Transrectal US of the seminal vesicles and ejaculatory ducts: clinical correlation.
Transrectal ultrasonography (US) provides excellent anatomic detail of pathologic changes in the seminal vesicles and ejaculatory ducts. Fifty-two patients with US findings of seminal vesicle dilatation or cysts, ejaculatory duct cysts, or seminal vesicle or ejaculatory duct calculi were given questionnaires concerning a broad spectrum of genito-urinary symptoms. Compared with age-matched controls with normal US findings, patients with calculi in the seminal vesicles or ejaculatory ducts had a significantly increased prevalence of hematospermia and ejaculatory pain (P less than .01), and patients with cystic dilatation of the seminal vesicles were more likely to have perineal pain. Large midline cysts containing calculi or debris were symptomatic and probably represent müllerian duct remnants. Small cysts of the ejaculatory ducts were asymptomatic. Transrectal US may provide clinical insight into the causes of significant genitourinary symptoms that may previously have been ascribed to chronic nonbacterial prostatitis or have been considered to be idiopathic.


Neuropsychological dysfunction among affected heterozygous fragile X females.
Fragile X (or Martin-Bell) syndrome is an X-linked disorder that often produces mental retardation in males, but usually affects heterozygous females to a lesser degree. Here we report the results of a brief neuropsychological examination of 20 heterozygous fra(x) girls and women and two control groups of 20 individuals each. One control group was composed of fra(x)-negative mothers (obligate carriers) and sisters of male probands with fra(x) syndrome, whereas the other was composed of 14 head-injured and six learning disabled women and girls. In addition to general intellectual impairment, several specific cognitive deficits were consistently found in individuals with the Martin-Bell syndrome, suggesting focal neuropsychological dysfunction. Significant differences were noted between fra(x) individuals and controls on most cognitive and neuropsychological measures studied. Over one-third of the fra(x) individuals demonstrated neuropsychological symptoms characteristic of the full developmental Gerstmann syndrome, whereas another third had three or four of the five signs of possible parietal lobe dysfunction. In our sample, there was an association between improved performance and increasing age. Differences among heterozygous individuals in number of focal symptoms may reflect some variability in the penetrance of the fra(x) gene, as well as in the functional organization of the brain.


Prospective study of carmustine wafers in combination with 6-month metronomic temozolomide and radiation therapy in newly diagnosed glioblastoma: preliminary results.
Locoregional chemotherapy with carmustine wafers, positioned at surgery and followed by radiation therapy, has been shown to prolong survival in patients with newly diagnosed glioblastoma, as has concomitant radiochemotherapy with temozolomide. A combination of carmustine wafers with the Stupp treatment regimen has only been investigated in retrospective studies. In a single-institution prospective study, the authors assessed 12-month progression-free survival (PFS), toxicity, and overall survival in patients with glioblastoma treated with surgery, carmustine wafers, radiotherapy, and 6-month metronomic temozolomide chemotherapy. Thirty-five patients with de novo glioblastoma, between the ages of 18 and 70 years, and with Karnofsky Performance Scale scores of at least 70, were included in the study. Patients were followed monthly and assessed using MRI every 2 months. After a median follow-up of 15 months, the median time to tumor progression was 12.5 months and median survival was 17.8 months. Due to toxicity (mostly hematological), 7 patients had to prematurely stop temozolomide treatment. Twenty-two patients developed Grade 3 CD4(+) lymphocytopenia. Three patients developed oral-esophageal candidiasis, 2 developed pneumonia, and 1 developed a dorsolumbar zoster. Early intracranial hypertension was observed in 1 patient, and 1 was treated empirically for suspected brain abscess. One patient died of Legionella pneumonia soon after repeat surgery. Overall, this treatment schedule produced promising results in terms of PFS without a marked increase in toxicities as compared with the Stupp regimen. However, the gain in median survival using this schedule was less clear. Only prospective comparative trials will determine whether these preliminary results will translate into a long-term survival advantage with an acceptable toxicity profile.


The structure and bonding of Y, Eu, U, Am and Cm complexes as studied by quantum chemical methods and X-ray crystallography.
Two isomers of Y/Eu(TTA)(3)(OH(2)) complexes and their structures were identified by single crystal X-ray diffraction, and their geometry and bond distances were also determined using quantum chemical (QM) methods. The data from the two methods agree very well, suggesting that QM is appropriate for calculating structures for which no experimental data are available. This method was therefore used to determine the structures of U/Am/Cm(TTA)(3)(OH(2))(2) both in gas phase and in CPCM models of CCl(4), CHCl(3), and H(2)O. In these calculations the metal sites were described using the f-in-core approximation, comparing small- and large-core pseudopotentials (SPP and LPP) with their corresponding segmented basis sets. The difference between the Y/Eu-O bond distances between the LPP and SPP is less than 0.02 A. However, in the actinide complexes the LPP results in larger An-O distances and the difference between the LPP and SPP results decreases from about 0.20 A in the U-complex to 0.05 A in the Am- and 0.04 A in the Cm-complex. The chemical bonding studied by population analysis indicates that there is a significant back bonding in U(TTA)(3)(OH(2))(2) from filled orbitals centered on uranium into empty pi* orbitals on coordinated oxygen; there is some evidence of back-bonding also in the americium complex, but a significantly smaller effect in the europium and curium species. The relative energy of the two isomers indicates they may be present in solution in comparable amounts, suggesting the possibility of exchange between them. The X-ray structures suggest two exchange pathways, a topological "twist" mechanism and a site exchange involving the opening of a TTA chelate ring.


Household environmental tobacco smoke and risks of asthma, wheeze and bronchitic symptoms among children in Taiwan.
Although studies show that maternal smoking during pregnancy increases the risks of respiratory outcomes in childhood, evidence concerning the effects of household environmental tobacco smoke (ETS) exposure remains inconsistent. We conducted a population-based study comprised of 5,019 seventh and eighth-grade children in 14 Taiwanese communities. Questionnaire responses by parents were used to ascertain children's exposure and disease status. Logistic regression models were fitted to estimate the effects of ETS exposures on the prevalence of asthma, wheeze, and bronchitic symptoms. The lifetime prevalence of wheeze was 11.6% and physician-diagnosed asthma was 7.5% in our population. After adjustment for potential confounders, in utero exposure showed the strongest effect on all respiratory outcomes. Current household ETS exposure was significantly associated with increased prevalence of active asthma, ever wheeze, wheeze with nighttime awakening, and bronchitis. Maternal smoking was associated with the increased prevalence of a wide range of wheeze subcategories, serious asthma, and chronic cough, but paternal smoking had no significant effects. Although maternal smoking alone and paternal smoking alone were not independently associated with respiratory outcomes, joint exposure appeared to increase the effects. Furthermore, joint exposure to parental smoking showed a significant effect on early-onset asthma (OR, 2.01; 95% CI, 1.00-4.02), but did not show a significant effect on late-onset asthma (OR, 1.17; 95% CI, 0.36-3.87). We concluded that prenatal and household ETS exposure had significant adverse effects on respiratory health in Taiwanese children.


