A Smartphone-Only Pulse Transit Time Monitor Based on Cardio-Mechanical and Photoplethysmography Modalities.
This paper reports a system for monitoring pulse transit time (PTT). Using an Android smartphone and a customized sensing circuit, the system collects seismo-cardiogram (SCG), gyro-cardiogram (GCG), and photoplethysmogram (PPG) recordings. There is no need for any other external stand-alone systems. The SCG and GCG signals are recorded with the inertial sensors of the smartphone, while the PPG signal is recorded using a sensing circuit connected to the audio jack of the phone. The sensing circuit is battery-less, powered by the audio output of the smartphone using an energy harvester that converts audio tones into DC power. PPG waveforms are sampled via the microphone channel. A signal processing framework is developed and the system is experimentally verified on twenty healthy subjects at rest. The PTT is measured as the time difference between the aortic valve (AO) opening points in SCG or GCG and the fiducial points in PPG. The root-mean-square errors between the results from a stand-alone sensor system and the proposed system report 3.9 ms from SCG-based results and 3.4 ms from GCG-based results. The detection rates report more than 97.92% from both SCG and GCG results. This performance is comparable with stand-alone sensor nodes at a much lower cost.


Iatrogenic metatarsal coalition: a postoperative complication of adjacent V-osteotomies.
The authors present a case report of iatrogenic metatarsal coalition, a postoperative complication of adjacent V-osteotomies. The paper also includes a discussion of surgical considerations of multiple adjacent osteotomies contributing to such a sequela, including adequate irrigation, instrumentation, anatomy, and the use of corticosteroids.


Effect of isocaloric low-fat diet on human LAPC-4 prostate cancer xenografts in severe combined immunodeficient mice and the insulin-like growth factor axis.
Over-consumption of dietary fat has been suggested to promote the development and progression of prostate cancer in men. The present study was conducted to answer the following questions: (a) Can dietary fat reduction decrease tumor growth rates of Los Angeles prostate cancer (LAPC)-4 xenografts in severe combined immunodeficient (SCID) mice independent of total caloric intake? and (b) Is the insulin-like growth factor (IGF) axis involved in the effects of dietary fat on LAPC-4 tumor growth in SCID mice? Twenty-eight male CB17 beige SCID mice (8 weeks old) were individually caged, randomized, and fed an isocaloric high-fat (HF, 42% kcal) or low-fat (LF, 12% kcal) diet. Each mouse was s.c. injected with 1 x 10(5) LAPC-4 cells, and tumor volumes were measured weekly. At week 16, all animals were sacrificed, and serum and tumors were obtained for analysis. Although caloric intakes and mouse weights were equal between groups, the LF mice had significantly slower tumor growth rates and lower serum prostate-specific antigen levels compared with the HF mice. LF mice had significantly lower levels of serum insulin, tumor IGF-1 mRNA expression, and tumor IGFBP-2 immunostaining and higher levels of serum IGFBP-1 (by Western ligand blot) relative to the HF mice. There were no differences in the serum levels of IGFBP-3 and IGFBP-4 between the groups. LAPC-4 cells cultured in vitro with media containing serum from LF mice demonstrated slower growth than LAPC-4 cells cultured in media containing HF mice serum. These results demonstrate that intake of an LF diet was associated with slower LAPC-4 prostate tumor growth relative to mice fed an HF diet, independent of total caloric intake, and this effect may be mediated through modulation of the insulin/IGF axis.


Optical design in a flow system for imaging cells.
The imaging flow cytometer is an instrument that acquires the images of cells in a flow system. These images are analyzed for real-time cell classification and sorting. The optical units in the system perform the functions of laser beam focusing, cell detection, and cell imaging. The glass nozzle in which the cell stream flows introduces air-glass optical interfaces, resulting in optical aberrations that impair performance. This report describes the analysis of the optical aberrations in nozzles fabricated from a cylindrical glass capillary tube. Flat surfaces could be machined on the originally cylindrical surface to reduce the severity of these aberrations. The analysis shows that a nozzle with three flat surfaces is a feasible low-cost solution.


Molecular characterization of rotaviruses with distinct group antigens.
Comparative serological and nucleic acid studies were carried out on rotavirus isolates, with and without the original group antigen. Indirect immunofluorescence allowed the atypical isolates to be divided into two groups each with its own distinct group antigen hence giving a total of at least three distinct rotavirus groups. Genome profile analysis of the atypical isolates again divided them into two groups which corresponded with those obtained by immunofluorescence and within which the overall pattern of genome segments was similar. A more rigorous examination of the degree of difference between the three virus groups was carried out using single-dimension terminal fingerprint analysis. This indicated that the viruses in the three groups did not carry any genome segments in common with each other. Therefore, experimental criteria have been established which allow the division of rotaviruses into three groups. Analysis of further atypical isolates, as they become available, will establish whether the division of rotaviruses into a number of separate groups, of the type seen in influenza virus, is justified.


Urinary Tract Infection in Young Infants: Practice Patterns in Evaluation and Treatment.
No clear guidelines exist for the management of infants ≤60 days old with urinary tract infection (UTI), although this condition represents a significant percentage of serious bacterial infection in this age group. We examined patterns of UTI management in infants ≤60 days at a tertiary care children's hospital and hypothesized that younger infants would be hospitalized longer. We reviewed electronic health records of infants age ≤60 days with diagnostic codes of UTI or fever hospitalized from January 2013 to January 2017 with urine culture obtained and UTI diagnosis documented. Outcomes were duration of parenteral antibiotic therapy, length of stay (LOS), and hospital readmission. One hundred ninety-three infants met criteria. Median age at admission was 37 days (interquartile range [IQR]: 22-48). Median duration of parenteral antibiotics was 59 hours (IQR 43-114) and median LOS was 71 hours (IQR 57 127). Infants age ≤28 days, with fever duration ≥24 hours, irritability or lethargy on initial examination, and bacteremia received longer parenteral therapy and had longer LOS. In multivariate analysis, age, irritability or lethargy, and presence of bacteremia remained independently related to parenteral therapy duration and LOS. In young infants with UTI, patients aged ≤28 days had longer duration of IV antibiotic therapy and LOS, independent of other clinical characteristics of their illness. The duration of parenteral therapy and LOS was relatively short, although significant variability still existed.


Vitamin D deficiency: a paediatric orthopaedic perspective.
At the turn of the last century, rickets (vitamin D deficiency) was one of the most common musculoskeletal diseases of the paediatric population presenting to physicians. Today, the most common referral pathway for these patients ends in a paediatric orthopaedic outpatient clinic. Vitamin D deficiency is a clinical entity that can affect all children and should be looked for in all children with musculoskeletal symptoms. The child at risk of rickets is now white, breastfed, protected from the sun and obese. Vitamin D deficiency can present as atypical muscular pain, pathological fractures or slipped upper femoral epiphysis. Obesity is linked with lower vitamin D levels; however, in the paediatric population, this does not necessarily equal clinical disorder. Vitamin D supplements can be used to reduce the risk of pathological fractures in the cerebral palsy child. It should also form part of the differential diagnosis in the work-up of nonaccidental injuries. Children with a low vitamin D present with a higher incidence of fractures from normal activities. Vitamin D levels need to be assessed before any form of orthopaedic surgery, as it can affect growth, both in the diaphysis of the bone and in the growth plate. Vitamin D levels are a key element in the successful practice of paediatric orthopaedics. It is not just the possible cause of disorder presenting to the clinician but also extremely important in ensuring the successful postoperative recovery of the patient.


Vapor pressure of nine perfluoroalkyl substances (PFASs) determined using the Knudsen Effusion Method.
Sublimation vapor pressures of nine pure perfluoroalkyl substances, including Ammonium perfluoro(2-methyl-3-oxahexanoate) (GenX), 1H,1H,2H,2H-Perfluoro-1-decanol (8:2 FTOH), 1H,1H,2H,2H-Perfluoro-1-dodecanol (10:2 FTOH) and C6 to C11 perfluorocarboxylic acids (PFCAs), were measured using the Knudsen technique at near ambient temperatures. Melting temperatures and fusion enthalpies of these compounds were also measured using differential scanning calorimetry. The vapor pressure of GenX ammonium salt is comparable to that of the much higher molecular weight perfluoroundecanoic acid. GenX ammonium salt also did not show actual melting behavior but instead decomposed at around 470 K. The measured near ambient temperature sublimation vapor pressures of the PFCAs and FTOHs were compared with some earlier reported liquid phase vapor pressures obtained at higher temperatures, and reasonable agreement exists between the data obtained in the different studies. The sublimation enthalpies of the PFCAs indicate that the contribution to the sublimation enthalpy of the CF2 group in the alkyl chain is comparable to that of the CH2 group in the corresponding non-fluorinated analogues, even though the PFCAs show consistently higher vapor pressures than do the corresponding carbon number alkanoic acids.


[A Case of Surgical Resection for Gallbladder Cancer with Para-Aortic Lymph Node Metastasis Following Neoadjuvant Chemotherapy with Gemcitabine, Cisplatin, and TS-1].
A 60-year-old woman who visited a doctor during postoperative follow-up for breast cancer was found to have elevated CEA levels. Investigation with FDG-PET CT following enhanced CT suggested gallbladder cancer(GBC)accompanied with para-aortic lymph node(PAL)metastasis. Although we could not obtain any histological evidence, we recommended she be treated as a patient with advanced GBC, and she received 8 courses of chemotherapy consisting of gemcitabine, cisplatin, and TS-1, following the protocol of a clinical trial. After the chemotherapy, imaging exhibited down-staging of the GBC, indicating tumor shrinkage and disappearance of the accumulation of FDG at the tumor sites. We first performed cholecystectomy to obtain histological evidence, and subsequently performed pancreaticoduodenectomy and partial hepatectomy at the gallbladder bed. The pathological diagnosis was pT2N1M0, Stage III B, Evans Grade II b; curative grade A surgery was recommended because the PAL did not contain a tumor any more. The prognosis of advanced GBC with PAL metastasis is extremely poor, but conversion therapy with combined modality therapy including neoadjuvant chemotherapy is a useful strategy to achieve a curative resection.


[Arrhythmia in children with dilated cardiomyopathy (data of 24-hour ECG monitoring)].
The authors demonstrate potentialities of long-term ECG monitoring in the diagnosis of heart rhythm and conduction disturbances in children with dilated cardiomyopathy. Provide the results of comparative studies of routine and 24-hour ECG monitoring in children with dilated cardiomyopathy under every-day life conditions. Show that during 24-hour ECG monitoring, all the children with the above pathology manifest heart rhythm and conduction disturbances of varying intensity and prognostic significance.


