Costs and effectiveness of travoprost versus a dorzolamide + timolol fixed combination in first-line treatment of glaucoma: analysis conducted on the United Kingdom General Practitioner Research Database.
To compare the effectiveness and associated costs of travoprost versus a fixed combination of dorzolamide + timolol as first-line therapy for glaucoma according to data collected by the United Kingdom General Practitioner Research Database (UK-GPRD). Patients with a diagnosis of ocular hypertension, glaucoma, or who had been treated topically by surgery or laser therapy were selected. Patients starting first-line treatment with travoprost or a fixed dorzolamide + timolol combination were included. Times to treatment failure were compared with an adjusted Cox model. Cost and treatment failure defined as a prescription change (adding or removing a topical treatment, or initiating laser therapy or surgery). 56 612 patients were extracted from the database and 39 808 patients received at least one topical prescription for IOP-lowering (intraocular pressure) therapy. Of these, 639 were treated with travoprost and 387 with dorzolamide + timolol, as first-line therapies. No significant difference was found between patient characteristics. Patients were aged 70.0 years and 48.5% were male. At 1 year, treatment failure was experienced by 30.4% of patients receiving travoprost and 49.4% receiving dorzolamide + timolol (p < 0.001). The hazard ratio for failure was 0.79 (p < 0.03) less with travoprost, after adjusting on age, gender, comorbidities and duration of follow-up. Adjusted annual costs of glaucoma management were significantly (p < 0.001) lower with travoprost ( pound198.31) than with dorzolamide + timolol ( pound312.21). This retrospective costs and consequences analysis study showed that travoprost is more efficient than dorzolamide + timolol as first-line therapy for glaucoma patients. Patients continued longer with first-line treatment when prescribed travoprost at a lower cost.


Anti-tumor immunity elicited by adenovirus encoding AdhTrp2 or AdmTrp2 without vitiligo.
To compare the difference in tumor immunity and autoimmunity elicited by adenovirus (Ad) encoding human or murine tyrosinase-related protein 2 (AdhTRP2 or AdmTRP2), and to find the most effective way to induce immunity by AdhTRP2 or AdmTRP2, C57BL/6 mice were immunized with AdhTRP2 or AdmTRP2 intramuscularly at different doses of 10(5), 10(6), 10(7) and 10(8) separately (10 mice for each dose). Two weeks after the immunization, in vivo CTL assay and intracellular staining (ICS) of IFN-gamma were carried out to analyze the dose-effect relationship. Tumor growth and vitiligo (as an sign of autoimmunity) were observed until 3 months after challenge with 10(5) B16F10 tumor cells. The results showed that Ad encoding AdmTrp2 induced weak tumor immune response. Similar immunization with AdhTrp-2 elicited stronger protective immunity. CTL activity and IFN-gamma-produced CD8+T cells were directly proportional to dose of AdhTrp2 or AdmTrp2. Moreover, AdhTrp2 group showed tumor rejection in 100% of challenged mice till the end of 3rd month while 60% of mice immunized with AdmTrp2 were protected against tumor. In the whole process of this experiment, no vitiligo was observed in mice immunized either with AdhTrp2 or AdmTrp2. It is concluded that anti-melanoma responses induced by genetic vaccination expressing xenoantigens breaks immune tolerance effectively and is able to elicit strong antigen-specific cytotoxic T cell response without vitiligo.


Adenosine 3',5'-monophosphate-dependent protein kinase(s) in diploid and SV40 transformed human fibroblasts.
Cyclic AMP-dependent protein kinases (EC 188.8.131.52; ATP:protein phosphotransferase) in the human diploid fibroblast WI-38 and an SV40-transformant WI-38-VA13-2RA (VA13) have been compared on the basis of their concentrations in cells, isoenzyme composition and susceptibility to hormonal activation. In high population density cultures, total soluble cyclic AMP-dependent kinase activities measured with histone were essentially the same in WI-38 and VA13. Two soluble protein kinase forms separated by chromatography on DEAE-cellulose were present in both cell lines. The concentration of cyclic AMP required for half-maximal activation of both enzyme forms was 10-30 nM. Overall kinase stimulation was greater for the Peak I enzymes. Kinase activation induced in the presence of 0.5 M KCl was more rapid and complete for the Peak I enzymes. Under conditions which elevated the concentration of cyclic AMP in WI-38 and VA13 cells the activities of the soluble histone kinases were increased. Incubation of the cells with either of 5.7 micronM prostaglandin E1 or 1 micronM isopropylnorepinephrine induced complete activation of the cyclic AMP-dependent histone kinases within 5 min and maintained the effect for 20 min. When intracellular cyclic AMP levels were raised by prostaglandin E1, activation of glycogen phosphorylase (assayed-AMP) suggested that this enzyme cascade involving cyclic AMP-dependent protein kinase(s) was intact and responsive in both cell lines.


Evaluation of hearing and auditory nerve function by combining ABR, DPOAE and eABR tests into a single recording session.
In this article, we describe an efficient method for testing both auditory receptor and auditory nerve function in a single recording session. Auditory receptor function is tested in response to pure tone, tone burst and click acoustic stimuli (i.e. distortion products of otoacoustic emissions, DPOAE; and auditory-evoked brainstem responses, ABR). The function of the auditory neurons and nerve is measured in response to direct electric current stimulation (i.e. electrically evoked auditory brainstem responses, eABR). All measurements were obtained from anesthetized laboratory rats during single recording sessions using hardware and software stimulation and analysis programs developed by Intelligent Hearing Systems, Miami, FL.


Apical distribution of HFE-beta2-microglobulin is associated with inhibition of apical iron uptake in intestinal epithelia cells.
Mutations in the HFE gene result in hereditary hemochromatosis, a disorder of iron metabolism characterized by increased intestinal iron absorption. Based on the observation that ectopic expression of HFE strongly inhibits apical iron uptake (Arredondo et al., 2001, FASEB J 15, 1276-1278), a negative regulation of HFE on the apical membrane transporter DMT1 was proposed as a mechanism by which HFE regulates iron absorption. To test this hypothesis, we investigated: (i) the effect of HFE antisense oligonucleotides on apical iron uptake by polarized Caco-2 cells; (ii) the apical/basolateral membrane distribution of HFE, beta-2 microglobulin and DMT1; (iii) the putative molecular association between HFE and DMT1. We found that HFE antisense treatment reduced HFE expression and increased apical iron uptake, whereas transfection with wild-type HFE inhibited iron uptake. Thus, an inverse relationship was established between HFE levels and apical iron uptake activity. Selective apical or basolateral biotinylation indicated preferential localization of DMT1 to the apical membrane and of HFE and beta-2 microglobulin (beta2m) to the basolateral membrane. Ectopic expression of HFE resulted in increased distribution of HFE-beta2m to the apical membrane. The amount of HFE-beta2m in the apical membrane inversely correlated with apical iron uptake rates. Immunoprecipitations of HFE or beta2m with specific antibodies resulted in the co-precipitation of DMT1. These results sustain a model by which direct interaction between DMT1 and HFE-beta2m in the apical membrane of Caco-2 cells result in down-regulation of apical iron uptake activity.


Frequency of daytime tooth clenching episodes in individuals affected by masticatory muscle pain and pain-free controls during standardized ability tasks.
Tooth clenching has been suggested to be related to temporomandibular pain. However, the electromyographic characteristics of daytime clenching episodes have been minimally investigated. This study aimed to analyze the frequency, amplitude, and duration of daytime clenching episodes in patients with masticatory muscle pain and pain-free individuals. Fifteen women with masticatory muscles myalgia (MP group, mean ± SD age = 26.4 ± 7.6 years) matched for age to 18 pain-free women (CTR group, mean ± SD age = 25.3 ± 2.8 years) were submitted to three different ability tasks (filling out questionnaires for 40 min, reading for 20 min, and playing a videogame for 20 min). The electromyographic activity periods (AP) of the right masseter greater than 10 % (AP10), 20 % (AP20), and 30 % (AP30) of the maximum voluntary contraction were analyzed. The mean frequencies of AP10, AP20, and AP30 were greater in MP than in CTR individuals (all p < 0.05). The mean duration of AP10 was higher in MP group than CTR group only while filling out the questionnaires (p = 0.0033). CTR group had an increased frequency and duration of AP10 while playing the videogame than while reading a magazine. The ability tasks did not affect the muscle activity in the MP group. Individuals with masticatory muscle pain have an increased frequency of both high and low-intense daytime clenching episodes. The type of ability task affects the frequency and the duration of clenching episodes only in pain-free individuals. Clinicians should recognize that the frequency and intensity of daytime clenching are noticeably increased in individuals with masticatory muscle pain in order to better tailor treatment.


Outcome of patients older than 85 years hospitalized in a neurology unit.
Advanced age is a major determinant of mortality and poor outcome at any level. In hospitalized patients, advanced age is a major issue in terms of prognosis, resource use, and therapeutic choices. We aimed at assessing the 1 year outcome of elderly patients admitted to a neurology unit for various acute conditions. Consecutive patients admitted to a neurology unit were enrolled and followed-up at 3, 6, and 12 months with structured phone interviews gathering information about mortality, disability, hospital readmissions, and place of residency. Inclusion criteria were age ≥ 85 years, availability of written consent and phone contact; no exclusion criteria were applied. Over a period of 16 months, 131 patients (88.8 ± 3.3, 92 females, 39 males) were admitted. The pre-hospitalization modified Rankin Scale (mRS) median (IQR) score, obtainable in 125 patients, was 2 (0, 3) and > 3 in 28/125 (22.4%) patients. Fifty-eight (46.8%) patients had pre-existing dementia (this information was missing for one patient). Eleven patients died during hospitalization. Of the 120 discharged patients, 60 (50%) were alive at 12 months, 41 died during follow-up (34.2%), and 19 (15.8%) were lost. At 12 months, out of the 60 alive patients, 29 (48.3%) had a mRS > 3. We did not detect predictors of 12-month survival. Predictors of 12-month worsening of functional status were pre-hospitalization mRS, pre-existing cognitive impairment, and male sex. One-year mortality of elderly patients admitted to a neurology unit is extremely high. After one year, less than one fourth of elderly patients hospitalised for an acute neurological disease are left with only no-to-moderate disability.


