must first improve our understanding of the differences in health and illness between men and women. The purpose of the Illinois Women's Health Registry (USA) is to provide a research and education tool that advances scientific knowledge of sex- and gender-based differences in health and disease. Specifically, the Registry is a confidential 30-min health and lifestyle survey for female residents of Illinois over the age of 18 years. The survey includes questions regarding health, environment, health-related behaviors, symptoms and illnesses or conditions that a participant may have now or has had in the past. By enrolling in the Registry, women throughout the state are provided with information and access to clinical research studies that they may be eligible for, based on their self-reported health information. The Registry not only serves as a platform for recruitment into pivotal research studies, but also represents the beginning of a state-wide database that enables researchers to examine the collective de-identified health information provided by women living in Illinois. Ultimately, a cross-sectional and longitudinal analysis of these data will help to clarify the issues that women themselves identify as their main health concerns. In response to these concerns, specific research studies can be designed and launched, allowing us to eventually deliver tailored treatment and prevention options to women. Finally, by creating a reliable state-focused research tool, developed by staff that are trained in women's health research, we can compare health issues across the state and apply strategies for improvement where it is needed most. This article will provide examples of sex differences in disease, the lack of federal enforcement for inclusion of women in studies, researcher-perceived burdens and sex-based reasons as to why recruitment of women is considered to be more challenging. In addition, this article will discuss what a women's health registry is and why we need one in Illinois, how we have recruited women and our successes and challenges. Our goal is to inform the reader about the utility of a state-based tool and to provide a discussion regarding the lessons learned in order to aid other states in implementing this kind of program.


Realization of efficient semitransparent organic photovoltaic cells with metallic top electrodes: utilizing the tunable absorption asymmetry.
Efficient semitransparent organic photovoltaic (OPV) cells are presented in an inverted geometry employing ZnS/ Ag/ WO₃ (ZAW) as a top anode and ITO/ Cs₂CO₃ as a bottom cathode. Upon identification of the light absorption that differs depending on the illumination direction, the degree of the absorption asymmetry is tuned by varying the ZAW structure to maximize the efficiency for one direction or to balance it for both directions. Power conversion efficiency close to that of conventional opaque OPV cells is demonstrated in semitransparent cells for the ITO side illumination by taking advantage of the internal reflection occurring at the organic/ZAW interface. Cells with efficiencies that are reduced but balanced for both illumination directions are also demonstrated.


Path independent demodulation method for single image interferograms with closed fringes within the function space C(2).
In the last few years, works have been published about demodulating Single Fringe Pattern Images (SFPI) with closed fringes. The two best known methods are the regularized phase tracker (RPT), and the two-dimensional Hilbert Transform method (2D-HT). In both cases, the demodulation success depends strongly on the path followed to obtain the expected estimation. Therefore, both RPT and 2D-HT are path dependent methods. In this paper, we show a novel method to demodulate SFPI with closed fringes which follow arbitrary sequential paths. Through the work presented here, we introduce a new technique to demodulate SFPI with estimations within the function space C(2); in other words, estimations where the phase curvature is continuous. The technique developed here, uses a frequency estimator which searches into a frequency discrete set. It uses a second order potential regularizer to force the demodulation system to look into the function space C(2). The obtained estimator is a fast demodulator system for normalized SFPI with closed fringes. Some tests to demodulate SFPI with closed fringes using this technique following arbitrary paths are presented. The results are compared to those from RPT technique. Finally, an experimental normalized interferogram is demodulated with the herein suggested technique.