A mechanistic model of the enzymatic hydrolysis of cellulose.
A detailed mechanistic model of enzymatic cellulose hydrolysis has been developed. The behavior of individual cellulase enzymes and parameters describing the cellulose surface properties are included. Results obtained for individual enzymes (T. reesei endoglucanase 2 and cellobiohydrolase I) and systems with both enzymes present are compared with experimental literature data. The model was sensitive to cellulase-accessible surface area; the EG2-CBHI synergy observed experimentally was only predicted at a sufficiently high cellulose surface area. Enzyme crowding, which is more apparent at low surface areas, resulted in differences between predicted and experimental rates of hydrolysis. Model predictions also indicated that the observed decrease in hydrolysis rates following the initial rate of rapid hydrolysis is not solely caused by product inhibition and/or thermal deactivation. Surface heterogeneities, which are not accounted for in this work, may play a role in decreasing the hydrolysis rate. The importance of separating the enzyme adsorption and complexation steps is illustrated by the model's sensitivity to the rate of formation of enzyme-substrate complexes on the cellulose surface.


Shape bistability of a membrane neck: a toggle switch to control vesicle content release.
Shape dynamics and permeability of a membrane neck connecting a vesicle and plasma membrane are considered. The neck is modeled by a lipid membrane tubule extended between two parallel axisymmetric rings. Within a range of lengths, defined by system geometry and mechanical properties of the membrane, the tubule has two stable shapes: catenoidal microtubule and cylindrical nanotubule. The permeabilities of these two shapes, measured as ionic conductivity of the tubule interior, differ by up to four orders of magnitude. Near the critical length the transitions between the shapes occur within less than a millisecond. Theoretical estimates show that the shape switching is controlled by a single parameter, the tubule length. Thus the tubule connection can operate as a conductivity microswitch, toggling the release of vesicle content in such cellular processes as "kiss-and-run" exocytosis. In support of this notion, bistable behavior of membrane connections between vesicles and the cell plasma membrane in macrophages is demonstrated.


Overexpression of Polo-like kinase 1 is a common and early event in pancreatic cancer.
There is abundant evidence from in vivo and in vitro studies that Polo-like kinase 1 (PLK1) plays a crucial role in the regulation of proliferative activity of normal and malignant cells. Therefore, PLK1 has been proposed as a new target for antineoplastic treatment strategies. We conducted an immunohistochemical expression study for PLK1 on 86 cases of pancreatic adenocarcinoma as well as on 5 cases of chronic pancreatitis. Additionally, we investigated the correlation of PLK1 expression levels with clinicopathological data and patient survival. PLK1 was found overexpressed in pancreatic neoplasia as early as in pancreatic intraepithelial neoplasia III lesions, whereas benign acinar pancreatic parenchyma and ductal epithelia showed only focal PLK1 positivity. Invasive pancreatic adenocarcinomas were PLK1 positive in 47.7% of cases. No correlation of PLK1 positivity and the extent of tumour spread was evident, nor did PLK1 expression correlate with tumour grade or patient prognosis. Prognostic factors in our study cohort were nodal status and tumour grade. The fact that half of the invasive pancreatic carcinomas strongly overexpressed PLK1 indicates that inhibition of this mitotic key regulator might represent a rewarding approach in the treatment of early and late pancreatic carcinoma.


Invasive Pulmonary Aspergillosis: Risks for Acquisition and Death in a Community Hospital.
Recent cases of hospital-acquired (HA) aspergillosis on our Trauma Service raised the question of whether this represented an outbreak or just increased case identification. After Institutional Review Board approval, we performed a retrospective analysis of all 117 patients with positive pulmonary Aspergillus cultures at Grand Strand Medical Center from 2010 through 2016. The diagnosis of community-acquired (CA) invasive pulmonary aspergillosis (IPA) was determined when patients were admitted with a pneumonia and the diagnosis was made within the first week of hospitalization. Of patients with fungus cultures (3929), 3% (117) were positive for Aspergillus. More than 70% (84) of patients were colonized. The remaining 33 patients were treated for IPA. Twenty-seven patients had chronic respiratory problems and presented with a new lower respiratory illness; 23 had CA IPA diagnosed within the first week of admission with 17% mortality rate; four patients had a delayed diagnosis (probable CA) with a 75% mortality rate. The six remaining patients all underwent a surgical procedure and were suspected to have HA aspergillosis. There was a significantly higher rate of HA in the surgical subset in comparison with all nonsurgical patients (p < 0.03). Patients treated for IPA were more likely to be receiving high dose prednisone (>20 mg/day, p < 0.004) and their mortality rate was significantly higher than colonized patients (27.3% vs. 9.5%, p < 0.026). Patients with HA IPA were divided evenly over the years of the study period and not thought to represent an outbreak. Aspergillus infection is an endemic infection in this region of the southern Atlantic states and may occur in patients with major trauma as well as patients with chronic pulmonary diseases. Our data support the concept that there were no breaches in air quality to cause the IPA. Aggressive fungal therapy should be considered in all at-risk patients.


Stacking-ac4C: an ensemble model using mixed features for identifying n4-acetylcytidine in mRNA.
N4-acetylcytidine (ac4C) is a modification of cytidine at the nitrogen-4 position, playing a significant role in the translation process of mRNA. However, the precise mechanism and details of how ac4C modifies translated mRNA remain unclear. Since identifying ac4C sites using conventional experimental methods is both labor-intensive and time-consuming, there is an urgent need for a method that can promptly recognize ac4C sites. In this paper, we propose a comprehensive ensemble learning model, the Stacking-based heterogeneous integrated ac4C model, engineered explicitly to identify ac4C sites. This innovative model integrates three distinct feature extraction methodologies: Kmer, electron-ion interaction pseudo-potential values (PseEIIP), and pseudo-K-tuple nucleotide composition (PseKNC). The model also incorporates the robust Cluster Centroids algorithm to enhance its performance in dealing with imbalanced data and alleviate underfitting issues. Our independent testing experiments indicate that our proposed model improves the Mcc by 15.61% and the ROC by 5.97% compared to existing models. To test our model's adaptability, we also utilized a balanced dataset assembled by the authors of iRNA-ac4C. Our model showed an increase in Sn of 4.1%, an increase in Acc of nearly 1%, and ROC improvement of 0.35% on this balanced dataset. The code for our model is freely accessible at https://github.com/louliliang/ST-ac4C.git, allowing users to quickly build their model without dealing with complicated mathematical equations.


Flash-lamp-pumped Ho:Tm:Cr:YAG and Ho:Tm:Er:YLF lasers: experimental results of a single, long pulse length comparison.
Flash-lamp-pumped, room-temperature Ho:Tm:Cr:YAG and Ho:Tm:Er:YLF are compared for single but long pulse operation, with pulse lengths of approximately 1.0 mus. Under similar operating conditions in normal-mode operation, a slope efficiency of 0.0331 was observed for Ho:Tm:Er:YLF compared with 0.0047 for Ho:Tm:Cr:YAG. For Q-switched operation, Ho:Tm:Er:YLF yielded a slope efficiency of 0.0075. In comparison, a slope efficiency of 0.0012 was obtained for Ho:Tm:Cr:YAG. Two methods of producing long pulse lengths are compared: pulse selection of normal-mode relaxation oscillations and Q-switching in a long resonator. Theoretical models developed in a companion paper for normal-mode relaxation oscillations and Q-switching in quasi-four-level solid-state lasers are in agreement with the experimental results.


Antimicrobial growth promoters used in animal feed: effects of less well known antibiotics on gram-positive bacteria.
There are not many data available on antibiotics used solely in animals and almost exclusively for growth promotion. These products include bambermycin, avilamycin, efrotomycin, and the ionophore antibiotics (monensin, salinomycin, narasin, and lasalocid). Information is also scarce for bacitracin used only marginally in human and veterinary medicine and for streptogramin antibiotics. The mechanisms of action of and resistance mechanisms against these antibiotics are described. Special emphasis is given to the prevalence of resistance among gram-positive bacteria isolated from animals and humans. Since no susceptibility breakpoints are available for most of the antibiotics discussed, an alternative approach to the interpretation of MICs is presented. Also, some pharmacokinetic data and information on the influence of these products on the intestinal flora are presented.


Beta-Adrenoceptor-medicated down-regulation of M2 muscarinic receptors: role of cyclic adenosine 5'-monophosphate-dependent protein kinase and protein kinase C.
Stimulation of beta2-adrenoceptors with the selective beta2 agonist procaterol caused a biphasic decrease in cell surface M2 muscarinic receptor number in human embryonic lung 299 cells when measured with the hydrophilic antagonist [3H]N-methylscopolamine. In contrast, total muscarinic receptor number, measured with the lipophilic antagonist [3H]quinuclidinylbenzilate, decreased after only 24-hr treatments with procaterol. The loss in receptor number at 24 hr was mimicked with the use of forskolin and the cAMP analogue 8-bromo-cAMP, indicating a cAMP-mediated mechanism. Northern blot analysis showed a small and transient increase in m2-receptor mRNA levels up to 2 hr but no long term (24 hr) effect. Chronic (24 hr) treatment with 8-bromo-cAMP also had no effect on m2 muscarinic receptor mRNA, whereas forskolin caused a 50% reduction in the steady state levels of m2 mRNA that could be only partially blocked by the cAMP-dependent protein kinase inhibitor H-8 and the protein kinase C inhibitor GF 109203X. Procaterol-induced down-regulation of M2 receptors was fully blocked by N-[2-(methylamino)ethyl]-5'-isoquinoline-sulfonamide and 2-[1-(3-dimethylaminopropyl)-inol-3-yl]-3-(indol-3-yl)maleimide, implicating both of these kinases in the M2 muscarinic receptor down-regulation. Conversely, the forskolin- and 8-bromo-cAMP-induced down-regulation was only partially inhibited and unaffected by these inhibitors, respectively. In control cells and those treated with procaterol for < / = 2 hr, cAMP generation was significantly inhibited by carbachol. The inhibitory effect of carbachol was, however, lost after 24-hr exposure to procaterol. This desensitization was partially reversed by preincubations with H-8 and GF 109203X. Collectively, these results suggest that transregulation of M2 muscarinic receptors by beta2-adrenoceptor stimulation can be demonstrated at the protein level in human embryonic lung 299 cells. Furthermore, a role is suggested for cAMP-dependent kinase and PKC in M2 muscarinic receptor down-regulation and their functional desensitization.