Incidence, Characteristics, and Cost of Eyelid Lacerations in the United States from 2006 to 2014.
To report the incidence, demographics, and cost of eyelid lacerations (ELs) in the USA. The Nationwide Emergency Department Sample is the largest publicly available emergency department database in the US. We conducted a retrospective longitudinal analysis to identify all emergency department (ED) visits in the sample from 2006 to 2014 with a primary or secondary diagnosis of EL. Descriptive statistics were calculated for hospital characteristics, patient demographics, and inflation-adjusted patient ED and in-patient (IP) charges. The incidence of primary and total ELs from 2006 to 2014 decreased by 50 per million and 7.1 per million, respectively. In the same period, the total ED and average ED charge, corrected for inflation, increased by almost $37 million and $1600 per person, respectively. Motor vehicle accidents (MVAs) were the mechanism of injury (MOI) associated with the highest average ED and IP costs at $5391 and $42,677, respectively. However, object- (42.2%) and fall-related (28.8%) were the most reported MOI overall. Peak months of EL presentations were seen in May and July, and > 90% of primary ELs were classified as periocular. Most ELs occurred in men and children, representing 69% and 44% of all primary EL cases, respectively. The incidence of ELs declined from 2006 to 2014. ELs occurred most frequently in children and young adults. The high proportion of object and fall-related injuries in this population highlights an area to develop strategies to reduce the frequency of preventable eye injuries.


Salt and mesophase formation in aqueous suspensions of lauric acid.
The solubility and solution behavior of lauric acid (LA) and its 1:1 acid soap (potassium hydrogen dilaurate) were investigated at 32 degrees C over a pH range of 2.5-8.5 and at varying KCl concentrations to examine the self-association of this long-chain carboxylic acid under these conditions. LA's solubility in water exhibited the classical pH dependence of a monocarboxylic acid with no evidence of self-association. In 0.1 M KCl between pH 6.3 and pH 7.3, filtered samples were turbid, suggesting the presence of high molecular weight aggregates (mesophase), which could be removed by ultrafiltration. The apparent LA solubility vs pH profile in ultrafiltered samples was consistent with a solid phase consisting of either the free acid (pH < 6.5) or potassium hydrogen dilaurate (pH > 6.5), again with no evidence of self-association to form low molecular weight species (dimers, etc.). Quasi-elastic light scattering (QLS) studies and mannitol trapping experiments indicated that vesicles were present in samples containing mesophase. The mesophase composition was characterized and a mass-action law for mesophase formation was developed to describe the apparent LA solubility versus pH in the mesophase region in terms of three parameters. The index of cooperativity, theta, indicated that the mesophase consists of approximately 25 molecules of LA with an acid:anion ratio, rho, of 1.7. The standard free energy of mesophase formation per mole of monomer was determined to be -6.3 kcal/mol. The aggregate size determined thermodynamically is several orders of magnitude less than that of the mesophase particle size determined by QLS measurements, suggesting that the LA monomer concentration in equilibrium with mesophase may be governed by a small unit domain of the vesicle. These observations may have a bearing on the thermodynamics of self-assembly of lipid bilayer membranes.


An expanded and flexible form of the vacuolar ATPase membrane sector.
The vacuolar ATPase integral membrane c-ring from Nephrops norvegicus occurs in paired complexes in a double membrane. Using cryo-electron microscopy and single particle image processing of 2D crystals, we have obtained a projection structure of the c-ring of N. norvegicus. The c-ring was found to be very flexible, most likely as a result of an expanded conformation of the c subunits. This structure may support a role for the vacuolar ATPase c-rings in membrane fusion.


Detection of colipase in serum and urine of pancreatitis patients.
Colipase, like other pancreatic proteins, is liberated into the circulation in acute pancreatitis. Its concentration was measured in serum by a turbidimetric and in urine by a titrimetric method. The principle of both assays is based on the reactivation of bile acid inhibited, pure human pancreatic lipase by colipase. Whereas in healthy individuals colipase was found neither in serum nor urine (detection limit approximately 6.5 micrograms/1), a wide concentration range was observed in 29 patients with acute pancreatitis. Urine values varied between 3.8 and 7121 micrograms colipase/g creatinine; in serum levels up to 664 micrograms/1 were found. There was no correlation with serum lipase activity: On a molar basis, the ratio of serum colipase to serum lipase ranged between less than 0.04 and 2.14, but was below 1 in most sera. Colipase is rapidly removed from the circulation by glomerular filtration, its elimination rate from serum being more than twice as fast as that of lipase. This results in a constant decrease of the colipase/lipase ratio during the course of the disease. Probably determination of colipase is of no direct diagnostic value in pancreatic disorders, but our findings are of considerable significance for the measurement of serum lipase in the presence of bile acids, particularly with regard to turbidimetric assays. We conclude that lipase activity values obtained by these methods are mainly dependent on the degree of saturation of the enzyme with its cofactor and not on the true lipase concentration.


An orderly sequence of autonomic and neural events at transient arousal changes.
Resting-state functional magnetic resonance imaging (rsfMRI) allows the study of functional brain connectivity based on spatially structured variations in neuronal activity. Proper evaluation of connectivity requires removal of non-neural contributions to the fMRI signal, in particular hemodynamic changes associated with autonomic variability. Regression analysis based on autonomic indicator signals has been used for this purpose, but may be inadequate if neuronal and autonomic activities covary. To investigate this potential co-variation, we performed rsfMRI experiments while concurrently acquiring electroencephalography (EEG) and autonomic indicator signals, including heart rate, respiratory depth, and peripheral vascular tone. We identified a recurrent and systematic spatiotemporal pattern of fMRI (named as fMRI cascade), which features brief signal reductions in salience and default-mode networks and the thalamus, followed by a biphasic global change with a sensory-motor dominance. This fMRI cascade, which was mostly observed during eyes-closed condition, was accompanied by large EEG and autonomic changes indicative of arousal modulations. Importantly, the removal of the fMRI cascade dynamics from rsfMRI diminished its correlations with various signals. These results suggest that the rsfMRI correlations with various physiological and neural signals are not independent but arise, at least partly, from the fMRI cascades and associated neural and physiological changes at arousal modulations.


Total neoadjuvant therapy versus standard therapy in locally advanced rectal cancer: A systematic review and meta-analysis of 15 trials.
Neoadjuvant chemoradiotherapy (nCRT) before total mesorectal excision (TME) and followed systemic chemotherapy is widely accepted as the standard therapy for locally advanced rectal cancer (LARC). This meta-analysis was to evaluate the current evidence regarding nCRT in combination with induction or consolidation chemotherapy for rectal cancer in terms of oncological outcomes. A systematic search of medical databases (PubMed, EMBASE and Cochrane Library) was conducted up to the end of July 1, 2021. This meta-analysis was performed to evaluate the efficacy of TNT in terms of pathological complete remission (pCR), nCRT or surgical complications, R0 resection, local recurrence, distant metastasis, disease-free survival (DFS) and overall survival (OS) in LARC. Eight nRCTs and 7 RCTs, including 3579 patients were included in the meta-analysis. The rate of pCR was significantly higher in the TNT group than in the nCRT group, (OR 1.85, 95% CI 1.39-2.46, p < 0.0001), DFS (HR 0.80, 95% CI 0.69-0.92, p = 0.001), OS (HR 0.75, 95% CI 0.62-0.89, p = 0.002), nCRT complications (OR 1.05, 95% CI 0.77-1.44, p = 0.75), surgical complications (OR 1.02, 95% CI 0.83-1.26, p = 0.83), local recurrence (OR 1.82, 95% CI 0.95-3.49, p = 0.07), distant metastasis (OR 0.77, 95% CI 0.58-1.03, p = 0.08) did not differ significantly between the TNT and nCRT groups. TNT appears to have advantages over standard therapy for LARC in terms of pCR, R0 resection, DFS, and OS, with comparable nCRT and postoperative complications, and no increase in local recurrence and distant metastasis.


Participant-Directed Intervention Tailoring Is Associated With Improvements in Glycemic Control for South Asian Adults With Type 2 Diabetes.
Our aim was to determine the impact of a 3-month diabetes self-management education and support (DSME/DSMS) intervention involving both professional and peer support on glycemic control and diabetes distress in South Asian adults with type 2 diabetes (T2D) living in Metro Vancouver. We recruited 114 South Asian adults with T2D for a study conducted across 7 sites in Metro Vancouver. A previous DSME/DSMS intervention was modified using participant feedback. Participants attended the updated intervention involving 6 biweekly group-based DSME sessions co-led by a diabetes educator and peer leader and 6 biweekly DSMS sessions delivered by a peer leader. Assessments were conducted at baseline and 3 months. Primary outcomes were glycated hemoglobin (A1C) and diabetes distress. Secondary outcomes included apolipoprotein B, blood pressure (BP), height and weight, waist circumference, diabetes support and depressive symptoms. After the 3-month intervention, linear mixed-effects modelling demonstrated A1C decreased significantly from 8.2% (66 mmol/mol) to 7.8% (62 mmol/mol) (p<0.0001), as did body mass index (from 30.02 to 29.7 kg/m2; p=0.0005) and diastolic BP (from 75.86 to 70.78 mmHg; p<0.0001). These reductions persisted after adjusting for the fixed-effects of age, sex, intensification of diabetes and BP medication, as well as random effects for subject and location. Participation in a professional plus peer-led intervention tailored by South Asian adults with T2D is associated with improved glycemic control and other favourable health outcomes.


Character strengths: a study of Argentinean soldiers.
The primary objective of this research was to study the differences in positive traits between military and civilian college students and between cadets in their first and final years at a military academy. Second, the research aimed to study the relations between positive traits and the academic and military performance of cadets in their first and final years, according to the classification of positive traits by Peterson and Seligman (2004). To accomplish these objectives, a sample of university students from a military educational institution and a sample of civilian university students were studied. The instruments used were a 24-item self-report measure of positive traits, a measure of social desirability, and objective scores of academic and military performance. The results generally showed that when age and career stage were held constant, the scores of the military students were higher than the scores of the civilian students across various strengths. Military students reported higher levels of the character strength of spirituality than did civilian students. The relationships between strengths and performance differed for students in their first and final years at the military academy. In particular, cadets with the higher levels of academic or military performance in their last year, i.e., the cadets best adapted to the academy, reported higher levels of the character strength of persistence when compared to low-performing cadets in the same year of study.