Overcoming barriers to role transition during an online post LPN to BN program.
Canadian Licensed Practical Nurses continuing their education in an online Bachelor of Nursing program face unique barriers as they transition towards a new and more complex nursing role. This qualitative descriptive study explored Post Licensed Practical Nurse to Bachelor of Nursing (Post LPN to BN) students' perceptions of their experiences during their education. George Kelly's (1955/1991) psychology of personal constructs, which seeks to understand how individuals perceive the world around them, was the theoretical framework for this three year longitudinal project in which 10 Post LPN to BN students were interviewed at the beginning, middle and end of their program. Transcripts from the interviews were analyzed and three key themes are presented to illustrate barriers that Post LPN to BN students faced and the strategies they implemented to overcame them. First, workplace mentors helped Post LPN to BN students apply their learning. Second, personal learning goals sustained their motivation. Third, time management strategies included terminating full time employment.


Experimental nonalcoholic steatohepatitis increases exposure to simvastatin hydroxy acid by decreasing hepatic organic anion transporting polypeptide expression.
Simvastatin (SIM)-induced myopathy is a dose-dependent adverse drug reaction (ADR) that has been reported to occur in 18.2% of patients receiving a 40- to 80-mg dose. The pharmacokinetics of SIM hydroxy acid (SIMA), the bioactive form of SIM, and the occurrence of SIM-induced myopathy are linked to the function of the organic anion transporting polypeptide (Oatp) hepatic uptake transporters. Genetic polymorphisms in SLCO1B1, the gene for human hepatic OATP1B1, cause decreased elimination of SIMA and increased risk of developing myopathy. Nonalcoholic steatohepatitis (NASH) is the most severe form of nonalcoholic fatty liver disease, and is known to alter drug transporter expression and drug disposition. The purpose of this study was to assess the metabolism and disposition of SIM in a diet-induced rodent model of NASH. Rats were fed a methionine- and choline-deficient diet for 8 weeks to induce NASH and SIM was administered intravenously. Diet-induced NASH caused increased plasma retention and decreased biliary excretion of SIMA due to decreased protein expression of multiple hepatic Oatps. SIM exhibited increased volume of distribution in NASH as evidenced by increased muscle, decreased plasma, and no change in biliary concentrations. Although Cyp3a and Cyp2c11 proteins were decreased in NASH, no alterations in SIM metabolism were observed. These data, in conjunction with our previous data showing that human NASH causes a coordinated downregulation of hepatic uptake transporters, suggest that NASH-mediated transporter regulation may play a role in altered SIMA disposition and the occurrence of myopathy.


Does loneliness lurk in temp work? Exploring the associations between temporary employment, loneliness at work and job satisfaction.
This research contributes to the limited literature concerning the determinants of loneliness at work, as well as to the literature on psychological outcomes associated with temporary work. More specifically, we are adding to the literature by exploring whether there is an association between working temporarily and loneliness at work and whether loneliness at work partly explains the association between working temporarily and job satisfaction. To this end, we analyse-by means of a mediation model-a unique sample of Flemish employees in the private sector. We find that employees with a temporary contract experience more loneliness at work as opposed to employees with a permanent contract. In addition, we discover that loneliness at work mediates the association between working temporarily and job satisfaction.


Web-Based Patient-Reported Outcomes Using the International Consortium for Health Outcome Measurement Dataset in a Major German University Hospital: Observational Study.
Collecting patient-reported outcome (PRO) data systematically enables objective evaluation of treatment and its related outcomes. Using disease-specific questionnaires developed by the International Consortium for Health Outcome Measurement (ICHOM) allows for comparison between physicians, hospitals, and even different countries. This pilot project aimed to establish a digital system to measure PROs for new patients with breast cancer who attended the Charité Breast Center This approach should serve as a blueprint to further expand the PRO measurement to other disease entities and departments. In November 2016, we implemented a Web-based system to collect PRO data at Charité Breast Center using the ICHOM dataset. All new patients at the Breast Center were enrolled and answered a predefined set of questions using a tablet computer. Once they started their treatment at Charité, automated emails were sent to the patients at predefined treatment points. Those emails contained a Web-based link through which they could access and answer questionnaires. By now, 541 patients have been enrolled and 2470 questionnaires initiated. Overall, 9.4% (51/541) of the patients were under the age of 40 years, 49.7% (269/541) between 40 and 60 years, 39.6% (214/541) between 60 and 80 years, and 1.3% (7/541) over the age of 80 years. The average return rate of questionnaires was 67.0%. When asked about the preference regarding paper versus Web-based questionnaires, 6.0% (8/134) of the patients between 50 and 60 years, 6.0% (9/150) between 60 and 70 years, and 12.7% (9/71) over the age of 70 years preferred paper versions. Measuring PRO in patients with breast cancer in an automated electronic version is possible across all age ranges while simultaneously achieving a high return rate.