Electrophysiologic evaluation of the facial nerve in Bell's palsy. A review.
Facial nerve paralysis is the most common mononeuropathy and idiopathic facial paralysis (Bell's palsy) the most common seventh nerve disease electromyographers may be asked to evaluate. The electrophysiologic method of choice to assess the facial nerve is side-to-side evoked amplitude comparison with the affected side expressed as a percentage of the nonaffected side. This examination should be performed on days 3, 5, 7, 9, 11 and 13 after onset of paralysis. If the percentage of surviving axons falls below 10% within the first 14 days, an incomplete recovery is suggested. Electromyography may assist in prognosticating a functional return, determining neural conduction across the site of injury and following reinervation in the recovery period. The persistence or early return of an absent R1 component of the blink reflex may qualitatively suggest a satisfactory functional outcome in facial paralysis. Supramaximally exciting the facial nerve at the stylomastoid foramen and comparing the clinical response on the affected and nonaffected side, maximum stimulation test, can also predict eventual seventh nerve return. Observing a minimal twitch, utilizing the nerve excitability test or measuring the facial nerve latency have yielded poor correlations with functional return and are of limited usefulness in the prognostication of acute facial palsies. Trigeminal somatosensory evoked potentials can be employed to evaluate the status of the trigeminal nerve as approximately 50% of patients with Bell's palsy also have lesions involving the fifth nerve. Side-to-side amplitude comparison and electromyography are the two most valuable electrophysiologic methods of assessing facial nerve functioning.


Soft corticosteroids for local immunosuppression: exploring the possibility for the use of loteprednol etabonate for islet transplantation.
Transplantation of pancreatic islets into subcutaneous, neovascularized devices is one of the possibilities explored as part of our search for a cure of diabetes. We have recently reported that syngeneic transplantation in a subcutaneous prevascularized device can restore euglycemia and sustain long-term function in rats and that explanted grafts showed preserved islets and intense vascular networks. Because all of the transplanted tissue is localized within the device, if such a bioartificial pancreas approach is used, localized immunosuppression might provide sufficient protection against rejection to achieve long-term function, while also avoiding the serious systemic side effects and the susceptibility for opportunistic infections that are commonly associated with systemic immunosuppressive therapies as only much smaller and localized doses are needed. Soft steroids are obvious candidates because soft drugs are specifically designed to produce targeted local activity, but no systemic side effects due to prompt metabolic (preferably extrahepatic, e.g., hydrolytic) inactivation. However, local concentrations that are effective for immunosuppression, but non-toxic to insulin-producing beta-cells have to be found, and nontrivial difficulties related to long-term local deliverability have to be addressed. Here, we report preliminary results obtained using in vitro studies with human islets used to establish a tentative therapeutic concentration range together with fully scaled three-dimensional finite element method (FEM)-based Comsol multiphysics computational models that were used to explore various possibilities to achieve and maintain these concentration levels within the device.


Evaluation of C-Reactive Protein and Associated Factors Among Patients Suffering from Rheumatoid Arthritis at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia.
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder, which is associated with increased pro-inflammatory mediators to induce an elevation in acute-phase response, migration of immune cells and swelling of synovial joints. Evaluation of the level of C-reactive protein and associated risk factors in RA patients was the main aim of this study. Identifying the association between disease activity of RA (hsCRP) and socio-demographic characteristics was another aim of the study. Institution-based cross-sectional study was conducted at the Rheumatology Clinic of Tikur Anbessa Specialized Hospital. In this study, the level of hsCRP was measured in both case and control groups. Simple descriptive statistics, multivariate analysis, independent sample t-test were utilized for statistical analysis. The strength of association between different risk factors and hsCRP was measured using odds ratio and 95% confidence interval. P-value < 0.05 was considered as statistically significant. The result of this study showed that the hsCRP level was significantly higher among RA patients as compared to the control groups (P-value = 0.004). There was an association between smoking and high disease activity status (AOR= 20.03, p= 0.40). Low economic status had a statistically significant association with high hsCRP level (AOR = 12.79, p=0.00). In this study, 42 RA patients had >3mg/l hsCRP level with different occupational exposures. On the other hand, 31 RA patients had <3mg/l hsCRP level among different exposures. Although there was no statistically significant association, the association between associated risk factors (oil consumption, physical exercise, educational status) and disease activity was computed in this study. The inflammatory marker, hsCRP was significantly higher among patients as compared to controls. The higher hsCRP showed a high grade of systemic inflammation in RA patients. C-reactive protein was elevated in rheumatoid factor positive patients and patients with high BMI value. Additionally, the result of our study showed that different socio-economic factors had an association with disease activity of RA.


Chondrolysis complicating slipped capital femoral epiphysis.
In a detailed study of 249 patients, 329 cases who had slipped capital femoral epiphysis treated at the Campbell Clinic during the period from 1935 to 1973, chondrolysis was found in 79 hips in 71 patients (28.9%). The incidence of chondrolysis is correlated with the number of factors, including sex, race, chronicity and severity of displacement, and method of treatment. On the basis of biopsy observations upon 23 patients who had chondrolysis, the natural history of the disease includes self-perpetuating synovitis, and progresses with abnormal mechanical stress on the articular cartilage and the development of osteoarthritis.


[Radioimmunologic assay of steroids. Comparison of 3H- and 125I-ligands].
Characteristic properties of radioimmunoassay (RIA) of steroids with 3H- and 124I-ligands as a label were studied using two anabolic steroids methandrostenolone and 19-nortestosterone. Antisera towards 124I-steroids were used at higher dilutions as their specific activity was distinctly more than in the antisera to 3H-substances. However, 125I-steroid must be in a stereochemical correspondence with the antiserum otherwise antibodies do not bind the label. The antisera towards 3H-steroids were obtained after coupling of a carrier at any position of the steroid molecule. Standard curves for 3H-steroids were very steep; this pattern of the curves enabled to increase the accuracy of calculations. Sensitivity of RIA with 3H-label was also higher as compared with 125I-steroids in the experiments where unlabelled steroids inhibited the label binding with antibodies by 50%. Distinct differences were not observed in RIA specificity for methandrostenolone and 19-nortestosterone.


Emerging β-amyloid pathology and accelerated cortical atrophy.
The effect of β-amyloid (Aβ) accumulation on regional structural brain changes in early stages of Alzheimer disease (AD) is not well understood. To test the hypothesis that the development of Aβ pathology is related to increased regional atrophy in the brains of cognitively normal (CN) persons. Longitudinal clinicobiomarker cohort study involving 47 CN control subjects and 15 patients with AD dementia. All participants underwent repeated cerebrospinal fluid Aβ42 and structural magnetic resonance imaging measurements for up to 4 years. Cognitively normal controls were classified using the longitudinal cerebrospinal fluid Aβ42 data and included 13 stable Aβ negative (normal baseline Aβ42 levels, with less than the median reduction over time), 13 declining Aβ negative (normal baseline Aβ42 levels, with greater than the median reduction over time), and 21 Aβ positive (pathologic baseline Aβ42 levels). All 15 patients with AD dementia were Aβ positive. Group effects on regional gray matter volumes at baseline and over time, tested by linear mixed-effects models. Baseline gray matter volumes were similar among the CN Aβ groups, but atrophy rates were increased in frontoparietal regions in the declining Aβ-negative and Aβ-positive groups and in amygdala and temporal regions in the Aβ-positive group. Aβ-positive patients with AD dementia had further increased atrophy rates in hippocampus and temporal and cingulate regions. Emerging Aβ pathology is coupled to increased frontoparietal (but not temporal) atrophy rates. Atrophy rates peak early in frontoparietal regions but accelerate in hippocampus, temporal, and cingulate regions as the disease progresses to dementia. Early-stage Aβ pathology may have mild effects on local frontoparietal cortical integrity while effects in temporal regions appear later and accelerate, leading to the atrophy pattern typically seen in AD.


Detection of sentinel nodes by lymphoscintigraphy and gamma probe guided surgery in vulvar neoplasia.
Pathologic lymph node status is the most important prognostic factor in vulvar cancer; however, complete inguinofemoral node dissection is associated with significant morbidity. Intraoperative lymphoscintigraphy associated with gamma detecting probe-guided surgery has proved to be reliable in the detection of sentinel node (SN) involvement in melanoma and breast cancer patients. The present study evaluates the feasibility of the surgical identification of inguinal sentinel nodes using lymphoscintigraphy and a gamma detecting probe in patients with early vulvar cancer. Technetium-99-labeled colloid human albumin was administered perilesionally in 44 patients. Twenty patients had T1 and 23 had T2 invasive epidermoid vulvar cancer; one patient had a lower-third vaginal cancer. An intraoperative gamma detecting probe was used to identify SNs during surgery. Complete inguinofemoral node dissection was subsequently performed. SNs underwent separate pathologic evaluation. A total of 77 groins were dissected in 44 patients. SNs were identified in all the studied groins. Thirteen cases had positive nodes: the SN was positive in all of them; in 10 cases the SN was the only positive node. Thirty-one patients showed negative SNs: all of them were negative for lymph node metastasis. Lymphoscintigraphy and SN biopsy under gamma detecting probe guidance proved to be an easy and reliable method for detection of SNs in early vulvar cancer. If these preliminary data will be confirmed, the technique would represent a real progress towards less aggressive treatment in patients with vulvar cancer.


Polymer Photocatalysts Containing Segregated π-Conjugation Units with Electron-Trap Activity for Efficient Natural-light-driven Bacterial Inactivation.
Development of highly efficient and metal-free photocatalysts for bacterial inactivation under natural light is a major challenge in photocatalytic antibiosis. Herein, we developed an acidizing solvent-thermal approach for inserting a non-conjugated ethylenediamine segment into the conjugated planes of 3,4,9,10-perylene tetracarboxylic anhydride to generate a photocatalyst containing segregated π-conjugation units (EDA-PTCDA). Under natural light, EDA-PTCDA achieved 99.9 % inactivation of Escherichia coli and Staphylococcus aureus (60 and 45 min), which is the highest efficiency among all the natural light antibacterial reports. The difference in the surface potential and excited charge density corroborated the possibility of a built-in electron-trap effect of the non-conjugated segments of EDA-PTCDA, thus forming a highly active EDA-PTDA/bacteria interface. In addition, EDA-PTCDA exhibited negligible toxicity and damage to normal tissue cells. This catalyst provides a new opportunity for photocatalytic antibiosis under natural light conditions.