Systematic review and meta-analysis as a structured platform for teaching principles of experimentation.
Access to knowledge has never been easier in the internet age, and so it is important that students develop skills to discriminate undependable information from reliably investigated research. We have created an exercise that teaches good research practice by exploring the history, ethics, and design of clinical trials. Students apply their understanding of these principles through an assessed systematic review and meta-analysis (SRMA) exercise. Here, a clinically themed hypothesis is tested using a structured literature search in conjunction with an eligibility matrix to map study design, ethics, subject selection, randomization and blinding, methodological standards, study power, and other potential sources of interstudy heterogeneity. Data extracted from selected studies are used to produce a forest plot with an aggregated effect size, confidence range, and measure of interstudy heterogeneity. A funnel plot is then used in conjunction with the eligibility matrix to evaluate study bias tendency, and, in this way, students reflect on the factors that promote disparate conclusion-making among studies with a common research focus. This exercise produced a normally distributed grade-profile across three academic-year cohorts, and comparison of individual exercise grade with year-long aggregated average suggested students who performed less well on conventional assignments engaged successfully with the systematic nature of this assessment. Those opting to use this format for their final-year capstone project also performed above their grade point average from the preceding year. We suggest that SRMA offers a readily applied method for students to quantitatively explore how differences in experimental research practices influence study dependability.


Blood pressure in relation to concentrations of PCB congeners and chlorinated pesticides.
Residents of Anniston, Alabama, live near a Monsanto plant that manufactured polychlorinated biphenyls (PCBs) from 1929 to 1971 and are relatively heavily exposed. The goal of this study was to determine the relationship, if any, between blood pressure and levels of total serum PCBs, several PCB groups with common actions or structure, 35 individual PCB congeners, and nine chlorinated pesticides. Linear regression analysis was used to determine the relationships between blood pressure and serum levels of the various contaminants after adjustment for age, body mass index, sex, race, smoking, and exercise in 394 Anniston residents who were not taking antihypertensive medication. Other than age, total serum PCB concentration was the strongest determinant of blood pressure of the covariates studied. We found the strongest associations for those PCB congeners that had multiple ortho chlorines. We found the associations over the full range of blood pressure as well as in those subjects whose blood pressure was in the normal range. The chlorinated pesticides showed no consistent relationship to blood pressure. In this cross-sectional study, serum concentrations of PCBs, especially those congeners with multiple ortho chlorines, were strongly associated with both systolic and diastolic blood pressure.


Extensive lineage-specific gene duplication and evolution of the spiggin multi-gene family in stickleback.
The threespine stickleback (Gasterosteus aculeatus) has a characteristic reproductive mode; mature males build nests using a secreted glue-like protein called spiggin. Although recent studies reported multiple occurrences of genes that encode this glue-like protein spiggin in threespine and ninespine sticklebacks, it is still unclear how many genes compose the spiggin multi-gene family. Genome sequence analysis of threespine stickleback showed that there are at least five spiggin genes and two pseudogenes, whereas a single spiggin homolog occurs in the genomes of other fishes. Comparative genome sequence analysis demonstrated that Muc19, a single-copy mucous gene in human and mouse, is an ortholog of spiggin. Phylogenetic and molecular evolutionary analyses of these sequences suggested that an ancestral spiggin gene originated from a member of the mucin gene family as a single gene in the common ancestor of teleosts, and gene duplications of spiggin have occurred in the stickleback lineage. There was inter-population variation in the copy number of spiggin genes and positive selection on some codons, indicating that additional gene duplication/deletion events and adaptive evolution at some amino acid sites may have occurred in each stickleback population. A number of spiggin genes exist in the threespine stickleback genome. Our results provide insight into the origin and dynamic evolutionary process of the spiggin multi-gene family in the threespine stickleback lineage. The dramatic evolution of genes for mucous substrates may have contributed to the generation of distinct characteristics such as "bio-glue" in vertebrates.


Motor Recovery After Stroke: From a Vespa Scooter Ride Over the Roman Sampietrini to Focal Muscle Vibration (fMV) Treatment. A 99mTc-HMPAO SPECT and Neurophysiological Case Study.
Focal repetitive muscle vibration (fMV) is a safe and well-tolerated non-invasive brain and peripheral stimulation (NIBS) technique, easy to perform at the bedside, and able to promote the post-stroke motor recovery through conditioning the stroke-related dysfunctional structures and pathways. Here we describe the concurrent cortical and spinal plasticity induced by fMV in a chronic stroke survivor, as assessed with 99mTc-HMPAO SPECT, peripheral nerve stimulation, and gait analysis. A 72-years-old patient was referred to our stroke clinic for a right leg hemiparesis and spasticity resulting from a previous (4 years before) hemorrhagic stroke. He reported a subjective improvement of his right leg's spasticity and dysesthesia that occurred after a30-min ride on a Vespa scooter as a passenger over the Roman Sampietrini (i.e., cubic-shaped cobblestones). Taking into account both the patient's anecdote and the current guidelines that recommend fMV for the treatment of post-stroke spasticity, we then decided to start fMV treatment. 12 fMV sessions (frequency 100 Hz; amplitude range 0.2-0.5 mm, three 10-min daily sessions per week for 4 consecutive weeks) were applied over the quadriceps femoris, triceps surae, and hamstring muscles through a specific commercial device (Cro®System, NEMOCOsrl). A standardized clinical and instrumental evaluation was performed before (T0) the first fMV session and after (T1) the last one. After fMV treatment, we observed a clinically relevant motor and functional improvement, as assessed by comparing the post-treatment changes in the score of the Fugl-Meyer assessment, the Motricity Index score, the gait analysis, and the Ashworth modified scale, with the respective minimal detectable change at the 95% confidence level (MDC95). Data from SPECT and peripheral nerve stimulation supported the evidence of a concurrent brain and spinal plasticity promoted by fMV treatment trough activity-dependent changes in cortical perfusion and motoneuron excitability, respectively. In conclusion, the substrate of post-stroke motor recovery induced by fMV involves a concurrently acting multisite plasticity (i.e., cortical and spinal plasticity). In our patient, operant conditioning of both cortical perfusion and motoneuron excitability throughout a month of fMV treatment was related to a clinically relevant improvement in his strength, step symmetry (with reduced limping), and spasticity.