Cardiovascular changes during sudden ascent in a cable cabin to the moderate altitude.
Our aim was to test the hypothesis that the occurrence of extrasystoles in higher decennia is proportional to the altitude. The occurrence of supraventricular (SVPB) and ventricular (VEB) extrasystoles, values of systolic and diastolic blood pressure and the heart rate were studied in 20 healthy elderly men (50-64 years) during cable cabin transportation to a moderate altitude. These values were measured in stations located at 898 m, 1764 m, and 2632 m above sea level during the transportation in both directions. Our records show that the values of blood pressure and heart rate were within normal limits during the whole period of transportation. Both SVPB and VEB were increasing during the ascent and decreasing to the initial values during the descent compared to the values at altitude of 898 m. The highest values (6 to 7-times exceeding the initial ones) were measured at the summit. The results have demonstrated that the occurrence of SVPB and VEB is proportional to the altitude. The increased incidence in the number of extrasystoles is suggested to be mediated by beta-adrenoceptors.


Treatment with silybin-vitamin E-phospholipid complex in patients with hepatitis C infection.
The aim of this study was to evaluate the hepatoprotective and anti-inflammatory effects of silybin-phospholipids and vitamin E complex (SPV complex), by determining cytokine patterns and various markers of liver disease. Forty Caucasian patients with chronic HCV infection were recruited and divided into two groups: 30 were treated with SPV complex for 3 months, while the other 10 did not receive any treatment. Ten other subjects without HCV infection but with staeatosic diagnosis were recruited and treated with SPV complex. Biochemical and hepatic principal parameters were investigated at 0 (T0) and 3 months (T3). The group of HCV patients treated showed an improvement trend of hepatic indecises and viral load, and had a significant and persistent reduction of ALT (P = 0.02) and AST serum level (P = 0.01). In this group cytokines showed a statistically significant increase of IL-2 (P = 0.03) and IL-6 were significantly reduced (P = 0.02) at T0 and T3. After the treatment the group of hepatic steatosics showed a significant decrease in ALT (P = 0.02), AST (0.008), gammaGT (0.004) alkaline phosphatase (0.05), total cholesterol (P = 0.03), fasting glucose (P = 0.008), insulinemia (0.0006), HOMA value (0.002) and C-reactive protein (CRP; 0.04). There was a significant reduction of IFN-gamma, TNF-alpha, and IL-6 (P = 0.02, 0.05 and 0.04, respectively). The data suggest that the SPV complex exerts hepatoprotective, anti-inflammatory and antifibrotic effects. This new compound may therefore be useful in clinical practice in patients with chronic hepatitis C who cannot undergo conventional antiviral therapy.


Double-valve Libman-Sacks endocarditis: an entity that demands special consideration.
Valvular heart disease, with a propensity for the left valves, is the most important cardiac manifestation of systemic lupus erythematosus (SLE). Libman-Sacks endocarditis complicating SLE has rarely been reported to cause hemodynamically significant valvular lesions necessitating valve replacement. This report describes a young woman with moderate aortic regurgitation and moderate to severe mitral regurgitation due to Libman-Sacks endocarditis. Treatment consisted of aortic and mitral valve replacement with mechanical prostheses due to intractable heart failure. The patient's recovery was uneventful. A literature survey disclosed only nine reports of double-valve replacement in patients with SLE. These findings, together with the present experience, suggest that valvular disease in SLE changes frequently with time, appears to be temporally unrelated to the other clinical features of SLE, and is associated with substantial morbidity and mortality. Corticosteroid treatment may slow the progression of valvular regurgitation. If surgery is necessary, replacement with a mechanical valve may be better than with a bioprosthesis.