P1270Effects of blood pressure variability on layer-specific longitudinal strain in hypertension.
Our previous study showed sub-epicardial longitudinal strain (EpiLS) was an independent prognostic factor for worse outcome in regular treated hypertension but not global longitudinal strain (GLS) and sub-endocardial longitudinal strain (EndLS). Increased blood pressure variability (BPV) has been found associated with target organ damage in hypertension. However, effects of BPV on layer-specific longitudinal strain have not been well studied. The aim of this study was to investigate the effects of different blood pressure parameters on layer-specific longitudinal strain in hypertension. This study included 95 patients (57 men, age 65 ± 12 years) with uncomplicated hypertension who have been regularly treated for more than 1 year. Speckle tracking echocardiography was used for measurement of longitudinal deformation from 3 apical views of left ventricle. GLS was measured by automated function imaging (AFI). We further divided into sub-endocardial and sub-epicardial myocardium and measured their longitudinal strain by manual click-and-draw method and averaged from 3 apical views. Blood pressure parameters included office systolic blood pressure (SBP), office diastolic blood pressure (DBP), central SBP and DBP by tonometry, average 24-hour SBP and DBP, and BPV parameters by ambulatory blood pressure monitor. BPV parameters included standard deviation of daytime SBP (DSSD), standard deviation of nighttime SBP (NSSD), standard deviation of daytime DBP (DDSD), and standard deviation of nighttime DBP (NDSD). We divided subjects into low and high group according to median level of each strain. No blood pressure parameters were different between low and high EndLS group except week difference in NDSD (9.0 ± 3.4 vs. 7.8 ± 2.0 mmHg, p = 0.051). NSSD (11.2 ± 4.6 vs. 9.3 ± 2.9 mmHg, p = 0.027) and NDSD (9.1 ± 3.4 vs. 7.7 ± 2.0 mmHg, p = 0.031) were significant increased in low GLS group but not other parameters. DDSD (10.3 ± 3.0 vs. 9.0 ± 2.5 mmHg, p = 0.034), NSSD (11.4 ± 4.4 vs. 9.1 ± 3.1 mmHg, p = 0.006), and NDSD (9.2 ± 3.2 vs. 7.6 ± 2.2 mmHg, p = 0.012) were significantly increased in low EpiLS group. Only BPV parameters were associated with decreased longitudinal strain in hypertension. Effects of BPV were majorly noted in EpiLS.


[A predictive model of depression in rural elders-decision tree analysis].
This descriptive study was done to develop a predictive model of depression in rural elders that will guide prevention and reduction of depression in elders. A cross-sectional descriptive survey was done using face-to-face private interviews. Participants included in the final analysis were 461 elders (aged> or = 65 years). The questions were on depression, personal and environmental factors, body functions and structures, activity and participation. Decision tree analysis using the SPSS Modeler 14.1 program was applied to build an optimum and significant predictive model to predict depression in rural elders. From the data analysis, the predictive model for factors related to depression in rural elders presented with 4 path-ways. Predictive factors included exercise capacity, self-esteem, farming, social activity, cognitive function, and gender. The accuracy of the model was 83.7%, error rate 16.3%, sensitivity 63.3%, and specificity 93.6%. The results of this study can be used as a theoretical basis for developing a systematic knowledge system for nursing and for developing a protocol that prevents depression in elders living in rural areas, thereby contributing to advanced depression prevention for elders.


Through-wall electromagnetic scattering by N conducting cylinders.
A spectral-domain analysis is presented for the scattering by perfectly conducting cylindrical objects behind a dielectric wall. The solution is developed with an analytical-numerical technique, based on the cylindrical wave approach. Suitable cylindrical functions and their spectral representations are introduced as basis functions for the scattered fields, to deal with their interaction with the planar interfaces bounding the wall. The numerical solution is given in TE and TM polarizations states, and in both near- and far-field zones. The model yields an accurate computation of direct scattering that can be useful for through-wall-imaging applications. A stack of three different dielectric media is considered in the theoretical model. In the numerical results, the upper medium, where the incident field is generated, is assumed to be filled by air, the central layer represents the wall, and the lower medium, which contains the scatterers, is air filled, too. Also general problems of scattering by buried objects can be simulated, being the cylinders buried in a medium of arbitrary permittivity, placed below a dielectric layer.


[Re-restoration decisions].
In this study an attempt was made to explain some of the interobserver variation in re-restoration decision making using. A simplified re-restoration case was shown to 22 dentists who were asked what treatment decision they would make, and what factors would play a role in their decision. The treatment decisions were compared to the outcomes of a knowledge-system on re-restoration decision making. The dentists unanimously selected re-restoration as the treatment alternative. Half of the dentists preferred amalgam, and the other half chose composite as restorative material. This variation could be explained almost fully by the dentists' weighs on the factors 'tissue loss during preparation', 'restoration and preservation of the chewing function' and 'prognosis and durability of the restoration'. The knowledge system indicated that more than 80% of the dentists actually should have selected composite resin for a restorative material. It was concluded that the availability of knowledge and its application can explain variation in re-restoration decisions. Knowledge systems can be used in designing practice guidelines.


[Ultrastructural changes in the wall and microcirculatory bed of the small intestinal villi of rats exposed to organochlorine toxicant].
Male Wistar rats were administered 60 mg/kg of organochlorine pesticide 2,4-D daily (two permissible daily doses) for 2.5 months in order to develop an experimental model of chronic intoxication. It was found that the long term administration of organochlorine toxicant resulted in marked structural changes in both the cells of the wall of small intestine and in lymphatic and blood capillaries of the villi (distention of the rough endoplasmic reticulum cisterns, reduction of the number of mitochondrial christae, increase in the secondary lysosomal content, reduction of the number of micropinocytotic vesicles).


Humanistic, utilization, and cost outcomes associated with the use of botulinum toxin for treatment of refractory migraine headaches in a managed care organization.
Few patients with migraine syndrome receive treatment with preventive medication regimens, and some of these patients fail to gain adequate migraine relief. Botulinum toxin has been suggested to be effective in the treatment of migraine for a select population. An integrated health system created a medical policy and a supporting preauthorization form that permits coverage of botulinum toxin for the off-label treatment of migraine for patients who (1) fail at least 3 drug classes for acute treatment, (2) fail at least 4 different preventive medication classes, and (3) receive consultation from a neurologist. To (1) evaluate the impact of botulinum toxin therapy on quality-of-life (QOL) measures evaluated by direct member survey results, and (2) assess the use and cost of migraine-related medications and overall medical and pharmacy services pre- and post-botulinum toxin therapy. The study was a retrospective analysis of administrative claims data from a 500,000-member integrated health system for the time period January 1, 2003, to October 31, 2007. Administrative claims data were used to identify members with a billing code (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]) for migraine (346.xx), tension headache (307.81), or headache (784.0) diagnosed by a neurologist. Administrative claims data for these patients were then queried for the use of botulinum toxin for dates of service from January 1, 2003, through October 31, 2006. A survey was sent to the identified patients (N=54) to assess 6 QOL measures associated with the use of botulinum toxin. Self-reported symptomatic improvement was assessed using a 5-point Likert scale for 6 questions regarding headache severity, headache frequency, use of rescue medications, productivity/absenteeism, recreational activities, and life enjoyment. For the subset of patients (n = 32) who maintained health plan eligibility from 18 months before through 18 months after the first botulinum toxin therapy claim (index date), medical and pharmacy claims data were used to assess the utilization and cost of specific medications and overall pharmacy and medical costs for the 18-month pre-index and post-index periods. Cost was defined as allowed charge, which is the sum of plan cost and member cost. Of 54 surveys sent to all patients identified as having used botulinum toxin for the treatment of migraine from January 1, 2003, to October 31, 2006, 34 surveys were returned (63%). Almost 3 of 4 respondents (73%) reported moderate or better improvement in overall migraine or headache QOL measures, and 27% reported little or no improvement. For the 32 patients with continuous eligibility for the total observation period of 36 months, the average migraine-related pharmacy utilization, excluding botulinum toxin, increased by 50.5%, from 1.84 claims per patient per month (PPPM) in the 18-month pre-index period to 2.77 claims PPPM in the 18-month post-index period (P = 0.011) and by 59.5% by mean days supply (42.58 days to 67.93, P=0.008). Total migraine-related pharmacy cost increased by 80.9%, from $142.08 PPPM to $256.97 PPPM (P=0.013). Acute-treatment migraine-related pharmacy utilization increased from 1.23 claims PPPM to 1.92 claims PPPM (P=0.004). There was no significant change in either the number of claims for migraine prophylaxis medications (0.61 PPPM to 0.85 PPPM, P=0.121) or the use of hospital emergency room services related to migraine or headache (0.07 PPPM vs. 0.10 PPPM, P=0.449). The mean migraine-related and nonmigraine-related (i.e., all-cause) combined medical/hospital and pharmacy expense, including botulinum toxin, increased by 111.3%, from $651.13 PPPM in the pre-index period to $1,376.05 PPPM in the post-index period (P<0.001). The majority of patients who received botulinum toxin for refractory migraine reported improvement in disease-specific symptoms and overall QOL, but total medical and pharmacy costs were higher in the period after treatment, and there was no reduction in the use of other migraine-related medications.


High-dose immunoglobulin replacement therapy by slow subcutaneous infusion during pregnancy.
The slow, subcutaneous infusion method of immune human serum globulin replacement was used during pregnancy in a woman with common common variable immunodeficiency and splenectomy. Since this method allows high doses of immune human serum globulin to be given with little pain or morbidity, as much as 20 mL/day of immune human serum globulin was tolerated, normal serum IgG levels, were maintained, and the patient was free from serious infection throughout her pregnancy. The infant also had a normal IgG level at birth and had no evidence of intrauterine infection. This may be a preferable route of immune human serum globulin administration, especially during pregnancy and in other situations where high-dose therapy is advantageous.