Accuracy of real-time PCR, Gram stain and culture for Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae meningitis diagnosis.
Although cerebrospinal fluid (CSF) culture is the diagnostic reference standard for bacterial meningitis, its sensitivity is limited, particularly when antibiotics were previously administered. CSF Gram staining and real-time PCR are theoretically less affected by antibiotics; however, it is difficult to evaluate these tests with an imperfect reference standard. CSF from patients with suspected meningitis from Salvador, Brazil were tested with culture, Gram stain, and real-time PCR using S. pneumoniae, N. meningitidis, and H. influenzae specific primers and probes. An antibiotic detection disk bioassay was used to test for the presence of antibiotic activity in CSF. The diagnostic accuracy of tests were evaluated using multiple methods, including direct evaluation of Gram stain and real-time PCR against CSF culture, evaluation of real-time PCR against a composite reference standard, and latent class analysis modeling to evaluate all three tests simultaneously. Among 451 CSF specimens, 80 (17.7%) had culture isolation of one of the three pathogens (40 S. pneumoniae, 36 N. meningitidis, and 4 H. influenzae), and 113 (25.1%) were real-time PCR positive (51 S. pneumoniae, 57 N. meningitidis, and 5 H. influenzae). Compared to culture, real-time PCR sensitivity and specificity were 95.0% and 90.0%, respectively. In a latent class analysis model, the sensitivity and specificity estimates were: culture, 81.3% and 99.7%; Gram stain, 98.2% and 98.7%; and real-time PCR, 95.7% and 94.3%, respectively. Gram stain and real-time PCR sensitivity did not change significantly when there was antibiotic activity in the CSF. Real-time PCR and Gram stain were highly accurate in diagnosing meningitis caused by S. pneumoniae, N. meningitidis, and H. influenzae, though there were few cases of H. influenzae. Furthermore, real-time PCR and Gram staining were less affected by antibiotic presence and might be useful when antibiotics were previously administered. Gram staining, which is inexpensive and commonly available, should be encouraged in all clinical settings.


A system approach to dispensing errors: a national study on perceptions of the Finnish community pharmacists.
To examine pharmacists' perceptions and opinions on the potential causes of dispensing errors and the ways to prevent them in community pharmacies, and to assess whether pharmacists' perceptions reflect the system approach. A survey instrument was mailed to privately owned Finnish community pharmacies (n = 599) in March 2005. The survey included two open-ended questions to assess the pharmacists' perceptions on potential causes and prevention of dispensing errors. Furthermore, the questionnaire contained 20 structured, Likert-type, statements of dispensing errors and their management. The survey was addressed to the owner or operational manager of the pharmacy. The emphasis in the analysis of the study was on the open-ended questions which were analysed using the content analysis method. All quantitative data was analysed using the SPSS for Windows. The community pharmacists' perceptions and opinions on the potential causes and preventive factors of dispensing errors. A total of 340 responses were entered in the study (response rate 57%). The content analysis revealed that factors related to organization and those related to individual professionals were the most frequently mentioned as the potential causes of dispensing errors (37% and 30% of all potential causes given, respectively; number of respondents n = 326; total number of given items n = 967). The organizational factors (46% of all the preventive factors given), and factors related to individual professionals (41%) were also the most frequently considered as preventive (number of respondents n = 323; total number of given items n = 916). The analysis of the structured statements revealed that discussion about the dispensing errors with pharmacy staff and changes in working routines based on the dispensing error incidents were considered to be the most important factors in error prevention. A heavy workload and the similarity of drug packages were considered as the most important potential causes of the dispensing errors in the structured statements. Finnish community pharmacists still, to some extent, have the person-centred approach to medication safety although signs of the system approach were also evident. Attitudinal changes still have to take place, as well as changes to the practice environment, in order to get the system approach fully implemented in the Finnish community pharmacies.


Nuclear spin dependence of the reaction of H(3)+ with H2. I. Kinetics and modeling.
The chemical reaction H(3)(+) + H(2) → H(2) + H(3)(+) is the simplest bimolecular reaction involving a polyatomic, yet is complex enough that exact quantum mechanical calculations to adequately model its dynamics are still unfeasible. In particular, the branching fractions for the "identity," "proton hop," and "hydrogen exchange" reaction pathways are unknown, and to date, experimental measurements of this process have been limited. In this work, the nuclear-spin-dependent steady-state kinetics of the H(3)(+) + H(2) reaction is examined in detail, and employed to generate models of the ortho:para ratio of H(3)(+) formed in plasmas of varying ortho:para H(2) ratios. One model is based entirely on nuclear spin statistics, and is appropriate for temperatures high enough to populate a large number of H(3)(+) rotational states. Efforts are made to include the influence of three-body collisions in this model by deriving nuclear spin product branching fractions for the H(5)(+) + H(2) reaction. Another model, based on rate coefficients calculated using a microcanonical statistical approach, is appropriate for lower-temperature plasmas in which energetic considerations begin to compete with the nuclear spin branching fractions. These models serve as a theoretical framework for interpreting the results of laboratory studies on the reaction of H(3)(+) with H(2).


A clinic-based, comprehensive care model for studying late effects in long-term survivors of pediatric illnesses.
Long-term survivors of several childhood illnesses are at risk for multiple late effects of their illness or therapy, and children with documented toxic exposures may also experience long-term health consequences. Clinical studies of these effects are difficult to conduct. The Cardiovascular Status in Childhood Cancer Survivors Study is an established study that highlights the ability to perform comprehensive clinical investigations when patients are cared for in a formal, long-term follow-up clinic. This clinic model facilitates long-term retention and recruitment of patients, allowing comprehensive clinical studies of late effects of illness or exposures, in this case, of cardiovascular complications of cancer treatment during childhood. The study is funded through the National Institute of Health Office of Cancer Survivorship. Participants are recruited from the Long-Term Survivors Clinic at the University of Rochester. The clinic provides care for all survivors of childhood cancer in the region. The Long-Term Survivors Clinic provides medical care and psychosocial and educational support to patients and facilitates coordination of care. Patients remain in close contact with clinic staff for extended periods. We recruited a representative sample of this long-term survivor population, with a wide range of ages, diagnoses, and time since diagnosis. Longitudinal collection of detailed clinical data will enable us to conduct cohort studies of late effects as well as case-control studies of toxic exposures. The success of this study shows the advantages of formal programs for continued care of patients with chronic illnesses or treatment or toxic exposures. The Long-Term Survivors Clinic provides an excellent model for clinical care and research that is applicable to multiple pediatric and young adult populations.


Neutrophil-to-lymphocyte Ratio is a Predictive Marker for Invasive Malignancy in Intraductal Papillary Mucinous Neoplasms of the Pancreas.
To evaluate the correlation between neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) values, and the presence of invasive carcinoma in patients with intraductal papillary mucinous neoplasm (IPMN). NLR and (PLR) are inflammatory markers that have been associated with overall survival in patients with invasive malignancies, including pancreatic cancer. We retrospectively reviewed 272 patients who underwent surgical resection for histologically confirmed IPMN from January 1997 to July 2015. NLR and PLR were calculated and coevaluated with additional demographic, clinical, and imaging data for possible correlation with IPMN-associated carcinoma in the form of a predictive nomogram. NLR and PLR were significantly elevated in patients with IPMN-associated invasive carcinoma (P < 0.001). In the multivariate analysis, NLR value higher than 4 (P < 0.001), IPMN cyst of size more than 3 cm (P < 0.001), presence of enhanced solid component (P = 0.014), main pancreatic duct dilatation of more than 5 mm (P < 0.001), and jaundice (P < 0.001) were statistically significant variables. The developed statistical model has a c-index of 0.895. Implementation of the statistically significant variables in a predictive nomogram provided a reliable point system for estimating the presence of IPMN-associated invasive carcinoma. NLR is an independent predictive marker for the presence of IPMN-associated invasive carcinoma. Further prospective studies are needed to assess the predictive ability of NLR and how it can be applied in the clinical setting.