Ion-molecule condensation reactions: a mechanism for organic synthesis in ionized reducing atmospheres.
The CH3+ ion, formed in ionized methane, undergoes consecutive eliminative condensation reactions with methane to form the carbonium ions C2H5+, i-C3H7+ and t-C4H9+. At T smaller than 500 degrees K, NCH4 greater than 10(16) cm-3 these ions react with NH3 in competitive condensation -- H+ transfer reactions, e.g. C2H5 + NH3 M leads to C2H5NH3+ leads to NH4+ + C2H4 At particle densities of NCH4 smaller than 10(16) cm-3 proton transfer is the only significant reaction channel. At NCH4 greater than 10(17) cm-3 condensation constitutes 5--20% of the overall reactions. The product of the condensation reaction further associates with CO2 to form C2H5NH3+ . CO2; the atomic composition of this cluster ion is identical with the protonated amino acid alanine. The carbonium ions i-C3H7+ and t-C4H9+ condense also with HCN to yield protonated isocyanides. HCNH% also appears to condense with HCN at T greater than 570 degrees K, and form cluster ions with HCN at lower temperatures. The rate constants of the condensation reactions vary with temperature and pressure in a complex manner. Under conditions similar to those on Titan at an altitude of 100 km (T = 100--150 degrees K, NCH4 approximately 10(18) cm-3), with a methane atmosphere containing 1% H2 and traces of NH3 and H2O, ion-molecule condensation reactions followed by H+ transfer are expected to lead to the atmospheric synthesis of C2H6, C3H8, CH3OH, C2H5OH and the terminal ions NH4+, CH3NH3+ and C2H5NH3+. At higher temperatures (250 degrees K smaller than T smaller than 400 degrees K), the synthesis of i-C4H10, i-C3H7OH and t-C4H9OH and of the ions i-C3H7NH3+ and t-C4H9NH3+ is also expected. Electron recombination of the terminal ions may yield amines, imines and nitriles. Cycles of protonation and dissociative recombination of the alkanes and alcohols produced in condensation reactions will also produce unsaturated hydrocarbons, ketones and aldehydes in the ionized atmosphere.


The mediation of macrophage reaction in inflammation, with special reference to IgG-derived chemotactic factor.
Three different macrophage chemotactic factors were separated from hypersensitivity skin lesions induced by DNP-ascaris extract or PPD. The amount of each factor seemed to be changeable according to the nature of inflammatory stimuli. The chemotactic activity of the factor a was completely absorbed by anti-IgG and anti-light chain antibodies, while that of the factors b and c was not absorbed by the antibodies. The factor a was produced from IgG by neutrophil neutral serine protease resembling elastase but failing to digest elastin-orcein; its chemotactic generation was accompanied by release of dialysable peptide(s) from the IgG molecule, suggesting a minor structural change of the IgG molecule. Production of leucoegresin or lymphocyte chemotactic factor by neutrophil neutral thiol protease from IgG molecule was discussed.


Determinants of Access to Essential Surgery in the Democratic Republic of Congo.
In the Democratic Republic of Congo (DRC), the determinants and barriers of essential surgical care are not well described, hindering efforts to improve national surgical programs and access. A cross-sectional study evaluated access to essential surgery in the Butembo and Katwa health zones in the North Kivu province of DRC. A double-clustered random sample of community members was surveyed using questions derived from the Surgeons OverSeas Surgical Needs Assessment Survey, a validated tool to determine the reasons for not seeking, reaching, or receiving a Bellwether surgery (i.e., caesarean delivery, laparotomy, and external fixation of a fracture) when needed. Overall, 887 households comprising 5944 community members were surveyed from April to August 2022. Six percent (n = 363/5944) of the study population involving 35% (n = 309/887) households needed a Bellwether surgery in the previous year, 30% (n = 108/363) of whom died. Of those who needed surgery, 25% (n = 78) did not go to the hospital to seek care and were more likely to find transportation unaffordable (P = 0.042). The most common reasons for not seeking care were lack of funds for hospitalization, prior poor hospital experience, and fear of hospital care. Access and delivery of essential surgery are drastically limited in the North Kivu province of the DRC, such that a quarter of households needing surgery fails to seek surgical care. Poor access was predominantly driven by households' inability to pay for surgery and community distrust of the hospital system.


Evaluation of 2-deoxy-2-[18F]fluoro glucaric acid (FGA) as a potential PET tracer for tumor necrosis.
In this study, [18F]FGA was obtained by a one-step oxidation of [18F]FDG using sodium hypochlorite. The conversion from [18F]FDG to [18F]FGA was confirmed by HPLC to be over 95% using the optimal condition. A549-luciferase NSCLC xenografted mice was used for in vivo PET imaging. Prior to either saline or cisplatin treatment, there was no significant difference on tumor uptake of [18F]FGA in all mice, with an average uptake of (0.21 ± 0.16) %ID/g. After treatment, tumor uptake of [18F]FGA was not changed significantly for saline-treated mice, whereas the tumor uptake of [18F]FGA drastically increased for cisplatin-treated mice, with an average uptake of (1.63 ± 0.16) %ID/g. The ratio of tumor uptake between cisplatin-treated vs. saline-treated mice was 7.8 ± 0.2 within one week of treatment. PET imaging results were consistent with ex vivo biodistribution data. BLI showed significant light intensity suppression after treatment, indicating necrosis. Our data indicate that [18F]FGA uptake was related to tumor necrosis. [18F]FGA PET/CT imaging might be a useful tool to monitor treatment response to chemotherapy by imaging tumor necrosis.


Chronic pain, healthcare utilization, and quality of life following gastrointestinal surgery.
Our aim in this pilot study was to identify potential predictors of chronic post-surgical pain (CPSP) and other outcomes to consider for inclusion in future prospective studies of CPSP following abdominal gastrointestinal surgery. We followed 76 surgical patients during this prospective single-centre cohort study. Pain characteristics, health-related quality of life (HRQOL), and healthcare utilization were assessed preoperatively, at six weeks postoperatively, and at six months postoperatively. Statistical analyses included descriptive statistics and repeated measures analysis of variance. Prior to surgery, 42% of patients reported no pain, 18% reported remote pain, and 33% reported pain at the surgical site. Six months after surgery, 29% of patients with preoperative remote pain and 35% of patients with preoperative pain at the surgical site reported CPSP. Pain-related interference declined from the preoperative to postoperative period; however, six months after surgery almost one-third of participants continued to report pain-related interference with mood (28%), sleep (30%), and enjoyment of life (30%). Consistent with studies of other surgical procedures, measures of anxiety and depression were associated with an increased risk of CPSP. During the six months following surgery, 12% of patients visited the Emergency Department, 15% visited non-traditional providers, and 9.2% visited a walk-in clinic for pain. Compared with Canadian norms, HRQOL was poorer in all domains preoperatively, in all domains but mental health six weeks postoperatively, and in most domains six months postoperatively. This feasibility study provides a template for future studies of CPSP following gastrointestinal surgery. Results suggest a substantial burden of persistent pain, healthcare utilization, and decreased HRQOL. Larger-scale studies that are similarly designed will serve to identify predictors of CPSP in this surgical population.


Syntheses of 1-deoxy-3-s-(1-thio-alpha-D-glucopyranosyl)-mannojirimycin and 1-deoxy-3-O-(5-thio-alpha-D-glucopyranosyl)-mannojirimycin as potential inhibitors of endo-alpha-D-mannosidase.
1-Deoxy-3-S-(1-thio-alpha-D-glucopyranosyl)-mannojirimycin and 1-deoxy-3-O-(5-thio-alpha-D-glucopyranosyl) mannojirimycin were chemically synthesized as potential inhibitors of endo-alpha-D-mannosidase.


Schistosoma mansoni: biochemical characteristics of the antischistosomal effects of Ro 15-5458.
We evaluated a variety of biochemical parameters in Schistosoma mansoni isolated from mice up to 4 days after dosing with 15 mg/kg Ro 15-5458. While no drug effect could be demonstrated in the utilization of media glucose, glycogen content, gut pigment, or ATP levels of the parasites, a significant reduction (P less than or equal to 0.05) in parasite weight and protein content was observed. Possible drug actions that may contribute to the loss in parasite protein and perhaps ultimately result in parasite death have been investigated. We noted significant reduction in the incorporation of leucine and thymidine into acid-insoluble fractions of the parasites. The reduction in the incorporation of leucine into parasite proteins was nonspecific and preceded the effect of the drug on the uptake of the amino acid. Parasite and host liver RNA isolated after dosing were translated in vitro in a rabbit reticulocyte system. Drug-treated parasite mRNA, but not that of the host, was less effective than control mRNA in directing the incorporation of [35S]methionine. We propose a hypothesis that attributes the loss in protein content to a defect in the biosynthesis of parasite proteins as a result of a drug-induced reduction in the quantity of mRNA in the parasites This effect of Ro 15-5458 on the parasite may provide the basis for its schistosomicidal action.


Effectiveness of Family-Focused Nurse-led Intervention on Functional Improvement of Patients with Bipolar Disorder at a Tertiary Hospital in South India: A Randomized Controlled Trial.
Bipolar affective disorder (BPAD) is a chronic, episodic illness that can create problems and disruptions in the social, occupational, and family functioning of a client. Families are frequently most affected by their bipolar member and have a sense of helplessness to fix bipolar symptoms. The current study aimed to assess the effectiveness of Family-focused Nursing Interventions (FFNI) on functional improvement in the sample of symptomatic bipolar affective disorder clients. In this experimental study, 149 patients with BPAD were interviewed along with family members through the consecutive sampling technique from the inpatient ward. Varying block randomization was used to allocate the patients to the control and experimental groups. After obtaining ethical clearance, the study was registered under the Clinical trail registry India (CTRI). Baseline sociodemographic and clinical variables, and the functional levels, were assessed using Longitudinal Interval Follow-up Evaluation-Range of Impaired Functioning Tool and Functional Assessment Short Test. The control group (74) received routine treatment; the experimental group (75) received routine treatment along with FFNI in seven sessions, and posttest was conducted at discharge, one-month, and at two-month follow-up at OPD. The collected data were analyzed using SPSS 20 (IBM Corp. Released 2011. IBM SPSS Statistics for Windows Version 20.0, Armonk, NY: IBM Corp.), independent sample t-test, analysis of variance, and Pearson correlation used. A P-value of less than 0.05 was considered as a statistically significant result. At the end of the study, 149 clients completed the treatment and follow-up. Both the groups were comparable at baseline in demography as well as clinical variables. There was significant improvement in the functional level after FFNI. The total score of LIFE-RIFT and the Functional Assessment Short Test score were significantly lower in the experimental group than the control group with P = 0.001. The current study concluded that adjuvant to routine treatment FFNI will improve the functional ability of the client along with routine psychiatric treatment for BPAD.