[The clinical valency of monoclonal immunoglobulins. Attempt at a determination of their importance].
The classification of the protein bodies which Apitz in his time called paraproteins into the large spectre of the immunoglobulins has had a decisive influence on the clinical valency of these findings. Nowadays it is possible to estimate these proteins from the point of view of their development as the functional evidence of a monoclonal proliferation as well as issuing from the part of their immunological effect. 218 cases of monoclonal immunoglobulin are distributed according to the clinical diagnosis. Here it is shown that also a not unconsiderable proportion of benign diseases reveals these findings. Monoclonal immunoglobulins are of special interest when diseases of the group of nosological forms of the lympho-plasma-cellular reticulum and particularly of the paraproteinaemic haemoblastoses are in question. The analysis of the monoclonal macroglobulinaemias has led to a new orientation concerning Waldenstroem's disease which absolutely might be regarded as a nosological entity and no more as a morphological one. A special quality of the protein, the formation of cryoprotein, has close structural relations to the easy chain type kappa, which possibly in general must closely be correlated with reactions of immunoglobulins dependent on temperature.


Framing Effects of Cognitive Behavioural Therapy for Depression on Perceptions of Believability, Acceptability, and Credibility.
While CBT is an effective treatment for depression, uptake can be low. This is largely due to attitudinal barriers. Accordingly, the goals of the current investigation were to (a) tailor and develop persuasive psychoeducational materials to match dominant cultural beliefs about the causes of depression and (b) examine the effectiveness of tailored CBT descriptions in improving CBT perceptions. We examined the believability of CBT mechanisms by invoking commonly endorsed etiological models of depression and investigated whether tailoring CBT descriptions to match etiological beliefs about depression influences perceptions of CBT. Participants were recruited using TurkPrime. In Study 1, participants (n = 425) read a CBT description that was generic or framed to match an etiological model of depression (biological, stress/environmental, or relationship/interpersonal). The participants indicated believability of each model as adopted by CBT. In study 2, the participants (n = 449) selected what they believed was the most important cause of depression. Subsequently, the participants were randomised to receive either a CBT description tailored to their endorsed model or a generic CBT description, and they provided ratings for CBT's acceptability, credibility, and expectancy. In Study 1, the believability of biological CBT mechanisms was low across conditions, but participants reported greater believability when receiving a biological description than when receiving other mechanistic descriptions. Participants who received the stress- and relationship-focused descriptions did not rate the respective models as more believable than those who received a generic description. In study 2, there were no differences in the perceptions of acceptability, credibility and expectancy between participants who received a tailored description and those who received a generic description. Our findings suggest that CBT is believed to be a psychologically appropriate treatment; however, the believability of biological mechanisms is improved by presenting a biology-focused description.


Dental care for pregnant women: an assessment of North Carolina general dentists.
The authors conducted a study to examine factors associated with general dentists' provision of care for pregnant women and the extent to which they provide comprehensive dental care. The authors mailed an 86-item questionnaire to 1,000 practicing general dentists in North Carolina. Survey domains included provider knowledge about pregnancy and dental health, dental treatment practices, barriers to providing care, outcome expectancy, and personal and practice demographics. The primary dependent variables the authors analyzed were whether dentists provided any treatment to pregnant women and, among those who did, the extent to which they provided comprehensive services. The authors performed multivariate regression analyses to determine factors associated with dentists' provision of care to pregnant women (P < .05). A total of 513 surveys were returned (a response rate of 51.3 percent), of which 495 surveys had complete responses. The authors included the completed surveys in their analyses. The mean age of the respondents was 46 years. The results of multivariate analysis showed that respondents who perceived a lack of demand for services among pregnant women and provided preconception counseling were less likely to provide any treatment for pregnant patients than were those who perceived a demand for services and who did not provide preconception counseling, respectively. Dentists who were male, had a low knowledge score, provided preconception counseling and treated largely white populations of patients were less likely than female dentists, those who had moderate or high knowledge scores, and those who treated a population of minority patients to provide comprehensive care for pregnant women. Most general dentists in private practice provide care for pregnant women, but the authors found notable gaps in dental provider knowledge and comprehensive dental services available for pregnant women. Although many general dentists provide some dental care to pregnant women, more should be done to ensure that this care is comprehensive.


Effect of certain elicitors on production of pyrrolizidine alkaloids in hairy root cultures of Echium rauwolfii.
Hairy root cultures of Echium rauwolfii were obtained by infection of sterile apical shoots with Agrobacterium rhizogenes. The linear increase in fresh weight was found to be parallel to the alkaloids production. The transformed cultures were exposed to different elicitors, such as methyl jasmonate (MJ), quercetin and salicylic acid in order to increase their productivity. Pyrrolizidine alkaloids were quantitatively determined by HPLC. Estimation of total alkaloids was achieved by peak area calculations. MJ at a concentration of 100 microM induced the accumulation of total alkaloids about 19-fold compared to the untreated control. The flavonoid quercetin (Q) at a concentration of 50 microM enhanced the pyrrolizidine accumulation approximately 6-fold. The induction effect of both MJ and Q can be suppressed by pre-incubation of hairy root cultures with salicylic acid.


Eruptive histiocytoma of childhood.
A 9-year-old girl had a widespread papular eruption that was histologically characterized by benign histiocytes that were acid phosphatase-positive, but that lacked Langerhans' granules ultrastructurally. New lesions had continued to develop since the patient was 3 months old, and individual lesions had resolved over a period of two to three months. The histopathologic, histochemical, and ultrastructural findings in this patient were similar to those previously described for eruptive histiocytomas in adults. Papular histiocytomas in childhood may be found in histiocytosis X, reticulohistiocytoma, xanthogranuloma, xanthoma disseminatum, or eruptive histiocytoma. These diseases may be differentiated on the basis of differing histiocytic populations and the clinical courses of the lesions in each disorder.


Inositol-deficient food augments a behavioral effect of long-term lithium treatment mediated by inositol monophosphatase inhibition: an animal model with relevance for bipolar disorder.
Lithium treatment in rodents markedly enhances cholinergic agonists such as pilocarpine. This effect can be reversed in a stereospecific manner by administration of inositol, suggesting that the effect of lithium is caused by inositol monophosphatase inhibition and consequent inositol depletion. If so, inositol-deficient food would be expected to enhance lithium effects. Inositol-deficient food was prepared from inositol-free ingredients. Mice with a homozygote knockout of the inositol monophosphatase 1 gene unable to synthesize inositol endogenously and mimicking lithium-treated animals were fed this diet or a control diet. Lithium-treated wild-type animals were also treated with the inositol-deficient diet or control diet. Pilocarpine was administered after 1 week of treatment, and behavior including seizures was assessed using rating scale. Inositol-deficient food-treated animals, both lithium treated and with inositol monophosphatase 1 knockout, had significantly elevated cholinergic behavior rating and significantly increased or earlier seizures compared with the controls. The effect of inositol-deficient food supports the role of inositol depletion in the effects of lithium on pilocarpine-induced behavior. However, the relevance of this behavior to other more mood-related effects of lithium is not clear.


[The hypotensive effect of nitrogen oxide obtained from exogenous and endogenous sources].
Correlation was studied between content of nitrogen oxide, developed in rat tissues after administration of nitroprusside, nitroglycerol or Fe(2+)-citrate, and the rate of these agents hypotensive effect. Content of nitrogen oxide in tissues was measured using EPR procedure by calculation of paramagnetic mononitrosyl ferrum complexes and exogenous ligand sodium diethyl thiocarbamate. After administration of nitroprusside these complexes developed only within several minutes when the drug exhibited hypotensive effect on animals as a result of nitrogen oxide production. The correlation was not found for nitroglycerol effect due to low level of nitrogen oxide obtained from this drug. Administration of Fe(2+)-citrate enabled to detect the mononitrosyl ferrum-ligand complexes in liver tissue within 1 hr after termination of these complexes hypotensive effect.


Early detection and prediction of cardiotoxicity in chemotherapy-treated patients.
As breast cancer survival increases, cardiotoxicity associated with chemotherapeutic regimens such as anthracyclines and trastuzumab becomes a more significant issue. Assessment of the left ventricular (LV) ejection fraction fails to detect subtle alterations in LV function. The objective of this study was to evaluate whether more sensitive echocardiographic measurements and biomarkers could predict future cardiac dysfunction in chemotherapy-treated patients. Forty-three patients diagnosed with breast cancer who received anthracyclines and trastuzumab therapy underwent echocardiography and blood sampling at 3 time points (baseline and 3 and 6 months during the course of chemotherapy). The LV ejection fraction; peak systolic myocardial longitudinal, radial, and circumferential strain; echocardiographic markers of diastolic function; N-terminal pro-B-type natriuretic peptide; and high-sensitivity cardiac troponin I were measured. Nine patients (21%) developed cardiotoxicity (1 at 3 months and 8 at 6 months) as defined by the Cardiac Review and Evaluation Committee reviewing trastuzumab. A decrease in longitudinal strain from baseline to 3 months and detectable high-sensitivity cardiac troponin I at 3 months were independent predictors of the development of cardiotoxicity at 6 months. The LV ejection fraction, parameters of diastolic function, and N-terminal pro-B-type natriuretic peptide did not predict cardiotoxicity. In conclusion, cardiac troponin plasma concentrations and longitudinal strain predict the development of cardiotoxicity in patients treated with anthracyclines and trastuzumab. The 2 parameters may be useful to detect chemotherapy-treated patients who may benefit from alternative therapies, potentially decreasing the incidence of cardiotoxicity and its associated morbidity and mortality.


Comparison of visual results and optical quality of two presbyopia-correcting intraocular lenses: TECNIS symfony versus TECNIS synergy.
This study compared the extended depth of focus (EDOF) intraocular lens (IOL) (ZXR00; Tecnis® Symfony®, Johnson & Johnson Vision, Santa Ana, CA, USA) and a new presbyopia-correcting IOL that combines EDOF and multifocal profiles (ZFR00; Tecnis® Synergy®, Johnson & Johnson Vision, Santa Ana, CA, USA) with the same material. The medical records of patients undergoing cataract surgery with ZXR00 or ZFR00 implantation between March 2021 and July 2021 and with the data available for the 3-month visit were reviewed. The uncorrected near, intermediate, and distance visual acuity (VA), corrected distance VA, defocus curves, refractive errors (RE), optical quality parameters, and patient-reported visual performance parameters were the main outcome measures. Among the twenty-three enrolled patients, twelve patients (21 eyes) received ZXR00 and nine patients (17 eyes) received ZFR00. The mean age of the patients was 59.6 ± 10.6 (range: 49 to 70) and 65.2 ± 8.2 (range: 45 to 82) years in ZXR00 and ZFR00 groups, respectively, without significant difference. There was not a significant difference between the two groups in terms of baseline parameters and postoperative RE. The ZFR00 group showed markedly superior intermediate and near VA (p < 0.001 for all) at 3 months postoperatively. In terms of optical quality, ZXR00 was significantly better than ZFR00 (p < 0.001). Both IOLs had comparable distance VA. ZFR00 IOL was superior for intermediate and near visual acuity, but ZXR00 IOL was better for optical quality. Research with more participants is needed to support this finding.