Thermal migration of molecular lipid films as a contactless fabrication strategy for lipid nanotube networks.
We demonstrate the contactless generation of lipid nanotube networks by means of thermally induced migration of flat giant unilamellar vesicles (FGUVs), covering micro-scale areas on oxidized aluminum surfaces. A temperature gradient with a reach of 20 μm was generated using a focused IR laser, leading to a surface adhesion gradient, along which FGUVs could be relocated. We report on suitable lipid-substrate combinations, highlighting the critical importance of the electrostatic interactions between the engineered substrate and the membrane for reversible migration of intact vesicles.


Mediterranean diet and antihypertensive drug use: a randomized controlled trial.
To examine in older individuals at high cardiovascular risk whether following a Mediterranean diet decreased the necessity of antihypertensive drugs and modulated their associated cardiovascular risk. In the PREvención con DIeta MEDiterránea study, we assessed whether volunteers randomly allocated to an intervention with a Mediterranean diet enriched with extra-virgin olive oil or nuts (relative to a low-fat control diet) disclosed differences in the risk of: initiating antihypertensive medication in nonusers at baseline (n = 2188); and escalating therapy in participants using one, two, or three drugs at baseline (n = 2361, n = 1579, and n = 554, respectively). We also assessed whether allocation to Mediterranean diet modified the association between antihypertensive drug use and incident cardiovascular events. Participants allocated to Mediterranean diet interventions were associated with lower risk of initiating antihypertensive therapy [5-year incidence rates: 47.1% in the control diet, 43.0% in MedDiets; hazard ratio = 0.84, 95% CI (0.74--0.97), in a model adjusted for age, sex, and recruitment site]. Volunteers using two drugs at baseline in the Mediterranean diet intervention enriched with extra-virgin olive oil decreased their risk of therapy escalation [5-year incidence rates: 22.9% in the control diet, 20.1% in the MedDiet; hazard ratio = 0.77, 95% CI (0.60--0.99)]. Allocation to Mediterranean diet interventions attenuated the association between antihypertensive therapy at baseline and incidence of major adverse cardiovascular events (P interaction = 0.003). In an older population at high cardiovascular risk, following a Mediterranean diet reduced the risk of initiating or escalating antihypertensive medication and attenuated cardiovascular risk in antihypertensive drug users.


Isolation and molecular evolutionary analysis of a cytochrome c gene from Oryza sativa (rice)
A cytochrome c gene, OsCc-1, from rice (Oryza sativa) has been isolated and analyzed. The OsCc-1 gene encodes a cytochrome c protein that is typical of higher-plant cytochrome c proteins. OsCc-1 consists of three exons separated by two introns that are 817 and 747 bp in length, respectively. From genomic DNA hybridization analysis, OsCc-1 appears to be one of possibly two cytochrome c genes in several Asian, American, and Indian rice species and varieties surveyed. A single, unique cytochrome c gene appears to be present in one African cultivated rice species. We performed comparative molecular evolutionary analyses of OsCc-1 and other cytochrome c genes. We calculated a unit evolutionary period of 19.4 Myr for cytochrome c DNA sequences, which agrees closely with previous estimates based on protein sequence comparisons.