Regulation of experimental allergic encephalomyelitis. Part 4. Further characterization of postrecovery suppressor cells.
Suppressor cells that regulate experimental allergic encephalomyelitis (EAE) are present in lymph nodes of Lewis rats that have recovered from the disease, as demonstrated by adoptive transfer of suppression for at least 108 days following challenge of donor rats with myelin basic protein (BP) in complete Freund's adjuvant (CFA). These suppressor lymph node cells (LNC) inhibit the occurrence of active, but not passive EAE in recipients, suggesting that they function early in the inductive phase of the response to BP. The suppressor cells are nylon-adherent, and suppression can be partially abrogated by depletion of B cells with anti-immunoglobulin (ig) and complement (C). Serum from recovered donors has, at best, only a modest suppressive effect when transfused into syngeneic recipients. These findings suggest that the B cells do not mediate suppression on EAE via production of blocking antibody, but may function directly, perhaps by triggering T cells to become suppressor cells.


[MRI features of phyllodes tumor of the breast and the pathological study].
To analyze the features of MRI and pathology for phyllodes tumor of the breast and to improve the diagnosis level. The MRI data of 11 patients with phyllodes tumor of the breast were analyzed. The MRI features included morphology, signal intensity on pre-enhanced T1WI, appearance of dynamic contrast enhancement (DCE-MRI) and the type of time-signal intensity curve (TIC). The pathologic diagnosis for the 11 phyllodes tumor included 6 benign, 2 borderline and 3 malignant. All of the 11 tumors showed well-defined margins and lobulated lump. The signal intensity of tumor was lower (4 cases) than or equal (7 cases) to that of normal breast tissue on T1-weighted images. On T2-weighted images, 5 cases presented variegated appearance, 6 cases displayed high signal. Four cases showed patchy high signal on T1WI and T2WI. All patients underwent DCE-MRI and showed uneven enhancement. There were 7 cases in type I of TIC and 4 cases in type II. The imaging findings of phyllodes tumor on MR is characteristic but not specific, the final diagnosis still depends on the histopathologic examination.


Inhibition by fatty acids during fermentation of pre-treated waste activated sludge.
Fermentation of waste activated sludge produces volatile fatty acids (VFAs), which can be used as the carbon sources for numerous biological processes. However, product inhibition can limit extent of fermentation to VFAs. In this study, product inhibition during fermentation of waste activated sludge pre-treated by a thermal hydrolysis process (THP-WAS) was investigated. Product inhibition was confirmed as spiking reactors with high levels of a mix of VFAs prevented fermentation taking place. Various inhibition models were trialled and it was found that a threshold model (based on thermodynamics) provided the best fit between model and data. This is the first time that threshold type inhibition has been shown for a mixed substrate, mixed population system. Batch fermentations carried out with THP-WAS of different dilutions were used to evaluate the impact of different organic loadings. The threshold VFA concentration for the systems studied was determined to be 17±1gCOD(VFA)L(-1). Inhibition was shown to be due to the presence of a combination of VFAs containing 2-6 carbon atoms each. When evaluated individually, by spiking individual VFAs, all VFAs except for acetate had the same impact at this threshold; acetate being approximately 50% as inhibitory as the other organic acids (COD basis). Based on this, a weighted model could be proposed to better represent the data. Strategies to improve overall yield could be increased production of acetate, or dilution to below the inhibitory level.


The use of 3'-deoxy-3'-18F-fluorothymidine (FLT) PET in the assessment of long-term survival in breast cancer patients treated with neoadjuvant chemotherapy.
To assess the role of serial FLT-PET scans during early neoadjuvant treatment as a prognostic marker of response to treatment and survival. This study is a prospective cohort study which draws from a larger original study which examined the utility of FLT-PET imaging across multiple cancers. Our cohort consisted of patients who had biopsy-confirmed breast cancer amenable to surgical resection. These patients underwent serial FLT-PET scans: the first scan prior to starting neoadjuvant chemotherapy (NAC), and a second scan shortly after starting NAC. SUVmean was derived using an isocontour ROI drawn approximately half way between the SUVmax and background on three planes for each scan. The change in mean standardized uptake value (SUVmean) for the primary tumor between these two scans was then calculated, and patients were stratified into "responder" and "non-responder" groups based on a cut-off of 20% arithmetic decrease in SUVmean between the two scans. The rates of pathologic complete response (pCR) on subsequent surgical excision, overall survival (OS), and progression-free survival (PFS) were then compared between the two groups to assess for significant difference between responders and non-responders. 16 patients (n = 16) met criteria for inclusion and successfully underwent FLT-PET scans in the prescribed sequence of events. Seven of these patients had a decrease of 20% or larger between the two serial PET scans, making them "responders". The remaining nine patients were "non-responders" to NAC based on PET imaging. Between responders and non-responders, there was no significant difference in median PFS (7.9 years versus 3.7 years; p = 0.425) and median OS (7.5 years versus 5.0 years; p = 0.944). In the 14 patients who underwent surgical resection (n = 14), there was no significant difference in the rate of achieving pCR (33% vs. 14%; p = 0.5846) between responders and non-responders. Further study of a larger sample size is needed to examine the potential role for FLT-PET in predicting response to neoadjuvant treatment, particularly in correlating with long-term overall and progression-free survival. Our study is limited by small sample size, but does suggest that FLT-PET has a role in the long-term prognosis of breast cancer treated with NAC and surgical resection which is worthy of further study.


Insular biogeography of the montane butterfly faunas in the Great Basin: comparison with birds and mammals.
Butterfly species lists were assembled for 18 Great Basin mountain ranges for which distributional data on mammals and birds have been analysed previously by other workers. The ranges represent remnant islands of the boreal habitat that once was continuous across the Great Basin but is now restricted to higher elevations as a result of climatic change at the close of the Pleistocene. The effects of biogeographic factors (area, distance, elevation) and habitat diversity on butterfly species number were examined. The Great Basin boreal butterfly faunas were found to be depauperate overall relative that of the principal mainland source, the Rocky Mountains, and were found to have fewer species than predicted by the mainland species-area data. However, only a weak area effect, and no distance effect, was detected by bivariate and multivariate analysis. Furthermore, the habitat diversity score found to explain virtually all the variation in bird species number in the same ranges in previous studies is only marginally significantly correlated with butterflies. When the butterflies are subdivided according to their vagility, the relative differences in the species-area correlation and slope (z-value) between the vagility categories were consistent with those found previously for mammals and birds, and, as predicted by theory, less vagile taxa exhibit higher species-area correlations and z-values. Overall, differences in the insular biogeography of buttterflies and vertebrates seem to reflect fundamental ecological differences between the taxa.


The cost of a single concussion in American high school football: a retrospective cohort study.
The potential financial burden of American football-related concussions (FRC) is unknown. Our objective was to describe the healthcare costs associated with an FRC and determine factors associated with increased costs. A retrospective cohort study of concussed high school football players presenting between November 2017 and March 2020 was undertaken; 144 male high school football players were included. Total costs were about $115,000, for an average direct healthcare cost of $800.10/concussion. Visiting the emergency department (β = 502.29, 95% CI: 105.79-898.61; p = 0.01), the initial post-concussion symptom scale score (β = 0.39, 95% CI: 0.11-0.66; p = 0.01) and a post-concussion syndrome diagnosis (β = 670.37, 95% CI: 98.96-1241.79; p = 0.02) were each independently associated with total costs. A granular understanding of cost-driving factors associated with FRC is the first step in understanding the cost-effectiveness of prevention and treatment methods.


Oscillatory potentials of the electroretinogram in hypertensive patients with different antihypertensive treatment.
Oscillatory potentials of the electroretinogram are useful to confirm the diagnosis of essential hypertension. Thirty-five hypertensive patients underwent primary antihypertensive therapy with four different treatments. Oscillatory potentials were recorded before the treatment and after 12 months. The oscillatory response increased in a statistically significant manner in the angiotensin-converting enzyme inhibitor group. This is probably caused by the vasodilatation mechanism, which increases the retinal blood flow.


Five-year clinical performance of a HEMA-free one-step self-etch adhesive in noncarious cervical lesions.
The objective of this randomized controlled trial was to evaluate the clinical performance of a 2-hydroxyethyl methacrylate (HEMA)-free one-step adhesive. Two hundred sixty-seven cervical lesions in 52 patients were restored with the composite Gradia Direct (GC), bonded with either the one-step self-etch adhesive G-Bond (GC) or the three-step etch-and-rinse adhesive Optibond FL (Kerr) in a random order. The restorations were evaluated for retention, marginal integrity, marginal discoloration, and caries occurrence after 5 years. Specific statistics were used to account for the clustered data (multiple restorations per patient). The clinical success rate for G-Bond (87.4 %) was not significantly different from that of Optibond FL (90.9 %). Both adhesives showed progressive marginal deterioration, but G-Bond exhibited more small enamel defects and marginal discoloration, and unlike previous recalls, several restorations failed because of deep microleakage. Large sclerotic lesions were a significant risk factor for retention loss with G-Bond. Irrespective of the adhesive, almost all restorations with retention loss were located in the lower jaw. After 5 years of clinical service, restorations bonded with the HEMA-free one-step adhesive did not need repair or replacement more often than those with the three-step etch-and-rinse adhesive, and both adhesives had a high retention rate (>90 %). There were indications that G-Bond did not (self-)etch enough in some clinical situations, as G-Bond exhibited more incisal defects and marginal discolorations, and sclerotic lesions were at higher risk of retention loss. The clinical performance of the HEMA-free one-step adhesive was clinically acceptable after 5 years.


Neurofibromatosis and Attentional Deficits: An Illustrative Example of the Common Association of Medical Causes with Behavioural Syndromes, Implications for General Child Mental Health Services.
Neurofibromatosis type 1 (NF1) is a common autosomal dominant gene disorder. In addition to well described physical and cognitive features certain behavioural patterns have been reported. Clear association has been shown between NF1 and attention deficit hyperactivity disorder (ADHD), with up to half of children with NF1 fulfilling DSM-IV diagnostic criteria for ADHD. This article aims to increase awareness among child mental health workers of the common link between genetic conditions (like NF1) and ADHD, thus improving diagnosis and intervention.


[Effect of compound recipe Gengniankang on senile sexual hormone and expression of estrogen receptor in bone of climacteric female rats].
To compare the therapeutic effect of Compound Recipe Gengniankang ( GNK) with that of hormone replacement treatment (HRT) on climacteric female rats with osteoporosis, and to investigate the roles of estrogen and estrogen receptors in the mechanism of osteoporosis. Climacteric female rats with osteoporosis were chosen and divided into three groups (GNK group, HRT group and control group). Apoptosis of ovarian granulose cells was measured by terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) assay. Serum level of estradiol (E(2)), follicle stimulating hormone (FSH), luteinizing hormone (LH) were determined by the method of radioimmunoassay (RIA). Reverse transcriptase polymerase chain reaction (RT-PCT) technology was used to evaluate the expression of estrogen receptor (ER) in bone. Bone mineral density (BMD) was measured by double energy X-ray absorption (DEXA). In the climacteric rats, BMD, serum E(2), ER mRNA expression in bone decreased remarkably, and serum FSH, LH and apoptosis of ovarian granulose cells increased obviously. After treating with GNK, all the indexes were reversed except serum E(2). The increase of E(2) was not significant. GNK is effective on climacteric osteoporosis female rats. Its role is performed not by increasing serum E(2) but by enhancing ER in the bone and inhibiting apoptosis of ovarian granulose cells. GNK can deter further exhaustion of ovarian function.