Potential shifts in dominant forest cover in interior Alaska driven by variations in fire severity.
Large fire years in which >1% of the landscape burns are becoming more frequent in the Alaskan (USA) interior, with four large fire years in the past 10 years, and 79 000 km2 (17% of the region) burned since 2000. We modeled fire severity conditions for the entire area burned in large fires during a large fire year (2004) to determine the factors that are most important in estimating severity and to identify areas affected by deep-burning fires. In addition to standard methods of assessing severity using spectral information, we incorporated information regarding topography, spatial pattern of burning, and instantaneous characteristics such as fire weather and fire radiative power. Ensemble techniques using regression trees as a base learner were able to determine fire severity successfully using spectral data in concert with other relevant geospatial data. This method was successful in estimating average conditions, but it underestimated the range of severity. This new approach was used to identify black spruce stands that experienced intermediate- to high-severity fires in 2004 and are therefore susceptible to a shift in regrowth toward deciduous dominance or mixed dominance. Based on the output of the severity model, we estimate that 39% (approximately 4000 km2) of all burned black spruce stands in 2004 had <10 cm of residual organic layer and may be susceptible a postfire shift in plant functional type dominance, as well as permafrost loss. If the fraction of area susceptible to deciduous regeneration is constant for large fire years, the effect of such years in the most recent decade has been to reduce black spruce stands by 4.2% and to increase areas dominated or co-dominated by deciduous forest stands by 20%. Such disturbance-driven modifications have the potential to affect the carbon cycle and climate system at regional to global scales.


Recurrent angina pectoris.
Coronary artery bypass grafting remains a palliative operation for the relief of angina pectoris refractory to drug therapy, and should be performed in those patients unsuitable for coronary angioplasty. A similar approach can be applied to reoperation in patients with recurrent angina bearing in mind the higher operation-related mortality and reduced prospects for satisfactory relief of symptoms in these patients.


Socially transmitted food preferences can be used to study long-term memory in rats.
Immediately after a recently fed rodent demonstrator interacts with a conspecific observer, the observer shows a substantially enhanced preference for whatever food its demonstrator ate. Here we show that (1) influence of a single, 30-min interaction with a demonstrator on an observer's food preference lasts for at least 1 month, and (2) observers interacting on 2 successive days with a demonstrator fed a different diet on each day show significantly enhanced preferences for both diets a month later. Such enduring effects of single, brief interactions between a demonstrator rat and its observer provide an efficient means for studying physiological and behavioral substrates of long-term memory in rodents. Together with the results of previous studies of social influences on food choices of rats, the present results also suggest that rats may use information acquired from conspecifics to identify both toxic and safe foods for many weeks after they have acquired this information.


Exploring the relationship between history of infertility and the experience of menopausal symptoms.
The aim of the study is to examine longitudinal associations of history of infertility with menopausal symptoms in midlife. Six hundred ninety-five midlife women (≥45 y old or reporting ≥12 mo of amenorrhea at the midlife visit) in Project Viva, a prospective cohort enrolled 1999-2002 during pregnancy and followed for 18 years after enrollment ("midlife visit"). Exposure was history of infertility defined as time to pregnancy ≥12 months (≥6 mo if ≥35 y), use of medical treatment to conceive, or infertility consultation or treatment in the 6-month preceding enrollment. The primary outcome was score below or above the median on the Menopause Rating Scale (MRS). Secondary outcomes included individual symptom score on the MRS and self-reported age of menopause. A total of 36.6% had a history of infertility in their lifetime. At the time of MRS completion, the women with prior infertility were older (53.4 [SD, 3.8] vs 51.2 [SD, 3.7] y) than those without infertility and a larger proportion had reached menopause (62% vs 40%). Women with prior infertility were more likely to score above the median on the MRS (Adjusted Odds Ratio [aOR], 1.45; 95% confidence interval [CI], 1.04-2.01) and had higher odds for reporting any depressive mood (aOR, 1.56; 95% CI, 1.12-2.16) and irritability (aOR, 1.57; 95% CI, 1.13-2.19). There was a trend toward greater severity of sleep problems among women with prior infertility. There was no association of prior infertility with report of other menopausal symptoms or age of menopause. Our findings suggest that women with prior infertility are more likely to have an MRS score above the median and experience depressive mood, irritability, and sleep problems during midlife than women without infertility. These findings have implications for mental health screening among midlife women.


An intelligent mobile vehicle navigator based on fuzzy logic and reinforcement learning.
In this paper, an alternative training approach to the EEM-based training method is presented and a fuzzy reactive navigation architecture is described. The new training method is 270 times faster in learning speed; and is only 4% of the learning cost of the EEM method. It also has very reliable convergence of learning; very high number of learned rules (98.8%); and high adaptability. Using the rule base learned from the new method, the proposed fuzzy reactive navigator fuses the obstacle avoidance behaviour and goal seeking behaviour to determine its control actions, where adaptability is achieved with the aid of an environment evaluator. A comparison of this navigator using the rule bases obtained from the new training method and the EEM method, shows that the new navigator guarantees a solution and its solution is more acceptable.


Current practice in neuropsychological outcome reporting after aneurysmal subarachnoid haemorrhage.
Neuropsychological deficits (NPD) are common in patients with aneurysmal subarachnoid haemorrhage (aSAH). NPD are one of the major limiting factors for patients with an otherwise acceptable prognosis for sustained quality of life. There are only a few studies reporting outcome after aSAH, which used a standardized neuropsychological test battery as a primary or secondary outcome measure. Aim of this study was to determine the current practice of reporting NPD following aSAH in clinical studies. A MEDLINE analysis was performed using the search term "subarachnoid haemorrhage outcome". The latest 1,000 articles were screened. We recorded study design, number of patients, and the presence of neuropsychological outcome report. Additionally, the time of testing after aSAH, the neuropsychological tests administered, as well as the percentage of patients with NPD were analyzed. A total of 324 publications between 2009 and 2012 were selected for further review. Of those, 21 studies (6.5%) reported neuropsychological outcome, in 2,001 of 346,666 patients (0.6%). The assessment of NPD differed broadly using both subjective and objective cognitive evaluation, and a large variety of tests were used. Neuropsychological outcome is underreported, and there is great variety in assessment in currently published clinical articles on aSAH. Prospective randomized trials treating aSAH may benefit from implementing more comprehensive and standardized neuropsychological outcome measures. This approach might identify otherwise unnoticed treatment effects in future interventional studies of aSAH patients.