Expression and Kinetics of Endogenous Cannabinoids in the Brain and Spinal Cord of a Spare Nerve Injury (SNI) Model of Neuropathic Pain.
The role of endogenous cannabinoids in neuropathic pain has been actively studied, among which 2-arachidonoyl glycerol (2-AG) has received the most attention. However, owing to its chemical properties, direct detection of 2-AG distribution in tissues is difficult. Moreover, although desorption electrospray ionization mass spectrometry imaging (DESI-MSI) has enabled the detection of 2-AG, its distribution in the brain and spinal cord of neuropathic pain models has not been reported. In this study, the expression and distribution of 2-AG in the brain and spinal cord of a spare nerve injury (SNI) mice model of neuropathic pain was examined using DESI-MSI. The brain and lumbar spinal cord were collected and analyzed on days 3, 7, and 21 after treatment. On days 3 and 7 after treatment, 2-AG expression in the SNI model was decreased in the hypothalamus, midbrain, and especially in the periaqueductal gray (PAG) region but increased in the lumbar spinal cord. On day 21, the SNI model showed decreased 2-AG expression in the hypothalamus, but the difference from the control was not significant. Furthermore, there were no differences in 2-AG expression between the lumbar spinal cord, midbrain, or PAG. These data suggest that 2-AG might be involved in pain control.


Clinical presentation of pertussis in unvaccinated and vaccinated children in the first six years of life.
Identifying the determinants of the clinical presentation of pertussis is important for the purposes of diagnosis, therapy, and control and for predicting the disease's clinical course and choosing an appropriate case definition for surveillance. Potential determinants include vaccination status, antibiotic treatment, age at diagnosis, and sex, although the available data are inconsistent. The objective of this study was to compare the clinical course of pertussis in unvaccinated and vaccinated children in a well-defined and strictly studied population and to identify determinants of the disease's clinical presentation. The clinical presentation of pertussis was studied in children who participated in a randomized, controlled clinical trial of efficacy of acellular pertussis vaccine. The children belonged to the same birth cohort and were followed from infancy to 6 years of age in 3 distinct periods (stages 1, 2, and 3). Children had received 1 of 2 three-component acellular pertussis vaccines produced by 2 manufacturers (diphtheria-tetanus-acellular pertussis from, Chiron Biocine [DTaP CB]; DTaP from SmithKline Beecham [DTaP SB]) or a diphtheria-tetanus vaccine only (DT; Chiron Biocine). Pertussis was confirmed through culture or serology. For each pertussis episode, information was collected on age at onset, sex, type of vaccine received, antibiotic treatment, culture results, duration of cough, spasmodic cough, and other symptoms. The simultaneous effect of potential determinants of clinical presentation of pertussis on the duration of cough and spasmodic cough was studied through analysis of variance models. The analysis was conducted on 788 laboratory-confirmed cases of pertussis. The median duration of cough in DT recipients varied from 52 to 61 days across the 3 stages, whereas the median duration of cough in DTaP recipients varied from 29 to 39 days. The median duration of spasmodic cough varied from 20 to 45 days in DT recipients and from 14 to 29 days in DTaP recipients. The results of the analysis of variance models showed that vaccination against pertussis reduced the length of cough from 3 to 10 days and the length of spasmodic cough from 4 to 8 days. Culture-positive patients had a cough 11 to 22 days longer and a spasmodic cough 12 to 22 days longer than culture-negative patients. Children who received an antibiotic had a duration of cough 6 to 11 days longer and spasmodic cough 4 to 13 days longer than untreated patients. Girls had a duration of spasmodic cough 7 days longer than boys only after 3 years of age. Age was directly related to duration of cough, whereas it was inversely related to duration of spasmodic cough after 3 years of age. Duration of cough can be greatly influenced by vaccination status. A positive culture for Bordetella pertussis is more frequently found in patients with long duration of cough, and antibiotic therapy may be a marker of severe disease. Gender may affect the clinical presentation of pertussis only after infancy. Pertussis in older children may be characterized by short duration of spasmodic cough. These results should be taken into account in the clinical evaluation of patients with suspected pertussis. Clinical case definitions for the purpose of surveillance based on the presence of 2 weeks of spasmodic cough may not be appropriate where pertussis vaccination uptake is high.