U2 RNA shares a structural domain with U1, U4, and U5 RNAs.
We previously reported common structural features within the 3'-terminal regions of U1, U4, and U5 RNAs. To check whether these features also exist in U2 RNA, the primary and secondary structures of the 3'-terminal regions of chicken, pheasant, and rat U2 RNAs were examined. Whereas no difference was observed between pheasant and chicken, the chicken and rat sequences were only 82.5% homologous. Such divergence allowed us to propose a unique model of secondary structure based on maximum base-pairing and secondary structure conservation. The same model was obtained from the results of limited digestion of U2 RNA with various nucleases. Comparison of this structure with those of U1, U4, and U5 RNAs shows that the four RNAs share a common structure designated as domain A, and consisting of a free single-stranded region with the sequence Pu-A-(U)n-G-Pup flanked by two hairpins. The hairpin on the 3' side is very stable and has the sequence Py-N-Py-Gp in the loop. The presence of this common domain is discussed in connection with relationships among U RNAs and common protein binding sites.


Comparison of influenza A and influenza B virus infection in hospitalized children.
Influenza A and B viruses were cocirculating in Australia in the winter of 1997. To compare the clinical and demographic features of children with influenza A or influenza B virus infection admitted to a paediatric tertiary referral centre. Retrospective chart review of 91 hospitalized children with culture-proven influenza A or B virus infection during 1997. Thirty-six (56%) of 64 children with influenza A were under 12 months of age compared with seven (26%) of 27 children with influenza B virus infection (P = 0.02). Influenza B virus infection was more common in children with underlying medical problems (P = 0. 01). Neurological manifestations were present in eight (12.5%) of 64 children with influenza A and none with influenza B virus infection (P = 0.09). There were no significant differences in signs and symptoms of children with influenza A and B virus infection, in severity of illness or in duration of hospital stay. A greater proportion of children admitted with influenza A virus infection were under 12 months of age. Influenza B virus infection is associated more commonly with underlying medical disorders. It is not possible to differentiate between influenza A or B virus infection from presenting clinical signs and symptoms.


Techniques for Catheter Ablation of Idiopathic Ventricular Arrhythmias Originating from the Outflow Tract and Left Ventricular Summit.
Idiopathic ventricular arrhythmias (VAs) most commonly originate from the ventricular outflow tracts. Because the anatomy of this region is complex and some of those VA origins are intramural and epicardial, it may sometimes be difficult to locate the site of the VA origin. Meticulous mapping in multiple different locations such as the right and left ventricular outflow tracts, endocardial and epicardial sites, and above and below the aortic and pulmonic valves may be required to achieve successful catheter ablation of those VAs. Special ablation techniques may be considered to improve the outcome of catheter ablation of intramural and epicardial VAs.


Altered emotion regulation in obsessive-compulsive disorder as evidenced by the late positive potential.
Obsessive-compulsive disorder (OCD) is associated with marked anxiety, which triggers repetitive behaviours or mental rituals. The persistence of pathological anxiety and maladaptive strategies to reduce anxiety point to altered emotion regulation. The late positive potential (LPP) is an event-related brain potential (ERP) that reflects sustained attention to emotional stimuli and is sensitive to emotion-regulation instructions. We hypothesized that patients with OCD show altered electrocortical responses during reappraisal of stimuli triggering their symptoms. To test our hypothesis, ERPs to disorder-relevant, generally aversive and neutral pictures were recorded while participants were instructed to either maintain or reduce emotional responding using cognitive distraction or cognitive reappraisal. Relative to healthy controls, patients with OCD showed enhanced LPPs in response to disorder-relevant pictures, indicating their prioritized processing. While both distraction and reappraisal successfully reduced the LPP in healthy controls, patients with OCD failed to show corresponding LPP modulation during cognitive reappraisal despite successfully reduced subjective arousal ratings. The results point to sustained attention towards emotional stimuli during cognitive reappraisal in OCD and suggest that abnormal emotion regulation should be integrated in models of OCD.


Case report: Efficacy analysis of radiofrequency catheter ablation combined with atrial appendage resection for atrial tachycardia originating from the atrial appendage in children.
The aim of this study was to investigate the efficacy of radiofrequency catheter ablation (RFCA) combined with atrial appendage (AA) resection to treat atrial tachycardia (AT) originating from the AA in children. Using the Ensite three-dimensional electroanatomic mapping system, three children with AT originating from the AA were diagnosed. Clinical features and electrocardiographic (ECG) manifestations were analyzed. Ablations were performed using a cold saline-infused catheter at appendages targeting loci of AT origin under the guidance of the Ensite system. Atrial appendage resection was performed in combination with cardiac surgery, and the curative effect was evaluated. The ages of the three patients were 3.5, 5.75, and 12.9 years. Two cases originated from the right atrial appendage (RAA) and one originated from the left atrial appendage (LAA). The ECG characteristics of AT from the RAA were as follows: (1) negative P waves in lead V1; (2) positive P waves in leads II, III, and aVF; (3) positive P wave in lead I with varying shapes in lead aVL; and (4) prolonged PR interval with no QRS wave after some P waves. The ECG of the LAA was characterized by (1) positive P waves in lead V1 with a bimodal pattern; (2) positive P waves in leads II, III, and aVF; and (3) negative P waves in leads I and aVL. Preoperative echocardiography showed cardiac enlargement and a decreased left ventricular ejection fraction (LVEF) in all three cases. One case was cured after RFCA, and the remaining two cases required AA resection after RFCA. No recurrence was detected at 1-18 months of follow-up, and the left ventricular end-diastolic diameter and LVEF returned to normal. Atrial tachycardia originating from the AA in children showed a characteristic P-wave presentation on ECG, and sustained episodes of AT resulted in tachycardia-induced cardiomyopathy. Children who are not successfully controlled by RFCA or who have a recurrence after RFCA could benefit from AA resection.


Laryngomalacia induced by exercise in a pediatric patient.
Exercise-induced laryngomalacia (EIL) is characterized by inspiratory stridor that is brought on by exercise (i.e. competitive sports) and fails to respond to treatment with bronchodilators (Smith et al., Ann Otol Rhinol Laryngol 1995;104:537-541). During exercise, (1) spirometric flow volume loops show evidence of variable extrathoracic obstruction, and (2) laryngoscopy shows inspiratory prolapse of supraglottic structures with partial glottic obstruction. Only five cases of probable EIL have been reported in the literature (Smith et al., Ann Otol Rhinol Laryngol 1995;104:537-541; Lakin et al., Chest 1984;86:499-501; Bittleman et al., Chest 1994;106:615-616; Bent et al., Ann Otol Rhinol Laryngol 1996;105:169-175; Chemery et al., Rev Mal Respir 2002;19:641-643). Here, a case of laryngomalacia induced by exercise in a previously asymptomatic 10-year-old athlete with a remote history of laryngomalacia in infancy is presented, and a review of previously reported cases is provided.


Effect of ionic environment on densities of membrane-associated particles in presynaptic membranes observed in freeze-fractured synaptosomes.
The effects of high-K and high-Ca in the incubation medium on membrane-associated particles of the presynaptic membranes were examined. There was a marked increase in the density of protoplasmic fracture face after incubation in the high-K or high-Ca medium.


Brain tissue volume measurement from magnetic resonance imaging. A phantom study.
The authors appraised the accuracy of a method for brain volume measurement from magnetic resonance images and evaluated the effects of the acquisition matrix, slice thickness, and tissue sampling on the measurement error. The method uses two magnetic resonance imaging sequences to account explicitly for partial volume effects. The accuracy was measured with one-, two-, and three-compartmental phantoms that mimic the relaxation properties of brain tissues. The sensitivity of the method to section thickness was measured by repeated scans of human brain. Using a strongly T2-weighted sequence and two-compartmental phantoms, the average error was 5%, with 3% error for phantoms larger than 90 mL. In the three-compartmental phantoms the error varied from 2% to 7%. Varying the section thickness from 5 to 10 mm on three-compartmental phantoms and from 2.5 to 10 mm in the human brain did not significantly affect compartmental volumes. The experimental study validates the feasibility of monitoring localized volume changes in a three-compartmental model.


Contingent versus routine third-trimester screening for late fetal growth restriction.
To evaluate the use of third-trimester ultrasound screening for late fetal growth restriction (FGR) on a contingent basis, according to risk accrued in the second trimester, in an unselected population. Maternal characteristics, fetal biometry and second-trimester uterine artery (UtA) Doppler were included in logistic regression analysis to estimate risk for late FGR (birth weight < 3(rd) percentile, or 3(rd) -10(th) percentile plus abnormal cerebroplacental ratio or UtA Doppler, with delivery ≥ 34 weeks). Based on the second-trimester risk, strategies for performing contingent third-trimester ultrasound examinations in 10%, 25% or 50% of the cohort were tested against a strategy of routine ultrasound scanning in the entire population at 32 + 0 to 33 + 6 weeks. Models were constructed based on 1393 patients and validated in 1303 patients, including 73 (5.2%) and 82 late FGR (6.3%) cases, respectively. At the second-trimester scan, the a-posteriori second-trimester risk (a-posteriori first-trimester risk (baseline a-priori risk and mean arterial blood pressure) combined with second-trimester abdominal circumference and UtA Doppler) yielded an area under the receiver-operating characteristics curve (AUC) of 0.81 (95% CI, 0.74-0.87) (detection rate (DR), 43.1% for a 10% false-positive rate (FPR)). The combination of a-posteriori second-trimester risk plus third-trimester estimated fetal weight (full model) yielded an AUC of 0.92 (95% CI, 0.88-0.96) (DR, 74% for a 10% FPR). Subjecting 10%, 25% or 50% of the study population to third-trimester ultrasound, based on a-posteriori second-trimester risk, gave AUCs of 0.81 (95% CI, 0.75-0.88), 0.84 (95% CI, 0.78-0.91) and 0.89 (95% CI, 0.84-0.94), respectively. Only the 50% contingent model proved statistically equivalent to performing routine third-trimester ultrasound scans (AUC, 0.92 (95% CI, 0.88-0.96), P = 0.11). A strategy of selecting 50% of the study population to undergo third-trimester ultrasound examination, based on accrued risk in the second trimester, proved equivalent to routine third-trimester ultrasound scanning in predicting late FGR.