Hormonal and clinical effects of GnRH agonist alone, or in combination with a combined oral contraceptive or flutamide in women with severe hirsutism.
The objective of this prospective randomized study was to evaluate and compare the hormonal and clinical effects of long-acting gonadotropin-releasing hormone (GnRH) agonist and a combination of GnRH agonist with combined oral contraceptive (COC) or flutamide in women with polycystic ovary syndrome (PCOS). Thirty-five hirsute women with PCOS, ranging in age from 19-27 years, were randomly divided into three groups: group A treated with GnRH agonist (n = 12), group B (n = 12) treated with GnRH agonist plus COC and group C (n = 11) treated with GnRH agonist plus flutamide for 6 months. Before, at the end and 6 months after the end of treatment, blood samples were drawn from all women (in early follicular phase in those with menstrual cycles) to measure ovarian and adrenal androgens, gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH), estradiol and estrone plasma levels. The results showed that all three protocols had good therapeutic efficacy. A significant reduction in hirsutism was observed in all patients after 6 months of therapy, the Ferriman-Gallwey scores dropping to 9 +/- 3 in group A, 10 +/- 4 in group B and 11 +/- 5 in group C. Six months after the end of therapy, the hirsutism score continued to be significantly reduced in all groups. After 6 months of therapy, a reduction in plasma levels of LH, FSH, estrone, estradiol, testosterone, free testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS) was observed in all groups although this was more pronounced in group B and group C. These therapies may be the basis of future treatments that quickly reduce hirsutism and remove its causes by reducing the secretion of ovarian and adrenal androgens and by blocking androgen receptors.


Administration of dexamethasone induces proteinuria of glomerular origin in mice.
The administration of glucocorticoids has been reported to exacerbate proteinuria in a few patients with glomerulonephritis. This effect has not been well recognized, and the pathogenetic mechanism responsible for this phenomenon remains to be clarified. In this study, we observed that a high daily oral dose (0.5 mg/kg body weight) of dexamethasone was capable of inducing overt proteinuria in mice, beginning on day 5 and persisting for a 19-day duration. One fourth of mice also intermittently presented with slight hematuria beginning on day 12. Renal lesions in the dexamethasone-treated mice, which were killed on day 23, were characterized by mild mesangial expansion, segmental or global hyalinosis/sclerosis in deep cortical glomeruli, and focal tubular changes. No glomerular inflammatory cell infiltration or proliferative lesion was noted in any of the mice. Ultrastructural features of glomeruli included mesangial widening characterized by either an increase of mesangial matrix, dilated mesangial channels filled with slightly electron-dense material or mesangial lysis-like appearance showing intracytoplasmic microcysts filled with electron-lucent material, and evidence to support injury of endothelial cells, erythrocytes, and podocytes. An immunofluorescence study revealed enhanced glomerular deposition of IgG, IgA, IgM, and fibrinogen (P < 0.001, compared with normal control mice), but no glomerular C3 deposition was identified in any of the dexamethasone-treated mice. Charge analysis showed no impairment in anionic property of glomerular tufts in the dexamethasone-treated mice. In addition, the dexamethasone-induced proteinuria was greatly attenuated by treatment with a low molecular weight heparin, although it was not reduced by an angiotensin-converting enzyme inhibitor. Data from these experiments suggest that a large dose of glucocorticoids is potentially nephrotoxic. Alteration of a size-dependent permeability may predominantly contribute to the dexamethasone-induced proteinuria. However, the effect of glomerular hyperfiltration may be only partially involved in the pathogenesis of this dexamethasone-induced glomerulopathy in mice.


The pathology of experimental visceral leishmaniasis in resistant and susceptible lines of inbred mice.
1. The main pathological features of experimental visceral leishmaniasis were characterized in resistant and susceptible inbred mouse strains. 2. Disseminated granulomas containing parasitized macrophages were found especially in the liver and spleen of two inbred mouse strains, i.e. the resistant DBA/2 and the susceptible C57BL/10 strains, which had been inoculated with Leishmania donovani chagasi amastigotes. 3. The lesions tended to remain granulomatous in nature even during the early acute phase of the more susceptible mouse strain (C57BL/10), and later evolved to a decrease in number of parasites and granulomas and in granuloma diameter. However, no healing occurred up to the end of the observation period of 70 weeks for the C57BL/10 strain. 4. Visceral leishmaniasis in the mouse model does not resemble the classical human Kala-azar, but seems to be more related to oligosymptomatic forms seen in humans living in endemic areas.


Repletion of sarcoplasmic reticulum Ca after ryanodine in rat ventricular myocytes.
The ryanodine (R)-induced loss of sarcoplasmic reticulum (SR) Ca2+ and the abilities of the SR to accumulate Ca2+ and participate in contractile activation after R were studied in rat ventricular myocytes. Indo 1 fluorescence (IF) indexed cytosolic Ca2+, and caffeine assayed SR Ca2+. Before R, there was a negative staircase, and the SR accumulated Ca2+ at rest. During stimulation (0.5 Hz), R decreased IF and contraction, converting the negative staircase to positive. When R was pulsed onto resting cells, IF increased and cells shortened, subsequently behaving as if stimulated in R. After R, there was no caffeine-releasable Ca2+ at rest, and little accumulated during 0.5-Hz stimulation. At high rates, caffeine-releasable Ca2+ and diastolic IF increased. In isoproterenol and R, IF transients and contractions recovered at 0.5 Hz with a marked positive staircase and little diastolic IF increase. Within 10 beats, SR Ca2+ accumulated to pre-R levels. R eliminated the positive inotropic effect of paired-pulse stimulation, but isoproterenol temporarily restored it. Twitch contractions in thapsigargin, an SR Ca2+ pump blocker, and isoproterenol were slow compared with control or R + isoproterenol. R leaks SR Ca2+ into the cytosol. SR Ca2+ can be repleted in R by high-rate stimulation or by low-rate stimulation with a beta-adrenergic agonist. SR Ca2+ release in R can be temporarily restored if Ca2+ influx and SR Ca2+ pumping are increased enough to overcome the SR Ca2+ leak.


Building community resilience in a context of climate change: The role of social capital.
Social capital is considered important for resilience across social levels, including communities, yet insights are scattered across disciplines. This meta-synthesis of 187 studies examines conceptual and empirical understandings of how social capital relates to resilience, identifying implications for community resilience and climate change practice. Different conceptualisations are highlighted, yet also limited focus on underlying dimensions of social capital and proactive types of resilience for engaging with the complex climate change challenge. Empirical insights show that structural and socio-cultural aspects of social capital, multiple other factors and formal actors are all important for shaping the role of social capital for guiding resilience outcomes. Thus, finding ways to work with these different elements is important. Greater attention on how and why outcomes emerge, interactions between factors, approaches of formal actors and different socio-cultural dimensions will advance understandings about how to nurture social capital for resilience in the context of climate change.