Annular pancreas: dramatic differences between children and adults.
Annular pancreas is rare; only 737 cases have been reported in the English literature. In addition, no large analysis has compared children and adults. Recently, prenatal diagnosis and advances in imaging have led to increased experience with this condition. Data from 103 patients (48 children, 55 adults) with annular pancreas, managed from 1992 to 2006, were reviewed. Patients with isolated duodenal atresia, stenosis, or webs were excluded. Median ages at diagnosis were 1 day in children and 47 years in adults. Annular pancreas was more common in girls and women (children, 58%; adults, 69%). Congenital anomalies were more frequent (p < 0.01) in children (71%) than in adults (16%); Down syndrome, cardiac, and intestinal anomalies were most common. Prenatal diagnosis was suspected in 56% of infants, and adults presented with pain (75%), vomiting (24%), pancreatitis (22%), or abnormal liver tests (11%). All children were managed with duodenal bypass. Children were more likely (p < 0.01) to require surgery for associated anomalies. In contrast, adults had fewer duodenal bypass procedures (24%) but more often required endoscopic pancreatobiliary procedures (67%), cholecystectomy (56%), and other pancreatobiliary surgery (20%; p < 0.01). Adults more commonly (p < 0.01) had pancreas divisum (29%) and pancreatobiliary neoplasia (11%). Five children (6%) with multiple anomalies died; all adults survived their operations. Late deaths occurred in 2 children (4%) with multiple anomalies and 3 adults (5%) with pancreatobiliary cancer. Annular pancreas is associated with a spectrum of disease that differs in children and adults. Congenital anomalies are more common in children with annular pancreas; complex pancreatobiliary disorders and malignancy are more frequent in adults.


Associations of Medication Regimen Complexity with COPD Medication Adherence and Control.
Medication adherence is often low among people with chronic obstructive pulmonary disease (COPD) and medication regimen complexity may be a contributing factor. In this study, we sought to examine the role of medication regimen complexity in COPD medication adherence among patients with multimorbidity. We performed cross-sectional analysis of data on COPD patients in primary care and pulmonary practices in New York City and Chicago (n=400). Regimen complexity was represented by the medication regimen complexity index (MRCI) and simple medication count. Adherence was measured by self-report and inhaler dose counts. Disease control measures included the COPD severity score (COPDSS) and the Medical Research Council (MRC) severity index. Mean age of study participants was 69 years, 66% had MRC grades 4 or 5, and 45% had low medication adherence. MRCI scores did not differ significantly between those with and without adequate medication adherence. Patients with higher MRCI scores were more likely to have severe COPD (OR 5.00, 95% CI 1.46-17.1, p=0.01) and dyspnea grades 3 or 4 (OR 2.27, 95% CI 1.03-5.03, p=0.04). Significant associations of medication count with COPD severity were also observed. These findings demonstrate that among patients with COPD and comorbid hypertension and diabetes, higher medication regimen complexity is associated with worse COPD control but not with COPD medication adherence.


[Mastitis by Aspergillus fumigatus in sheep].
Several outbreaks of sheep mastitis by Aspergillus fumigatus in Castilla y Leon (Spain), were studied. Only sheep that were treated intramammarily with antibacterial antibiotics during the dry period suffered this mastitis. Mastitis was acute with a morbidity up to 14 % and mortality near 100 %. The udder was markedly enlarged in size, fibrotic, haemorrhagic and with multiple compact nodules, some with purulent material inside; after 30-50 days postpartum, cheesy abscess of several centimetres in diameter were present. Some sheep had granulomatous nodules in the lung. Microscopy and culture shown the presence of A. fumigatus in milk, udder and lung. The route of infection was by intramammary via as a consequence of unhygienic intramammary treatment in the dry period.


[Turner's syndrome. Relationship between the karyotypes and malformations and associated diseases in 23 patients].
In this study we have assessed the frequency of karyotypes, phenotypes and some associated diseases 23 girls affected with turner's syndrome. Moreover, we have analyzed their relationships. The most important findings the following: 1) The mean age at diagnosis was 7.37 +/- 5.65 (0, 16) years. 2) The most frequent karyotype was monosomy 45XO, which was found in fourteen patients (60.9%), followed by isochromosome of the long arm of chromosome 46 XiXq in five cases (21.7%), two mosaics, one 45 XO/46 XiXq and one 45XO/46XX, and two deletions of the short arm of chromosome X (46 XX Xp-). 3) The classical phenotype was found in 87% of the cases. 4) Bone malformations were found in nine patients (39.1%). The most frequent were, short metacarpals in five cases, knee anomalies (Kosowicz's sign) in four, one Madelung deformity and one alata scapula. 5) Renal malformations were detected in five patients (21.8%), two rotational abnormalities, two horseshoe kidneys and one double collecting system. 6) Cardiovascular malformations were found in four cases (17.3%). Three bicuspid aortic valves and one aortic coarctation were diagnosed. 7) Otitis media was discovered in seven girls (30.5%). 8) Other processes found were, congenital lymphedema in four cases, one Klipell-Trenaunay syndrome, one Dandy-Walker anomaly, one congenital glaucoma, one colesteatoma, one congenital torticolis, one hit luxation and one essential arterial hypertension. A significant correlation was found between karyotype and phenotype, such that all of the patients with monosomies and with mosaics, 66% of those with X isochromosomes and one of the patients with a deletion had a classical phenotype. We found no correlation between the karyotype and the different malformations and associated diseases.


Improved population level survival in younger Hodgkin lymphoma patients in Germany in the early 21st century.
Treatment for Hodgkin lymphoma (HL) is more aggressive in Germany than in the United States (US) and differences in treatment may lead to differences in population level survival. Patients diagnosed with HL in 11 German states in 1997-2006 were included in the analyses and were compared to similar analyses from patients in the Surveillance, Epidemiology, and End Results database in the US. Period analysis was used to calculate 5-year relative survival for the time period of 2002-2006 overall and by gender, age and histology. Overall 5-year relative survival for patients with HL in Germany was 84·3%, compared to 80·6% for the US. Survival was highest in patients aged 15-29 years at 97·9% and decreased with age to 57·5% at age 60 + Survival for men and women, respectively, was 84·7% and 84·1% in Germany and 78·2% and 83·6% in the US. 5-year relative survival for patients diagnosed with HL in Germany was close to 100% for younger patients. Survival of HL patients in the US was lower than in Germany overall, but was comparable in older patients and in women. Population-based studies with longer follow-up are still needed to examine effects of late toxicity on long term survival.


Reducing distress in first level and student nurses: a review of the applied stress management literature.
Following recent evidence of continuing high levels of distress in both trained and student nurses, a critical review of the stress reduction and stress management literature targeting both trained and student nurses is presented. Using a systematic approach, some 36 studies dating from 1980 until the present day were identified adopting either pre-experimental, quasi-experimental or experimental designs. While many work-site programmes in this series were successful in terms of adaptive changes in problem-solving, self-management skills including relaxation and interpersonal skills, affective well-being, and work performance, a number of design and evaluation inadequacies were identified. The relative lack of home-work interface or organizational level programmes to reduce work-related distress, and the scarcity of interventions targeting aspects of the work environment likely to contribute to such outcomes may have contributed to continuing high levels of distress in trained and student nurses. Recommendations regarding the future design, provision and evaluation of such work-site interventions include the further clarification of the structure of perceived stressors, and development of causal models of the stress process to identify the job characteristics 'causing' work-related distress. Such an approach would inform the design and implementation of evidence-based organizational level interventions augmenting strategies to target the health behaviour, lifestyle/risk factors and self-management skills of practitioners and students with attempts to amend problematic elements of the psychosocial work environment.


Atrial Myxoma Mimicking Mitral Stenosis.
Myxoma is the most common primary cardiac tumor and is usually located in the left atrium. Clinical manifestation relies in large part on the size, location, and architecture of the tumor. There are many reports in the literature of cardiac myxomas causing syncope, embolism, even myocardial infarction. We present a rare case of a patient who underwent urgent surgical resection of a large left atrial myxoma mimicking mitral stenosis. The postoperative course of the patient was uncomplicated. One year after surgery, the patient is asymptomatic and disease-free.


Season by genotype interaction related to broiler growth rate and heat tolerance.
A study was conducted to evaluate the effect of genotype by environment (G x E) interaction on the performance of commercial broilers. Temperate and hot environments were established by making use of the natural climatic differences between spring and summer in western Turkey. The experimental population was produced by a full-pedigree, randomly assigned mating scheme consisting of 29 sires and five dams per sire. The sires were considered genotypes, and the G x E interaction was evaluated by regressing sire breeding values in summer on those estimated from their spring offspring. The correlation between the two seasons for weight gain from 0 to 4 wk of age was r = 0.26, significantly lower than rho = 1 (the expectation when there is no G x E interaction). This correlation was even negative (although not significantly lower than rho = 0) for weight gain (WG) from 4 to 7 wk of age and BW at 7 wk of age. Genotype by season ANOVA also revealed highly significant G x E interaction effects on all traits. These interactions suggest the presence of substantial genetic variation in the magnitude of heat tolerance. It appeared that this variation was not random, but rather related to growth potential, where genotypes that gain more weight in the spring tended to gain less weight under the hot conditions of summer.


[The understanding of users of a Family Health Unit about the pap smear test].
In the attempt to prevent cervical cancer, various preventive measures have been instituted, notable among which is the pap smear test, which fulfills the function of early detection of cancer cells or their precursors. Therefore, the objective was to investigate the discourse on the knowledge, feelings and expectations of women regarding the pap smear test. This is an exploratory qualitative approach, conducted with ten users of a Integrated Family Health Unit in the city of João Pessoa in the State of Paraíba. Data collection was conducted through recorded interviews in April 2011. Eight core ideas were identified: prevention of disease; self-motivated search, search recommended by another person; sense of shame and embarrassment, sensation of pain, feeling of satisfaction; conversations during the examination and exchange of knowledge about women's health. Based on the reports, there are many difficulties to be overcome to ensure greater adherence of women to the pap smear test.