Does resident involvement effect surgical times and complication rates during laparoscopic appendectomy for uncomplicated appendicitis? An analysis of 16,849 cases from the ACS-NSQIP.
Controversy exists regarding whether resident involvement during surgery impacts patient outcomes. We compared surgical times and perioperative complications of patients undergoing laparoscopic appendectomy with and without residents. Patients undergoing laparoscopic appendectomy for uncomplicated acute appendicitis during 2005 to 2008 were identified from the American College of Surgeons National Surgical Quality Improvement Program database. During the study period, 16,849 patients underwent laparoscopic appendectomy for uncomplicated appendicitis (residents participated in 68% of procedures). There were no statistical and/or clinically meaningful differences between median age, sex, body mass index, American Society of Anesthesiology score, and morbidity probability between the 2 groups, suggesting that case mix was not a significant confounder. Patients undergoing laparoscopic appendectomy with residents compared with patients undergoing laparoscopic appendectomy without residents had a higher incidence of serious and overall morbidity and longer surgical times. However, surgical times and complications were similar between residents in postgraduate years 1 to 5. Regardless of the postgraduate year level, resident involvement resulted in a clinically appreciable increase in surgical times and a statistically significant increase in certain complications.


The patient coordinator in a liver transplant program.
The specific role of patient coordinator varies among different transplantation centers. Their role is often dependent upon the total number of patients that are being followed at a given center. With continued success of a program and continued patient survival, the functions of the patient coordinator will increase. However, the coordinator's primary mission will remain principally that of patient educator and liaison with the transplant center.


Role of aspartate 27 in the binding of methotrexate to dihydrofolate reductase from Escherichia coli.
Dihydrofolate reductase from wild-type Escherichia coli (WT-ECDHFR) and from a mutant enzyme in which aspartate 27 is replaced by asparagine have been compared with respect to the binding of the inhibitor methotrexate (MTX). Although the Asp27----Asn substitution causes only small changes in the association rate constants (kon) for the formation of binary and ternary (with NADPH) complexes, the dissociation rate constants for these complexes (koff) are increased for the mutant enzyme by factors of about 5- and 100-fold, respectively, at pH 7.65. In binding experiments, the initial MTX binary and ternary complexes of the mutant enzyme were found to undergo relatively rapid isomerization (kobs approximately 17 and 145 s-1, respectively). Although such rapid isomerization of complexes of WT-ECDHFR could not be detected in binding experiments, evidence of a slow isomerization (k = 4 x 10(-3) s-1) of the ternary WT-ECDHFR.MTX.NADPH complex was obtained from progress of inhibition experiments. This slow isomerization increases binding of MTX to WT-ECDHFR only 2.4-fold (much less than previously estimated). From presently available data, we could not determine the contribution of the rapid isomerization of complexes to the binding of MTX to the mutant enzyme. The Asp27----Asn substitution increases the overall dissociation constant (KD) 9-fold for the binary complex and 85-fold for the ternary complex. When it is also taken into account that a proton ultimately derived from the solvent must be added to MTX bound to the WT enzyme, but not to MTX bound to the mutant enzyme, these increases in KD for the mutant enzyme correspond to decreases in binding energy for MTX of 3.9 and 5.2 kcal/mol at pH 7.65 for the binary and ternary complexes, respectively.


Transcriptional regulation of the plastocyanin and cytochrome c553 genes from the cyanobacterium Anabaena species PCC 7937.
The effect of copper on the levels of plastocyanin (PC) and cytochrome c553 (cyt-c)-specific transcripts from Anabaena sp. PCC 7937 was investigated. The addition of copper resulted in a marked increase in PC mRNA levels, and a decrease in cyt c mRNA levels. Thus the functional exchange between PC and cyt c seems to be regulated at the mRNA level. The copper-dependent increase in PC and decrease in cyt c mRNA levels was abolished when chloramphenicol was added to the cells. This suggests that de novo synthesis of at least one trans-acting element is required to regulate PC and cyt c mRNA levels. Both PC and cyt c mRNA stability was found to be unaltered under varying Cu2+ regimes. This leads to the conclusion that expression of both genes is regulated at the level of initiation of transcription.


Tenuigenin treatment improves behavioral Y-maze learning by enhancing synaptic plasticity in mice.
Polygala tenuifolia root has been used to improve memory and cognitive function in Traditional Chinese Medicine for more than 2000 years. Since tenuigenin (TEN) is one of the most utilized P. tenuifolia root extracts, it is surprising there is no evidence for the effects of TEN on learning and memory so far. In the present study, we investigated the effects of TEN on learning and memory with Y-maze test in mice. We found that oral administration of 4mg/kg TEN significantly improved learning and memory in Y-maze task. Treatment with 4mg/kg TEN markedly reduced the acetylcholinesterase (AChE) activity and malondialdehyde (MDA) level, and increased superoxide dismutase (SOD) activity in hippocampus. In the electrophysiological test of hippocampal brain slice, 2μg/ml TEN perfusion substantially enhanced field excitatory postsynaptic potential (fEPSP) amplitude both in basic synaptic transmission and after high frequency stimulation (HFS) in Schaffer to CA1 pathway (Scha-CA1). These results indicate that TEN enhancing learning and memory may result from inhibiting AChE activity, improving antioxidation and enhancing synaptic plasticity in mice. Therefore, TEN shows promise as a potential nootropic product in improving learning and memory.


Competing Robotic Systems: A Preview.
"The new frontier of robotic surgery is well under way. Current research and development is rapidly progressing, allowing for the creation of many new robotic companies. Each company has its own identity and platform for what their vision for the future entails. The competition generated between these companies will shortly be forcing newer, cheaper, more accessible robotic systems worldwide."


Preparation of MnO2 decorated Co3Fe1Ox powder/monolithic catalyst with improved catalytic activity for toluene oxidation.
In this paper, KMnO4 was used to pre-treat Co3Fe-layered double hydroxides (LDH) precursor to prepare MnO2 decorated Co3Fe1Ox catalyst. The toluene oxidation performance of the catalyst was investigated systematically. The optimized 0.1MnCF-LDO catalyst exhibited the best catalytic performance, and the temperatures of 50% and 90% toluene conversion (T50 and T90) were 218 and 243°C, respectively. The apparent activation energy (Ea) was 31.6 kJ/mol. The characterization results showed that the pre-redox reaction by KMnO4 could increase the specific surface area, Co3+ species amount and oxygen defect concentration of the catalyst, which are the main reason of the improved toluene catalytic activity. Besides, this method was also applied to enhance toluene oxidation of iron mesh based monolithic catalyst. The 0.1MnCF-LDO/Iron mesh (IM) catalyst showed a 90% toluene conversion at around 316°C which was much lower than that of without MnO2 addition (359°C). In addition, the water resistant of all the catalysts was studied as well, all the samples showed relatively good water resistance. The toluene conversion still remained to be over >80% even in the presence of 10 vol.% water vapor.


Occurrence of individual trans-isomeric fatty acids in human myocardium, jejunum and aorta in relation to different degrees of atherosclerosis.
With the aid of a highly selective capillary column coated with SP 2340, individual trans-fatty acids were identified in all tissue samples studied, the values being unrelated to the degree of atherosclerosis. The mean values of total trans-acids present in human myocardium, jejunum and aorta amounted to less than 1% of the total fatty acids. The trans-acid content was composed of traces of 9-trans-tetradecenoic acid and nearly equal amounts of 9-trans-hexadecenoate and trans-octadecenoate, the double bond in the latter occurring in the delta6, delta9 and delta11 positions. 9-trans,12-trans-octadecadienoate or the corresponding mixed geometric isomers could not be identified in any sample. Additionally, significant increases of 20:4c(n-6), 22:4c(n-6) and 22:6c(n-3) acids were measured in the myocardium of patients who had died from severe atherosclerosis of the aorta and coronary arteries. The atherosclerosis was not attributable to different dietary habits, as judged from the content of linoleic acid in their adipose tissue.


Detection of surface differences between two closely related cell populations by partitioning isotopically labeled mixed cell populations in two-polymer aqueous phases. I. Human red blood cell subpopulations.
The partition behavior of cells in dextran-poly(ethylene glycol) aqueous phases (i.e., the cells' relative affinity for the top or bottom phase or their adsorption at the interface) is greatly dependent on the polymer concentrations and ionic composition and concentration. Appropriate selection of phase system composition permits detection of differences in either charge-associated or lipid-related surface properties. We have now developed a method that can reveal differences by partitioning that fall within experimental error if one were to compare countercurrent distribution (CCD) curves of two closely related cell populations run separately. One cell population is isotopically labeled in vitro (e.g., with 51Cr-chromate) and is mixed with an excess of the unlabeled cell population with which it is to be compared. The mixture is subjected to CCD and the relative specific radio-activities are determined through the distribution. As control we also examine a mixture of labeled cells and unlabeled cells of the same population. The feasibility of this method was established by use of cell mixtures the relative partition coefficients of which were known. The procedure was then used to test for human erythrocyte subpopulations. 51Cr-chromate-labeled human young or old red blood cells were mixed with unfractionated erythrocytes and subjected to CCD in a phase system reflecting charge-associated properties. It was found that older cells had a high, young cells (probably only reticulocytes) a low partition coefficient. Because of the small differences involved these results were not previously obtained. It was further determined, by repartitioning 51Cr-labeled cells from the left or right ends of a CCD of human red blood cells admixed to unlabeled unfractionated erythrocytes, that a subpopulation with higher partition coefficient exists (probably constituting the old red cells). These experiments serve to illustrate (a) that human red blood cells, contrary to a previous report, can be subfractionated by partitioning and (b) the usefulness of this new method in detecting smaller surface differences between closely related cell populations than was heretofore possible by partitioning alone.


Central line associated and primary bloodstream infections.
Primary and intravascular catheter-associated bloodstream infections (CA-BSIs) represent an important clinical entity in the intensive care unit (ICU) being associated with significant morbidity and mortality. The purpose of this review was to examine the recently published data on epidemiology and management of CA-BSI and other primary BSIs specifically within the context of the ICU. In critically ill patients, the pooled prevalence of primary and CA-BSI from contemporary studies was 19.7-40.7% and 26.4-37.3% of all BSIs, respectively. Failure to achieve source control (i.e., removal of catheter in CA-BSI) is associated with higher mortality. Higher severity scores and durations of ICU stay and catheter insertion are well established risk factors for CA-BSI. The use of prevention bundles when inserting a central venous line is able to reduce CA-BSI incidence from 4 to 1.6 episodes per 1000 central venous catheter days. Differential time-to-positivity of paired blood cultures may assist in the diagnosis of CA-BSI. Primary BSI is frequently observed in ICU cohorts and has a poor effect on outcome. Surveillance for BSI among patients admitted to ICUs is fundamental to inform healthcare service delivery, design preventive approaches, to track resistance, and detect emerging pathogens.