[New non-peptide inhibitors of furin].
Furin, a human subtilisin-related proprotein convertase, is the most important pharmaceutical target because it plays a vital role in development of numerous disease processes. To identify a new class of small non-peptide inhibitors of furin we performed a study of several flavonoids and some natural products. Glycosylated flavonoids: rutin, naringin, baikalin and methylhesperidin were shown to inhibit furin at pH 7.2 reversibly and competitively with Ki- 80-200 microM. The Ki values were derived from Dixon and/or Eadie-Hofstee plots using fluorogenic substrate Boc-Arg-Val-Arg-Arg-AMC. Although studied flavonoids display only a temperate furin inhibition, they may serve as a great potential for the future development of more potent non-peptide inhibitors against furin.


[An experience with the rehabilitation of breast cancer patients after radical treatment].
Breast cancer out-patients rehabilitation may be similarly effective for all tumor localizations provided the peculiarities of primary treatment are considered. Its application opens up new vistas since it ensures an improvement and stabilization of mental and emotional state and reduces anxiety in cancer patients. A course of rehabilitation is followed by the change for better functional indexes and stimulation of interest in taking up an occupation.


Construction of a wireless communication contact closure system for liquid chromatography with multiple parallel mass spectrometers and other detectors.
A contact closure system was constructed that uses two contact closure sender boards that communicate wirelessly to four contact closure receiver boards to distribute start signals from two or three liquid chromatographs to 14 instruments, pumps, detectors, or other components. Default high, closed low, TTL logic (5-volt) start signals from two autosamplers are converted to simple contacts by powered relay boards that are then connected to two 16-channel wireless contact closure sender boards. The contact closure signals from the two sender boards are transmitted wirelessly to two pairs of eight-channel receiver boards (total of 32 contact signals) that distribute the start signal to 14 switches that allow selection of which start signal is sent to which instrument, pump, or detector. The contact closure system is used for quadruple parallel mass spectrometry experiments in which four mass spectrometers, using three different atmospheric pressure ionization modes, plus a UV detector, an evaporative light-scattering detector, a corona charged aerosol detector, and two syringe pumps supplying electrolyte, are all synchronized to start simultaneously. A wide variety of liquid chromatography-mass spectrometry experiments using multiple liquid chromatographs and mass spectrometers simultaneously, LCx/MSy, including column-switching experiments, can be reconfigured simply by toggling switches.


History dependence of rate covariation between neurons during persistent activity in an oculomotor integrator.
Persistent firing in response to a brief stimulus is a neural correlate of short-term memory in a variety of systems. In the oculomotor neural integrator, persistent firing that encodes eye position is maintained in response to transient saccadic eye-velocity commands. To a first approximation, firing rates in the integrator vary linearly with eye position. Thus, viewed across many cells, the pattern of persistent firing in the integrator may be constrained to a unique line of stable states. Here this idea was tested by examining the relationship between firing rates of simultaneously recorded neurons. Paired recordings were obtained in awake goldfish from neurons in hindbrain area I, an essential part of the horizontal eye-position integrator. During spontaneous eye movements consisting of sequential fixations at different horizontal positions, the pair relationship between the majority of cells on the same side of the integrator was not unique: for a given rate of one cell, the rate of the paired cell assumed different values that depended systematically on the preceding saccade history. This finding suggests that the set of persistent firing states that encode eye position is not constrained to a unique line, and that models with stable states restricted to a such a line need to be modified accordingly.


The Caring Efficacy Scale: nurses' self-reports of caring in practice settings.
The Caring Efficacy Scale (CES) assesses belief in one's ability to express a caring orientation and to develop caring relationships with clients or patients. This article describes the development of this Likert-type self-report scale to assess nurses' caring efficacy. It also discusses a preliminary reliability and validity study assessing the caring efficacy of novice and experienced nurses from three nursing programs: baccalaureate, nursing doctorate, and master's. The CES was found to have high internal consistency, and it possessed significant positive relationships with a measure of clinical competence.


Stenosing peroneal tenovaginitis. Case reports.
Stenosing tenovaginitis is a condition in which a narrowing of the synovial tendon sheath occurs. Usually there are no macroscopic or microscopic changes in the tendon or in the synovium. The sheath is usually macroscopically thickened but microscopically normal. Three cases of stenosing peroneal tenovaginitis, 1 bilateral, are presented. In 2 of the patients tenography was used to confirm the diagnosis. The structure of the peroneal tendon sheaths is reviewed, and the successful outcome of tenolysis is described.


A 50,000-year record of climate oscillations from Florida and its temporal correlation with the heinrich events.
Oscillations of Pinus (pine) pollen in a 50,000-year sequence from Lake Tulane, Florida, indicate that there were major vegetation shifts during the last glacial cycle. Episodes of abundant Pinus populations indicate a climate that was more wet than intervening phases dominated by Quercus (oak) and Ambrosia-type (ragweed and marsh-elder). The Pinus episodes seem to be temporally correlated with the North Atlantic Heinrich events, which were massive, periodic advances of ice streams from the eastern margin of the Laurentide Ice Sheet. Possible links between the Tulane Pinus and Heinrich events include hemispheric cooling, the influences of Mississippi meltwater on sea-surface temperatures in the Gulf of Mexico, and the effects of North Atlantic thermohaline circulation on currents in the Gulf.


Low Platelet Counts at Diagnosis Predict Better Survival for Patients with Intermediate-Risk Acute Myeloid Leukemia.
Aggressive growth of primitive and immature cells in the bone marrow results in reductions in megakaryocyte and platelet (PLT) counts, leading to thrombocytopenia in acute myeloid leukemia (AML). However, not all AML patients show thrombocytopenia at the time of diagnosis, and the association of PLT count with patient survival is largely unknown. A retrospective study was performed to determine PLT counts at diagnosis in the peripheral blood in 291 newly diagnosed AML patients and assess the association of PLT counts with the overall survival (OS) and disease-free survival (DFS) of these patients. Low PLT counts (≤40 × 109/L) were associated with better outcomes for the whole cohort (5-year OS, 55.1 ± 3.8 vs. 35.3 ± 3.5%, p < 0.001; 5-year DFS, 49.1 ± 3.8 vs. 25.7 ± 4.0%, p < 0.001) and intermediate-risk patients (5-year OS, 64.5 ± 5.4 vs. 41.0 ± 4.8%, p < 0.001; 5-year DFS, 60.8 ± 5.6 vs. 28.6 ± 5.6%, p < 0.001). Moreover, low PLT counts were related to deeper molecular remission. Low PLT counts correlated with better survival of intermediate-risk AML patients treated with chemotherapy only. Allogeneic hematopoietic stem cell transplantation attenuated the negative impact of high PLT counts on the survival of intermediate-risk patients. Furthermore, univariate and multivariate analyses demonstrated that PLT count at diagnosis was an independent prognostic factor for intermediate-risk AML. PLT count at diagnosis predicts survival for patients with intermediate-risk AML.