Changing partners in the dark: isotopic and molecular evidence of ectomycorrhizal liaisons between forest orchids and trees.
In the mycorrhizal symbiosis, plants exchange photosynthates for mineral nutrients acquired by fungi from the soil. This mutualistic arrangement has been subverted by hundreds of mycorrhizal plant species that lack the ability to photosynthesize. The most numerous examples of this behaviour are found in the largest plant family, the Orchidaceae. Although these non-photosynthetic orchid species are known to be highly specialized exploiters of the ectomycorrhizal symbiosis, photosynthetic orchids are thought to use free-living saprophytic, or pathogenic, fungal lineages. However, we present evidence that putatively photosynthetic orchids from five species which grow in the understorey of forests: (i) form mycorrhizas with ectomycorrhizal fungi of forest trees; and (ii) have stable isotope signatures indicating distinctive pathways for nitrogen and carbon acquisition approaching those of non-photosynthetic orchids that associate with ectomycorrhizal fungi of forest trees. These findings represent a major shift in our understanding of both orchid ecology and evolution because they explain how orchids can thrive in low-irradiance niches and they show that a shift to exploiting ectomycorrhizal fungi precedes viable losses of photosynthetic ability in orchid lineages.


Prospects for developing allergen-depleted food crops.
In addition to the challenge of meeting global demand for food production, there are increasing concerns about food safety and the need to protect consumer health from the negative effects of foodborne allergies. Certain bio-molecules (usually proteins) present in food can act as allergens that trigger unusual immunological reactions, with potentially life-threatening consequences. The relentless working lifestyles of the modern era often incorporate poor eating habits that include readymade prepackaged and processed foods, which contain additives such as peanuts, tree nuts, wheat, and soy-based products, rather than traditional home cooking. Of the predominant allergenic foods (soybean, wheat, fish, peanut, shellfish, tree nuts, eggs, and milk), peanuts (Arachis hypogaea) are the best characterized source of allergens, followed by tree nuts (Juglans regia, Prunus amygdalus, Corylus avellana, Carya illinoinensis, Anacardium occidentale, Pistacia vera, Bertholletia excels), wheat (Triticum aestivum), soybeans (Glycine max), and kidney beans (Phaseolus vulgaris). The prevalence of food allergies has risen significantly in recent years including chance of accidental exposure to such foods. In contrast, the standards of detection, diagnosis, and cure have not kept pace and unfortunately are often suboptimal. In this review, we mainly focus on the prevalence of allergies associated with peanut, tree nuts, wheat, soybean, and kidney bean, highlighting their physiological properties and functions as well as considering research directions for tailoring allergen gene expression. In particular, we discuss how recent advances in molecular breeding, genetic engineering, and genome editing can be used to develop potential low allergen food crops that protect consumer health.


Microsurgical training model with nonliving swine head. Alternative for neurosurgical education.
This paper proposes a practical model of microneurosurgical training using a nonliving swine head. Fresh porcine heads were obtained from butchery and dissected at our Laboratory of Microsurgery. Brain and skull base surgery were trained under microscopic magnification. Several neurosurgical procedures could be simulated in the nonliving pig model, including transcallosal approach to the lateral ventricle, lateral sulcus and middle fossa dissection, and posterior fossa surgery. The swine model perfectly simulates standard microneurosurgical procedures, and is a useful tool for developing and refining surgical skills.


Synthesis of a putative subtype specific antigenic heptapeptide from Escherichia coli K88 ad protein fimbriae.
The heptapeptide methyl ester Phe-Asn-Glu-Asn-Met-Ala-Tyr-OMe covering the amino acid sequence of the region 213-219 of Escherichia Coli K88 ad protein fimbriae is synthesized using N alpha-t-butyloxycarbonyl-protection and benzyl groups for side-chain-protection. All condensation reactions are performed in 84-97% yield by preactivation of the protected amino acids by dicyclohexylcarbodiimide (DCC) and 1-hydroxybenzotriazole (HOBt), and reaction of the resulting active ester with amine in the presence of 4-methylmorpholine (NMM). A mechanism is proposed for the nitrile formation in the side-chain of activated asparagine, and the suppression of this side-reaction is investigated. The repetitive deprotection is performed in a mixture of trifluoroacetic acid (TFA), phenol and p-cresol to give the TFA salts in virtually quantitatively yields. The final deprotection of the heptapeptide is carried out in a mixture of 25% hydrogen fluoride (HF) and dimethyl sulfide (DMS) in an overall yield of 48%. The serological and conformational properties of the synthetic peptide are under investigation.


Clinical findings using ingenol mebutate gel to treat actinic keratoses.
Actinic keratosis (AK) is a common ultraviolet light-induced skin lesion found on sun-exposed skin areas generally in older, fair-skinned people. It is part of a disease continuum observed in photodamaged skin that may lead to invasive squamous cell carcinoma. The presence of AK is associated with an increased risk of all skin cancers, as it is visible evidence of the carcinogenic effects of cumulative ultraviolet exposure. AKs are treated with lesion- and field-directed methods. Field-directed methods treat both the visible and subclinical lesions present in photodamaged skin, but treatment regimens are often lengthy and associated with poor tolerability because of vigorous local inflammatory reactions. Ingenol mebutate gel was recently approved by the Food and Drug Administration for topical treatment of AK. It induces cell death preferentially in transformed keratinocytes and promotes an inflammatory response that kills remaining tumor cells. In human studies, ingenol mebutate achieved high clearance rates of AK on the trunk or extremities and face or scalp after once-daily application for 2 or 3 consecutive daily treatments, when measured by complete or partial clearance of lesions. The localized inflammatory skin responses were generally mild to moderate and resolved in approximately 2 weeks on the face or scalp and 4 weeks on the trunk or extremities.


Resolving the role of plant glutamate dehydrogenase: II. Physiological characterization of plants overexpressing the two enzyme subunits individually or simultaneously.
Glutamate dehydrogenase (GDH; EC 184.108.40.206) is able to carry out the deamination of glutamate in higher plants. In order to obtain a better understanding of the physiological function of GDH in leaves, transgenic tobacco (Nicotiana tabacum L.) plants were constructed that overexpress two genes from Nicotiana plumbaginifolia (GDHA and GDHB under the control of the Cauliflower mosiac virus 35S promoter), which encode the α- and β-subunits of GDH individually or simultaneously. In the transgenic plants, the GDH protein accumulated in the mitochondria of mesophyll cells and in the mitochondria of the phloem companion cells (CCs), where the native enzyme is normally expressed. Such a shift in the cellular location of the GDH enzyme induced major changes in carbon and nitrogen metabolite accumulation and a reduction in growth. These changes were mainly characterized by a decrease in the amount of sucrose, starch and glutamine in the leaves, which was accompanied by an increase in the amount of nitrate and Chl. In addition, there was an increase in the content of asparagine and a decrease in proline. Such changes may explain the lower plant biomass determined in the GDH-overexpressing lines. Overexpressing the two genes GDHA and GDHB individually or simultaneously induced a differential accumulation of glutamate and glutamine and a modification of the glutamate to glutamine ratio. The impact of the metabolic changes occurring in the different types of GDH-overexpressing plants is discussed in relation to the possible physiological function of each subunit when present in the form of homohexamers or heterohexamers.


Insomnia and its correlates in a representative sample of the Greek population.
Insomnia is a major public health concern affecting about 10% of the general population in its chronic form. Furthermore, epidemiological surveys demonstrate that poor sleep and sleep dissatisfaction are even more frequent problems (10-48%) in the community. This is the first report on the prevalence of insomnia in Greece, a southeastern European country which differs in several socio-cultural and climatic aspects from the rest of European Community members. Data obtained from a national household survey (n = 1005) were used to assess the relationship between insomnia symptoms and a variety of sociodemographic variables, life habits, and health-related factors. A self-administered questionnaire with questions pertaining to general health and related issues was given to the participants. The Short Form-36 (Mental Health subscale), the Athens Insomnia Scale (AIS) as a measure of insomnia-related symptoms, and the International Physical Activity Questionnaire (IPAQ) were also used for the assessment. The prevalence of insomnia in the total sample was 25.3% (n = 254); insomnia was more frequent in women than men (30.7% vs. 19.5%) and increased with age. Multiple regression analysis revealed a significant association of insomnia with low socio-economical status and educational level, physical inactivity, existence of a chronic physical or mental disease and increased number of hospitalizations in the previous year. The present study confirms most findings reported from other developed countries around the world regarding the high prevalence of insomnia problems in the general population and their association with several sociodemographic and health-related predisposing factors. These results further indicate the need for more active interventions on the part of physicians who should suspect and specifically ask about such symptoms.


Changes in peroxisome proliferator-activated receptor gamma gene expression of chicken abdominal adipose tissue with different age, sex and genotype.
Peroxisome proliferatior-activated receptor gamma (PPARgamma) is a transcription factor that regulates adipocyte differentiation, and the activation of PPARgamma increases fat deposition in growing chickens. The aim of the present study was to investigate whether the levels of PPARgamma gene expression were related to fat pad weight in abdominal adipose tissue in growing chickens with different genotype and sex. Body weight and abdominal adipose tissue weight in broiler chickens (Ross strain) were higher than the other genotypes (Road Island Red, White Leghorn, and Japanese native poultry (Tsushima)) at 3 and 5 weeks of age. PPARgamma mRNA expression in abdominal adipose tissue tended to increase with age, as evidenced by higher expression levels at 5 weeks than at 1 week of age in all sex and genotype of chickens. In broiler chickens, the PPARgamma expressions were significantly higher than the other genotypes. PPARgamma mRNA expression levels in abdominal adipose tissue of female chickens rapidly increased at 3 weeks, and were unchanged until 5 weeks, while those in male chickens gradually increased until 5 weeks. In addition, abdominal adipose tissue weight was correlated with PPARgamma expression levels. These results demonstrated that PPARgamma gene expression is a useful marker of fat deposition in chickens, suggesting that PPARgamma is a key factor of fat accumulation in chicken abdominal fat pad.