Expression of a potential metastasis suppressor gene (nm23) in thyroid neoplasms.
Identification of multiple clinical and pathologic prognostic factors in differentiated thyroid cancer has permitted some degree of risk stratification. However, these clinical indices fail to distinguish potential intrinsic differences in tumor virulence. The nm23 gene has been identified as a potential metastasis suppressor gene that is homologous to nucleoside diphosphate kinases. Studies in human breast cancer have shown a significant inverse correlation between nm23 levels and nodal involvement/tumor recurrence. Given the possible clinical utility of a marker of metastatic potential in the management of thyroid carcinoma, we examined 34 thyroid neoplasms and a human medullary thyroid cancer (MTC) cell line (TT) for nm23 expression. Normalized nm23 expression was assessed by Northern analysis of tumor RNA. nm23 Expression (tumor expression/TT cell expression, mean +/- SE) was 1.14 +/- 0.15* in MTCs (n = 5), 0.70 +/- 0.10* in follicular cancers (n = 6), 0.51 +/- 0.11 in papillary cancers (n = 19), and 0.31 +/- 0.03 in follicular adenomas (n = 4) (*p < 0.05 when compared to adenomas). Within histologic groups, we found no correlation between nm23 expression and nodal involvement of distant metastases. Our results indicate that thyroid neoplasms of different histologies express varying levels of the nm23 transcript. Although nm23 expression seems diminished in metastatic breast cancer, it appears not to be the case in metastatic thyroid cancer. The nm23 gene may therefore have different roles in the evolution and metastases of different neoplasms.


The role of the preBCR, the interleukin-7 receptor, and homotypic interactions during B-cell development.
Considerable progress has been made in defining intermediate stages in the process leading from stem cells to mature B cells. Cell-bound and secreted molecules direct the progression through these stages and regulate the selection of clones from which the immune repertoire emerges. In fact, a myriad of signals derived from B-cell progenitors themselves and the microenvironment in which they develop direct the differentiation process. These signals are provided by B-cell antigen receptors (BCR) and their surrogates, and by adhesion and cytokine receptors. The co-operation of these receptors to control survival, expansion, and differentiation of early B-cell progenitors is the topic of this review. Specifically, we will summarize recent findings from our laboratory demonstrating that preBCR expression lowers the threshold for interleukin (IL)-7 responsiveness. How signals initiated by these receptors may intersect at this critical point of B-cell selection will be discussed. At the stage following IL-7 responsiveness we have shown that interactions between B-cell progenitors themselves promote their differentiation to immunoglobulin-secreting B cells. We propose that one function of stromal cells, known to be central to B lymphopoiesis, is to promote critical preB-preB homotypic interactions and ensuing signals.


Retrogenes moved out of the z chromosome in the silkworm.
Previous studies on organisms with well-differentiated X and Y chromosomes, such as Drosophila and mammals, consistently detected an excess of genes moving out of the X chromosome and gaining testis-biased expression. Several selective evolutionary mechanisms were shown to be associated with this nonrandom gene traffic, which contributed to the evolution of the X chromosome and autosomes. If selection drives gene traffic, such traffic should also exist in species with Z and W chromosomes, where the females are the heterogametic sex. However, no previous studies on gene traffic in species with female heterogamety have found any nonrandom chromosomal gene movement. Here, we report an excess of retrogenes moving out of the Z chromosome in an organism with the ZW sex determination system, Bombyx mori. In addition, we showed that those "out of Z" retrogenes tended to have ovary-biased expression, which is consistent with the pattern of non-retrogene traffic recently reported in birds and symmetrical to the retrogene movement in mammals and fruit flies out of the X chromosome evolving testis functions. These properties of gene traffic in the ZW system suggest a general role for the heterogamety of sex chromosomes in determining the chromosomal locations and the evolution of sex-biased genes.


Strong buffering capacity of insect cells. Implications for the baculovirus expression system.
Insect cells are widely used for expression of a variety of different proteins by using the baculovirus expression system. The applicability of this system depends on production of proteins which have biological properties similar to their native counterparts. One application has been the expression of viral capsid proteins and their assembly into empty capsid structures to provide new viral immunogens which retain complex antigenic sites. An important parameter for efficient folding and assembly of proteins into viral procapsids may be the intracellular pH, particularly for acid-labile particles such as foot-and-mouth disease virus (FMDV). Benzoic acid was used as an effective indicator of intracellular pH in insect cells and 3-O-methyl glucose to measure cell volumes. We have determined the intracellular volume of theSpodoptera frugiperda IPLB-Sf21 insect cells 0.50±0.08 pL per cell. Using the distribution of [(14)C]-benzoic acid, we show that the intracellular pH remains constant at pH 7.0 when the cells are grown in media with pH values ranging from 6.2 to 6.8 and, moreover, is not affected by baculovirus infection. These results suggest that insect cells are suitable to express and produce acid-labile structures via the baculovirus expression system and that assembly of proteins and viral procapsids could occur.


Sarcoidosis presenting as palmar erythema.
Sarcoidosis, a multisystem disease of unknown aetiology, is characterized by the formation of non-caseating granulomas which may involve any organ of the body. The commonest sites of predilection are the lungs, skin and lymph nodes. We now report a patient who presented with palmar erythema which on biopsy confirmed the presence of non-caseating granulomas and who responded to systemic corticosteroids. We are unaware of any previous report in the literature of sarcoidosis presenting in this way.


Value of contrast-enhanced MR angiography for the follow-up of treated brain arteriovenous malformations: systematic review and meta-analysis.
To estimate the diagnostic value of contrast-enhanced MR angiography (CE-MRA) in identifying residual brain arteriovenous malformations (AVMs) after treatment. We retrieved appropriate references from the electronic databases of PubMed, Web of Science, Embase, and Cochrane Library, and then evaluated the methodology quality of included references using the QUADAS-2 tool. We calculated the pooled sensitivity and specificity by applying a bivariate mixed-effects model and detected the publication bias using Deeks' funnel plot. The values of I2 were used to test heterogeneity and meta-regression analyses were performed to search for the causes of heterogeneity. We included 7 eligible studies containing 223 participants. Compared with a gold standard, the overall sensitivity and specificity of CE-MRA in detecting residual brain AVMs were 0.77 (95% CI 0.65-0.86) and 0.97 (95% CI 0.82-1.00), respectively. Based on the summary ROC curve, the AUC was 0.89 (95% CI 0.86-0.92). Heterogeneity could be observed in our study, especially for the specificity (I2 = 74.23%). Furthermore, there was no evidence of publication bias. Our study provides evidence that CE-MRA has good diagnostic value and specificity for the follow-up of treated brain AVMs. Nevertheless, considering the small sample size, heterogeneity, and many factors that may affect the diagnostic accuracy, future large-sample, prospective studies are necessary to validate the results. • The pooled sensitivity and specificity of contrast-enhanced MR angiography (CE-MRA) in detecting residual arteriovenous malformations (AVMs) were 0.77 (95% CI 0.65-0.86) and 0.97 (95% CI 0.82-1.00). • The four-dimensional CE-MRA showed less sensitivity than the three-dimensional CE-MRA for treated AVMs. • CE-MRA is helpful to identify residual AVMs and reduce excessive DSA during follow-up.


Input stimuli for obtaining frequency responses of automatic gain control hearing aids.
Developing a family of frequency response curves for AGC types of hearing instruments using swept pure tones at varying input levels often produces erroneous results. This problem is caused by exceeding the threshold for activating the AGC circuit at some frequencies but not at other frequencies during the pure-tone sweep, thereby producing a different frequency response from that which would be obtained with a complex input signal such as speech-shaped noise. This measurement artifact may be minimized by ensuring that the threshold for activating the AGC circuit is either always exceeded or never exceeded during the development of a frequency response curve. Three input signals are compared for developing a family of frequency responses for an AGC hearing aid: (1) swept pure tone, (2) swept pure tone with bias tone added, and (3) shaped broad-band noise. The shaped broad-band noise appears to be the input signal of choice.


Ca2+ signaling and the Hippo pathway: Intersections in cellular regulation.
The Hippo signaling pathway is a master regulator of organ size and tissue homeostasis. Hippo integrates a broad range of cellular signals to regulate numerous processes, such as cell proliferation, differentiation, migration and mechanosensation. Ca2+ is a fundamental second messenger that modulates signaling cascades involved in diverse cellular functions, some of which are also regulated by the Hippo pathway. Studies published over the last five years indicate that Ca2+ can influence core Hippo pathway components. Nevertheless, comprehensive understanding of the crosstalk between Ca2+ signaling and the Hippo pathway, and possible mechanisms through which Ca2+ regulates Hippo, remain to be elucidated. In this review, we summarize the multiple intersections between Ca2+ and the Hippo pathway and address the biological consequences.


Noun-verb ambiguity in chronic undifferentiated schizophrenia.
This study investigated noun-verb retrieval patterns of 30 adults with chronic undifferentiated schizophrenia and 67 typical adults, to determine if schizophrenia affected nouns (associated with temporal lobe function) differently from verbs (associated with frontal lobe function). Stimuli were homophonic homographic homonyms, balanced according to frequency of occurrence, where N>V, N<V, or N approximately V. Systematicity effects, in which systematic noun and verb meanings are transparently related (e.g., "drain"), and unsystematic noun and verb meanings appear to be unrelated (e.g., "seal"), were also examined. Adults with schizophrenia overselected nouns, in both phrase and sentence tasks. Typical participants strongly preferred verbs in the phrase task, but nouns in the sentence task. Frequency of occurrence yielded statistically significant effects in control, but not in experimental groups. Effects of systematicity were statistically significant in some, but not all tasks and conditions. Age of typical participants was not significant. Readers will be introduced to (a) evidence of noun-verb organization in the brain; (b) evidence of ambiguous noun-verb preference to differentiate the language of schizophrenia from the language of typical adults; and (c) evidence of ambiguous noun-verb preference to differentiate the language of schizophrenia from fluent aphasia.