Structure of catabolite gene activator protein at 2.9-A resolution. Incorporation of amino acid sequence and interactions with cyclic AMP.
The amino acid sequence of the Escherichia coli catabolite gene activator protein has been fit into a 2.9-A resolution electron density map. Each subunit of the dimer consists of two structurally distinct domains. The larger NH2-terminal domain is seen to bind cyclic AMP and forms all of the contacts between the subunits. The cyclic AMP is completely buried between the interior of the "beta roll" structure of the large domain and a long alpha helix; it makes important hydrogen-bonding interactions with residues from both subunits. The guanidinium group of a buried Arg makes an internal salt link with the phosphate of cyclic AMP. The 6-amino group of adenine interacts simultaneously with both subunits. This interaction with both subunits and the fact that cyclic GMP and cyclic IMP do not activate catabolite gene activator protein suggest that the binding of cyclic AMP may alter the relative orientation of the two subunits, which in turn would change the structure of a DNA binding site that is presumed to span the two smaller domains. The distribution and nature of side chains in the small domain do not rule out the possibility that catabolite gene activator protein binds to left-handed B-DNA.


Identification and characterization of new protein chemoattractants in the frog skin secretome.
The vomeronasal organ is a chemosensory organ present in most vertebrates and involved in chemical communication. In the last decade, the deciphering of the signal transduction process of this organ has progressed. However, less is known about the vomeronasal organ ligands and their structure-function relationships. Snakes possess a highly developed vomeronasal system that is used in various behaviors such as mating, predator detection, or prey selection, making this group a suitable model for study of the vomeronasal chemoreception. In this work, we used a proteomics approach to identify and characterize proteins from frog cutaneous mucus proteome involved in prey recognition by snakes of the genus Thamnophis. Herein we report the purification and characterization of two proteins isolated from the frog skin secretome that elicit the vomeronasal organ-mediated predatory behavior of Thamnophis marcianus. These proteins are members of the parvalbumin family, which are calcium-binding proteins generally associated to muscular and nervous tissues. This is the first report that demonstrates parvalbumins are not strictly restricted to intracellular compartments and can also be isolated from exocrine secretions. Purified parvalbumins from frog muscle and mucus revealed identical chemoattractive properties for T. marcianus. Snake bioassay revealed the Ca(2+)/Mg(2+) dependence of the bioactivity of parvalbumins. So parvalbumins appear to be new candidate ligands of the vomeronasal organ.


Clinical characteristics of patients with fibromyalgia.
Fibromyalgia, also known as fibrositis and muscle rheumatism, is a common, noninflammatory, painful musculoskeletal disorder. It is common between the ages of 30 and 60 years and has a female to male ratio of 5 to 1. Essential symptoms of fibrositis are pain, fatigue, disturbed sleep, morning stiffness and local tenderness. Subjective swelling, paresthesia and numbness sometimes occur. Multiple host and environmental factors seem to contribute to the onset and course of fibromyalgia. Modest improvement follows treatment by antidepressive agents, physical measures and reduction in stress. In this study 60 patients with fibromyalgia were investigated and the clinical characteristics of these patients are described and compared with those in other studies.


Effects of maternal, gestational, and perinatal variables on neonatal line width observed in a modern UK birth cohort.
The objective of this study was to explore potential relationships between neonatal line (NNL) width and early life history variables such as maternal health, gestation, the birth process, and perinatal health. Histological thin sections of deciduous canines were studied from 71 children from the Avon Longitudinal Study of Parents and Children (ALSPAC). The width of the NNL was measured in three locations on the tooth crown using spatial mapping techniques (ArcGIS) from digital images from an Olympus VS-120 microscope. Life history variables were collected prospectively through a combination of clinical observations and questionnaires. Infants born late term or post term had narrower neonatal lines than those born prematurely or at full term. Infants born in Autumn (September to November) had narrower NNLs than those born at other times of year. NNLs in infants born to mothers with hypertension were wider than those without. Infants resuscitated at birth or born to obese mothers had narrower NNLs than those that were not. There was no association between NNL width and either the type or duration of delivery. The NNL in enamel is an irregular accentuated line, but the factors underlying its formation and width remain unclear. In contrast to some previous studies, we found no association between wider NNLs and long or difficult births. Instead, we found that the width of the neonatal line NNL varied in relation to parameters that reflected the prenatal environment and length of gestation.


Serological Responses to Toxoplasma gondii and Matrix Antigen 1 Predict the Risk of Subsequent Toxoplasmic Encephalitis in People Living With Human Immunodeficiency Virus (HIV).
Clinically useful predictors for fatal toxoplasmosis are lacking. We investigated the value of serological assays for antibodies to whole Toxoplasma antigens and to peptide antigens of the Toxoplasma cyst matrix antigen 1 (MAG1), for predicting incident toxoplasmic encephalitis (TE) in people living with human immunodeficiency virus (HIV; PLWH). We performed a nested case control study, conducted within the Multicenter AIDS Cohort Study (MACS), using serum samples obtained 2 years prior to diagnosis of TE from 28 cases, and 37 HIV disease-matched Toxoplasma seropositive controls at matched time-points. Sera were tested for Toxoplasma antibodies using a commercial assay and for antibodies to MAG1_4.2 and MAG1_5.2 peptides in enzyme-linked immunosorbent assay (ELISA). Two years prior to clinical diagnosis, 68% of TE cases were MAG1_4.2 seropositive compared with 16% of controls (odds ratio [OR] 25.0, 95% confidence interval [CI] 3.14-199.18). Corresponding results for MAG1_5.2 seropositivity were 36% and 14% (OR 3.6, 95% CI .95-13.42). Higher levels of antibody to MAG1_4.2 (OR 18.5 per doubling of the optical density [OD] value, 95% CI 1.41-242) and to Toxoplasma (OR 2.91 for each OD unit increase, 95% CI 1.48-5.72) were also associated with the risk of TE. When seropositivity was defined as the presence of MAG1 antibody or relatively high levels of Toxoplasma antibody, the sensitivity was 89% and specificity was 68% for subsequent TE. Antibodies to MAG1 showed predictive value on the occurrence of TE in PLWH, and the predictive performance was further improved by adding the levels of Toxoplasma antibody. These measures could be clinically useful for predicting subsequent diseases in multiple at-risk populations.


Hydrodynamic flow in the cytoplasm of plant cells.
Plant cells show myosin-driven organelle movement, called cytoplasmic streaming. Soluble molecules, such as metabolites do not move with motor proteins but by diffusion. However, is all of this streaming active motor-driven organelle transport? Our recent simulation study (Houtman et al., 2007) shows that active transport of organelles gives rise to a drag in the cytosol, setting up a hydrodynamic flow, which contributes to a fast distribution of proteins and nutrients in plant cells. Here, we show experimentally that actively transported organelles produce hydrodynamic flow that significantly contributes to the movement of the molecules in the cytosol. We have used fluorescence recovery after photobleaching and show that in tobacco Bright Yellow 2 (BY-2) suspension cells constitutively expressing cytoplasmic green fluorescent protein (GFP), free GFP molecules move faster in cells with active transport of organelles than in cells where this transport has been inhibited with the general myosin inhibitor BDM (2,3-butanedione monoxime). Furthermore, we show that the direction of the GFP movement in the cells with active transport is the same as that of the organelle movement and that the speed of the GFP in the cytosol is proportional to the speed of the organelle movement. In large BY-2 cells with fast cytoplasmic streaming, a GFP molecule reaches the other side of the cell approximately in the similar time frame (about 16 s) as in small BY-2 cells that have slow cytoplasmic streaming. With this, we suggest that hydrodynamic flow is important for efficient transport of cytosolic molecules in large cells. Hydrodynamic flow might also contribute to the movement of larger structures than molecules in the cytoplasm. We show that synthetic lipid (DOPG) vesicles and 'stealth' vesicles with PEG phospholipids moved in the cytoplasm.