The use of supportive communication when responding to older people's emotional distress in home care - An observational study.
Responding to older people's distress by acknowledging or encouraging further discussion of emotions is central to supportive, person-centred communication, and may enhance home care outcomes and thereby promote healthy aging. This observational study describes nursing staff's responses to older people's emotional distress, and identify factors that encourage further emotional disclosure. Audio-recorded home care visits in Norway (n = 196), including 48 older people and 33 nursing staff, were analysed with the Verona Coding Definitions of Emotional Sequences, identifying expressions of emotional distress and subsequent provider responses. The inter-rater reliability (two coders), Cohen's kappa, was >0.6. Sum categories of emotional distress were constructed: a) verbal and non-verbal expressions referring to emotion, b) references to unpleasant states/circumstances, and c) contextual hints of emotion. A binary variable was constructed based on the VR response codes, differentiating between emotion-focused responses and responses that distanced emotion. Fisher's exact test was used to analyse group differences and determined variables included in a multivariate logistic regression analysis to identify factors promoting emotion-focused responses. Older people's expressions of emotional distress (n = 635) comprised 63 explicit concerns and 572 cues. Forty-eight per cent of nursing staff responses (n = 638) were emotion-focused. Emotion-focused responses were observed more frequently when nursing staff elicited the expression of emotional distress from the patients (54%) than when patients expressed their emotional distress on their own initiative (39%). Expressions with reference to emotion most often received emotion-focused responses (60%), whereas references to unpleasant states or circumstances and contextual hints of emotion most often received non-emotion-focused responses (59%). In a multivariate logistic model, nursing staff's elicitation of the emotional expression (vs patients initiating it) and patients' expression with a reference to an emotion (vs reference to unpleasant states or contextual hints) were both explanatory variables for emotion-focused responses. Emotion-focused responses were promoted when nursing staff elicited the emotional expression, and when the patient expression referred to an emotion. Staff responded most often by acknowledging the distress and using moderately person-centred supportive communication. More research is needed to establish generalizability of the findings and whether older people deem such responses supportive.


Global scenarios of resource and emission savings from material efficiency in residential buildings and cars.
Material production accounts for a quarter of global greenhouse gas (GHG) emissions. Resource-efficiency and circular-economy strategies, both industry and demand-focused, promise emission reductions through reducing material use, but detailed assessments of their GHG reduction potential are lacking. We present a global-scale analysis of material efficiency for passenger vehicles and residential buildings. We estimate future changes in material flows and energy use due to increased yields, light design, material substitution, extended service life, and increased service efficiency, reuse, and recycling. Together, these strategies can reduce cumulative global GHG emissions until 2050 by 20-52 Gt CO2-eq (residential buildings) and 13-26 Gt CO2e-eq (passenger vehicles), depending on policy assumptions. Next to energy efficiency and low-carbon energy supply, material efficiency is the third pillar of deep decarbonization for these sectors. For residential buildings, wood construction and reduced floorspace show the highest potential. For passenger vehicles, it is ride sharing and car sharing.


Somatosensory input to non-primary motor areas is enhanced during preparation of cued contraterlateral finger sequence movements.
Frontal N30 somatosensory evoked potentials (SEPs) represent early somatosensory input into non-primary motor areas. Importantly, modulations of frontal N30 SEPs can provide insight into the mechanisms involved in sensory processing for movement control. Enhancements of frontal N30 SEPs have been revealed during repetitive but not during the preparation of movements that are contralateral to median nerve (MN) stimulation (i.e. contralateral movements). Importantly, these enhancements during contralateral movements may be dependent on increased activity in several neural areas such as the primary motor cortex (M1), supplementary motor area (SMA) and basal ganglia (BG). Furthermore, research has also shown that patients with prefrontal lesions have enhanced early frontal SEPs (i.e. N28) at rest supporting a role of the prefrontal cortex in inhibitory modulation of early somatosensory input. The current study evaluated whether differential modulations of frontal N30 SEPs occurred during different time periods when individuals prepared and executed contralateral (right) finger sequences to attended vibrotactile (VibT) stimuli at the left index finger. SEPs were measured to median nerve (MN) stimuli elicited at the left wrist and MN stimuli were time-locked in four different periods relative to VibT onset (during pre-stimulus, early response preparation, late movement preparation and movement execution). Results revealed that frontal N30 SEPs were significantly enhanced when MN stimulation occurred in the late preparatory and/or early movement execution period (∼750 ms) after the attended VibT stimuli. This result supports that increases in frontal N30 amplitudes during contralateral movements are dependent on the complexity of preparing and executing finger sequences, which is associated with increased activity in several neural areas such as the non-primary motor areas, prefrontal cortex and BG. Furthermore, enhanced N30 SEPs during contralateral movement preparation and execution may be a necessary mechanism to decrease sensory gating to facilitate somatosensory processing in non-primary motor areas when there is a 'noisy' environment.


So I thought I wanted to be a chief.
In July 2000, Dr. William Hazzard published an article in the Journal of the American Geriatrics Society entitled "So you think you want to lead an academic geriatric program?" My answer to that question the same month was "Yes," as I agreed to become the chief of the newly established Section of Geriatrics at the University of Chicago. With about 3.5 years on the job now, I offer a more complete reply to Dr. Hazzard's query. Although his paper covered many important and practical issues to consider in looking at becoming a chief, this article provides a perspective on the academic geriatric leadership position based on a new chief's observations. Topics covered include pressures for and against becoming a chief, changing perspectives on goals and rewards, good help, mentoring, money problems/issues, support for the chief, and communication and relationships. It is hoped that these observations will be of use to geriatricians considering leading an academic geriatrics program and to other newly appointed chiefs.


Relation between clopidogrel active metabolite levels and different platelet aggregation methods in patients receiving clopidogrel and aspirin.
Clopidogrel is a prodrug that undergoes bioconversion via cytochrome P450 system to form an active metabolite (AM) that binds to the platelet ADP receptor. The antiplatelet effect of clopidogrel is commonly assessed by measuring the aggregatory response to 5 μM ADP by light transmission aggregation (LTA) or multiple electrode aggregometry (MEA) or by the vasodilator-stimulated phosphoprotein platelet reactivity index (VASP-PRI). To determine which of these three tests of platelet ADP receptor pathway inhibition most closely correlates with clopidogrel AM levels. We analyzed blood samples from 82 patients with coronary artery disease who were randomized to receive double-dose or standard dose clopidogrel for 2 weeks. We measured peak clopidogrel AM levels, platelet aggregation in response to ADP and VASP-PRI on days 1, and repeated all the measures on days 7 and 14. Linear regression analysis was used to examine the correlation between clopidogrel AM and LTA, MEA and VASP-PRI. Bland-Altman plots were used to explore the agreement between tests of the antiplatelet effects of clopidogrel. Clopidogrel AM on day 1 correlated most closely with VASP-PRI (r = -0.5767) and demonstrated weaker correlations with LTA (r = -0.4656) and MEA (r = -0.3384) (all p < 0.01). Intra-class correlation (ICC) between VASP-PRI and LTA was 0.6446; VASP-PRI and MEA was 0.4720; and LTA and MEA was 0.4693. Similar results were obtained on days 7 and 14. Commonly used pharmacodynamic measures of clopidogrel response are only moderately correlated with clopidogrel AM levels and may not be suitable to measure the adequacy of clopidogrel therapy.


Folate and colorectal neoplasia: relation between plasma and dietary markers of folate and adenoma recurrence.
The results of epidemiologic studies indicate that higher intakes or blood concentrations of folate are associated with a lower risk of colorectal neoplasia; however, only one study assessed the role of homocysteine. We assessed the relation between biochemical and dietary markers of folate status and colorectal adenoma recurrence. Analyses were conducted in 1014 men and women aged 40-80 y who had undergone removal of all colorectal polyps. Diet and supplement use were ascertained through a food-frequency questionnaire administered at study entry. Blood collected at baseline was used to measure plasma folate and homocysteine concentrations. Unconditional logistic regression was used to assess the odds of recurrence associated with the intakes of folate, methionine, and vitamins B-6 and B-12 and with plasma folate and homocysteine. Relative to subjects in the highest quartile of plasma homocysteine, those in the lowest quartile had an odds ratio (OR) of adenoma recurrence of 0.69 (95% CI: 0.47, 1.02; P for trend = 0.02) after adjustment for confounding factors. Lower odds of recurrence were shown for higher plasma folate (OR: 0.66; 95% CI: 0.46, 0.97) and higher total intakes (dietary plus supplemental) of folate (OR: 0.61; 0.42, 0.89) and vitamin B-6 (OR: 0.65; 0.45, 0.94). Slightly weaker and nonsignificant associations were shown for dietary folate, methionine, and total vitamin B-12. A lower recurrence of colorectal adenomas was shown in subjects with higher intakes and plasma concentrations of folate. Additional markers involved in folate metabolism, including lower homocysteine and higher vitamin B-6 intake, were also associated with lower odds of recurrence.


Moving towards organised care of chronic disease. The 3+ visit plan.
The health care system is better organised to react to acute rather than chronic presentations of disease, yet a significant proportion of health care expenditure is on chronic diseases and their complications. This article seeks to argue the case for the organised care of chronic disease. Asthma is used as the demonstration disease because a model has already been developed and a pilot evaluation has been done. The National Asthma Campaign has been involved in the development, by general practitioners, of a system of asthma care organised in a way appropriate for general practice in Australia. The care is provided over a series of visits and ensures that all of the six steps of the Asthma Management Plan are covered.


Crystal structure of the archaeal holliday junction resolvase Hjc and implications for DNA recognition.
Homologous recombination is a crucial mechanism in determining genetic diversity and repairing damaged chromosomes. Holliday junction is the universal DNA intermediate whose interaction with proteins is one of the major events in the recombinational process. Hjc is an archaeal endonuclease, which specifically resolves the junction DNA to produce two separate recombinant DNA duplexes. The atomic structure of Hjc should clarify the mechanisms of the specific recognition with Holliday junction and the catalytic reaction. The crystal structure of Hjc from the hyperthermophilic archaeon Pyrococcus furiosus has been determined at 2.0 A resolution. The active Hjc molecule forms a homodimer, where an extensive hydrophobic interface tightly assembles two subunits of a single compact domain. The folding of the Hjc subunit is clearly different from any other Holliday junction resolvases thus far known. Instead, it resembles those of type II restriction endonucleases, including the configurations of the active site residues, which constitute the canonical catalytic motifs. The dimeric Hjc molecule displays an extensive basic surface on one side, which contains many conserved amino acids, including those in the active site. The architectural similarity of Hjc to restriction endonucleases allowed us to construct a putative model of the complex with Holliday junction. This model accounts for how Hjc recognizes and resolves the junction DNA in a specific manner. Mutational and biochemical analyses highlight the importance of some loops and the amino terminal region in interaction with DNA.