Characterization of synthetic carrier ampholytes for isoelectric focusing.
The synthesis of carrier ampholytes suitable for isoelectric focusing is described. The mixture of hexamethylenetetramine (HMTA), triethylenetetramine (TETA), tetraethylenepentamine (TEPA) and pentaethylenehexamine (PEHA) ampholytes closely resembles commercial Ampholine, and covers the pH range 3-9.5. We have been able to detect focused ampholytes in a gel slab, taking advantage of their different refractive indices, and to assess their relative amounts along the pH gradient. PEHA ampholytes contain up to 20% of chromophoric structures, with two UV peaks at 368 and 315 nm, in a pH-dependent equilibrium, associated with a very weak nitrogen function having a pK of 1.1. This could be the pK6 of the last amino group in PEHA. However, NMR spectra failed to reveal any nitrogen heterocyclic structure formed during the synthesis. This mixture of ampholytes exhibits good conductivity, produces smooth pH gradients and allows sharp protein separations in the pH range 3-9.5. Their synthesis is very easy and their cost is extremely low. Their availability sould make feasible large-scale preparative isoelectric focusing, and attract more interest to continuous-flow techniques, where large amounts of ampholytes are required.


Sex hormones and the incidence of severe retinopathy in male subjects with type I diabetes.
Diabetic retinopathy rarely occurs before puberty, suggesting that changes in sex hormones may influence the development of this condition. The authors measured total testosterone, free testosterone, sex hormone-binding globulin, estradiol, and dehydroepiandrosterone-sulfate levels in 44 men with type I diabetes participating in the 1984 to 1986 re-examination phase of the Wisconsin Epidemiologic Study of Diabetic Retinopathy, a population-based study of diabetic complications. The mean age was 32.7 years, and the mean duration of diabetes was 15.4 years. Subjects who progressed to proliferative or preproliferative retinopathy 6 years later (cases, n = 22) were compared with subjects who had little or no progression (controls, n = 22). Both groups were matched on initial level of retinopathy. Seven stereoscopic retinal photographs of each eye were obtained at both examinations, and the photographs were read by the University of Wisconsin Reading Center. Sex hormone-binding globulin concentrations (nmol/l) were significantly lower (reflecting increased androgenicity) in cases than in controls (22.4 +/- 11.4 versus 32.5 +/- 19.8; P = 0.04). No other statistically significant differences in hormone levels were observed. Neither serum testosterone nor other sex hormones were related to the incidence of severe retinopathy. The relationship to low-serum sex hormone-binding globulin suggests that increased androgenicity may be associated with the progression of retinopathy in male subjects with type I diabetes.


The mechanism of mitral regurgitation in dilated left ventricle.
To assess the mechanism of mitral regurgitation in ventricular dilatation, 24 patients with dilated cardiomyopathy (13 with and 11 without mitral regurgitation) and 10 normal individuals were studied by two-dimensional echocardiography. Left ventricular dimensions and mitral ring diameters in systole and diastole were measured in the long-axis section, and systolic interpapillary muscle distance in the short-axis section. The results showed: Mitral ring diameter is increased in most patients with dilated cardiomyopathy. Neither increased ring diameter, reduced ring contraction, nor decreased interpapillary muscle distance determine the presence of mitral regurgitation. The only difference between those patients with and without mitral regurgitation was the degree of left ventricular dilatation (p less than 0.05).


Increased endogenous reactive oxygen species normalizes proliferation defects of Bmi1 heterozygous knockout neural stem cells.
The Bmi1gene, one of transcriptional suppressor genes in multi-comb family, maintains proliferation of neural stem cells (NSCs) and redox homeostasis. However, heterozygous deletion of the Bmi1 gene (Bmi1+/-) does not reduce the proliferative ability of NSCs. The aim of the present study was to reveal the underlying mechanism of this phenotype. NSCs derived from the cortex of newborn Bmi1+/- and wild-type (WT) mice were treated with different concentrations of hydrogen peroxide (H2O2) and antioxidant N-acetyl-L-cysteine (NAC) for 24 h followed by analyses of NSC proliferation and oxidative stress-related indexes. The levels of reactive oxygen species (ROS) of Bmi1+/--NSCs were slightly higher than that of WT-NSCs at baseline. H2O2 increased ROS and NAC reduced ROS in a concentration-dependent pattern, but the change was significantly greater in Bmi1+/--NSCs than WT-NSCs. The proliferation and self-renewal ability of Bmi1+/--NSCs and WT-NSCs were comparable in a basic state. After 1 μM H2O2 treatment, Brdu incorporation ratio, cell viability, total antioxidant capacity (T-AOC) and total superoxide dismutase activity were increased slightly in WT-NSCs, but decreased in Bmi1+/--NSCs. H2O2 at 10 μM decreased proliferation and self-renewal ability of both genotype NSCs, with greater effect in Bmi1+/-. After treatment with 1 mM NAC, the number and diameter of neurospheres, Brdu incorporation rate, cell viability, T-AOC and total superoxide dismutase activity of Bmi1+/--NSCs were lower than those of WT-NSCs. These results suggest that Bmi1+/--NSCs exhibit normal proliferation and self-renewal due to a slight increase in ROS, but are more vulnerable to changes in redox status.


Diabetes mellitus is not associated with major morbidity following open abdominal aortic aneurysm repair.
It has been suggested that there is an increased morbidity and mortality risk for diabetics undergoing elective aortic surgery. This, however, is not universally accepted. In this study, we utilize a national database to determine if diabetes is associated with adverse outcomes following open, elective, infrarenal abdominal aortic aneurysm (AAA) repair. The American College of Surgeons' National Surgical Quality Improvement Program database was queried to identify all patients who underwent an open, elective, nonruptured AAA repair from January 1, 2005 to December 31, 2007. Patient demographics, comorbidities, and outcomes were compared by diabetes status. Multivariate analysis was performed adjusting for demographics and comorbidities. There were 2110 American College of Surgeons' National Surgical Quality Improvement Program patients who underwent an open, elective, nonruptured AAA repair during this time period. Of these patients, 245 (11.6%) had diabetes mellitus. The overall mortality rate was 3.7% (5.3% for diabetics and 3.5% for nondiabetics, P = 0.171). On bivariate analysis, diabetics were more likely to present preoperatively with cardiovascular and renal comorbidities. Postoperatively, there was no significant difference in mortality or in cardiac, pulmonary, or renal complications. Diabetics were more likely to develop superficial surgical site infections (SSIs) (4.5% versus 1.6%, P = 0.002). On multivariate regression, there was no difference in mortality or major complications between diabetics and nondiabetics (OR 1.4, 95% CI 0.68-2.71). Diabetics, however, were almost three times more likely to develop superficial SSIs (OR 2.8, 95% CI 1.29-6.00). Diabetes mellitus is not associated with significantly worse major outcomes following open, elective, infrarenal AAA repair. Diabetics, however, are more likely to develop superficial SSIs.


Differential inhibition of the DNA translocation and DNA unwinding activities of DNA helicases by the Escherichia coli Tus protein.
Binding of the Escherichia coli Tus protein to its cognate nonpalindromic binding site on duplex DNA (a Ter sequence) is sufficient to arrest the progression of replication forks in a Ter orientation-dependent manner in vivo and in vitro. In order to probe the molecular mechanism of this inhibition, we have used a strand displacement assay to investigate the effect of Tus on the DNA helicase activities of DnaB, PriA, UvrD (helicase II), and the phi X-type primosome. When the substrate was a short oligomer hybridized to a circular single-stranded DNA, strand displacement by DnaB, PriA, and the primosome (in both directions), but not UvrD, was blocked by Tus in a polar fashion. However, no inhibition of either DnaB or UvrD was observed when the substrate carried an elongated duplex region. With this elongated substrate, PriA helicase activity was only inhibited partially (by 50%). On the other hand, both the 5'----3' and 3'----5' helicase activities of the primosome were inhibited almost completely by Tus with the elongated substrate. These results suggest that while Tus can inhibit the translocation of some proteins along single-stranded DNA in a polar fashion, this generalized effect is insufficient for the inhibition of bona fide DNA helicase activity.


Dramatic response to nivolumab in xeroderma pigmentosum skin tumor.
We report the case of a 6-year-old female with xeroderma pigmentosum (XP) who developed a nonoperable scalp tumor, treated with anti-programmed cell death protein 1 (anti-PD-1) therapy (nivolumab). She presented with a sarcomatoid carcinoma of the scalp with bone lysis as well as vascular and meningeal contact. Nivolumab was initiated because it has emerged as a promising immunotherapy. We observed a dramatic tumor response with excellent tolerance. However, while on nivolumab therapy she developed two large skin melanomas and several squamous cell carcinomas, which have been resected. These results demonstrate that cancer immunotherapy in patients with XP can be impressive but complex and warrants further investigation.


Extruded urea levels in lamb supplementation in rainy tropical savanna conditions: the triad host-gastrointestinal nematodes-environment.
The objective of this study was to evaluate the influence of increasing levels of extruded urea (EU, Amireia®) in the diet of lambs naturally infected by gastrointestinal nematodes on the interactions in the host-pasture-soil components in edaphoclimatic conditions of the tropical rainy savanna. A total of 60 Texel lambs with a mean initial weight of 20.7 ± 0.87 and mean age of 2.5 ± 0.70 months were distributed in a completely randomized design, in five treatments consisting of different levels of EU supplementation viz., 0, 6, 12, 18, and 24 g 100 kg-1 live weight (LW). The performance of lambs, parasitological variables, gastrointestinal nematodes (NGIs), and larvae recovery in pasture and soil were evaluated. The highest animal performance was observed in animals that received 0 to 18 g kg-1 LW (146.0 g day-1) and the lowest in animals supplemented with 24 g kg-1 LW (81.0 g day-1) of EU. The body condition score (BCS) was similar in the animals (P > 0.05). Parasitic infection did not differ as a function of EU level (P > 0.05). Eggs of Haemonchus spp., Trichostrongylus spp., Cooperia spp., and Oesophagostomum spp. were found. The largest amount of larvae in the L1/L2 and L3 stages was recovered in the pastures occupied by the animals that received supplementation 0 g kg-1 LW of EU (750 larvae), the smallest in those that the animals received 6 g 100 kg-1 LW of EU (54 larvae). The presence of larvae in the L1/L2 stages changed significantly (P < 0.05) in the soil; in the other stages, it did not differ in the soil. Increasing levels of extruded urea do not influence the eggs per gram of feces (EPG) count. The 0 to 18 g 100 kg-1 LW level maintains animal performance, BCS and FAMACHA©. There is less dispersal of NGI larvae in pasture and soil when EU levels increase in the edaphoclimatic conditions of the rainy tropical savannah, which suggests that this supplement can be implemented in the diet of beef lambs, in addition to to be a lower cost nitrogen source.