Cathepsin B Dependent Cleavage Product of Serum Amyloid A1 Identifies Patients with Chemotherapy-Related Cardiotoxicity.
Improvements in long-term cancer survival rates have resulted in an increase in the prevalence of chemotherapy-linked cardiac failure, but treatment-induced cardiac injuries may not be detected until long after therapy. Monitoring cardiac function is recommended; however, cardiovascular injury in cancer patients differs from those with primary cardiac dysfunction, which limits the utility of traditional cardiac biomarkers. Here we examined plasma levels of peptides produced by cathepsin B, which is released during chemotherapy-induced cardiac injury. We applied nanotrap fractionation to enrich plasma peptides from cancer patients treated with or without chemotherapy. Peptides associated with chemotherapy-induced cardiotoxicity, but not other cardiac injury, were identified by mass spectrometry, and their dependence on cathepsin B activity was determined using enzyme inhibition experiments. We found that a peptide (SAA-1525) derived from serum amyloid A1 was significantly increased in cardiotoxicity patients, and its production was inhibited when plasma samples were pretreated with cathepsin B specific inhibitors. Plasma SAA-1525 also correlated with other markers of cardiac injury. Analysis of plasma SAA-1525 levels may hold potential as a rapid and minimally invasive method to monitor subclinical injury, thereby allowing timely intervention to mitigate further cardiac damage and avoid more severe clinical presentation.


Fluoride as a pro-inflammatory factor and inhibitor of ATP bioavailability in differentiated human THP1 monocytic cells.
Chronic exposure of humans to fluorine compounds in the air, water and food may be atherogenic via the activation of oxidative stress and increased ROS production. The most important factor that promotes the formation of ROS seems to be the oxidoreduction of electron carriers in the critical points of the respiratory chain, which depends, among other things, on the cellular demand for ATP. This paper examines the effect of fluorides in concentrations determined in human serum on the intracellular synthesis of ROS, the activity of the respiratory chain enzymes and the synthesis of ATP via oxidative and substrate-level phosphorylation. The incubation of macrophages in fluoride solutions significantly decreased the amount of synthesized cellular ATP and increased formation of ROS and apoptosis in a dose-dependent pattern. The addition of respiratory chain inhibitors resulted in a significant decrease in the synthesized ROS. Sodium fluoride probably promotes oxidative stress in macrophages, which is manifested by a strong increase in ROS synthesis and a decrease in ATP. We suppose that fluoride may destabilize the action of respiratory chain. Our results indicate that the respiratory chain is the main site of ROS synthesis. One cannot exclude the stimulating role of fluorine compounds on the formation of ROS that is independent of the respiratory chain.


Sex-biased gut dopamine signaling in multiple sclerosis.
Multiple sclerosis shows a strong sex bias, with unclear mechanisms. In this issue of Immunity, Peng et al. elucidate a female-biased increase in intestinal dopamine signaling that diminishes protective Lactobacillus and exacerbates inflammation in a mouse model of multiple sclerosis.


Approaches to decrease the prevalence of depression in later life.
Depression is a common and disabling disorder that affects people of all ages and 10% of those older than 65 years. Current strategies to decrease the personal and societal burden of depression in older age rely on the management of people with depression or of those at risk, but benefits have been limited and data remain scant. Existing data suggest that decreasing the onset of a depressive disorder in people at risk is a reasonable way of reducing its prevalence in the community. Older adults with subthreshold symptoms of depression and those who have suffered a stroke have been successfully targeted with various interventions. In addition, the use of collaborative care has improved the immediate and long-term outcome of patients with depression. Finally, the findings of epidemiological studies indicate that a more systematic approach to the management of risk factors might improve the outcome of patients and those at risk, but trial data are still lacking. Current evidence suggests that it is possible to decrease the prevalence of depression in later life, but a more systematic approach to the assessment and management of older adults is necessary.


Is social integration associated with the risk of falling in older community-dwelling women?
Social integration may lead to social support and influence that may in turn protect older community-dwelling adults from falls. We examined incident falls over 3 years across quartiles of social integration scores in 6692 Caucasian women enrolled in the Study of Osteoporotic Fractures (mean age = 77 +/- 5 years). Social integration was assessed using family networks, friendship networks, and interdependence scores. Higher scores correspond to greater integration. Data were analyzed using Poisson regression with generalized estimating equations. Multivariate analyses were used to adjust for other risk factors and potential confounders. Women reported 11863 falls, averaging 0.60 falls per person annually, 95% confidence interval (CI) (0.57, 0.63), or 600 falls per 1000 women. In age-adjusted analysis, the average incidence rate of falls correlated inversely with family networks, interdependence, and composite integration scores (p <.05). In multivariate analysis, increasing family networks were inversely associated with fall risk, p(trend) =.02. Compared to the lowest quartile, the relative risk of falls (95% CI) associated with family network scores in the second, third, and fourth quartiles were 0.90 (0.79-1.03), 0.86 (0.74-1.00), and 0.84 (0.71-0.99), respectively. Strong family networks may protect against the risk of falls in older community-dwelling adults.


Latitudinal comparison of thermotolerance and HSP70 production in F2 larvae of the greenshell mussel (Perna canaliculus).
We report the first measures of thermotolerance (recorded as percentage mortality and induced HSP70 production) for pelagic larvae of three populations of the New Zealand greenshell (green-lipped) mussel Perna canaliculus. Our goal was to determine whether distinct populations of P. canaliculus were more susceptible to predicted climate change than others, and whether such patterns of susceptibility were either genetically controlled (local adaptation of populations) or simply reflect the acclimatory capacity of this species. F2 larvae from three P. canaliculus populations (D'Urville Island, Banks Peninsula and Stewart Island) were subjected to an acute thermal challenge (3 h exposure to a fixed temperature in the range 20-42°C). No latitudinal patterns in either percentage mortality or HSP70 protein production were apparent. For all populations, larval mortality (LT50) was between 32.9 and 33.9°C, with significant amounts of HSP70 induction only occurring in those individuals that experienced temperatures of 40°C or greater. The data presented therefore do not support the hypothesis that genetic adaptation of P. canaliculus to distinct thermal environments will be reflected by a corresponding difference in acute heat tolerance. In fact, the apparently vulnerable veligers show a surprisingly wide thermal safety margin. To develop a comprehensive understanding of the effects of ocean warming upon this species, subsequent studies should consider the impacts of sub-lethal stress upon fitness in addition to chronic thermal challenge and, crucially, the response of sedentary juvenile and adult stages.


[Embolization of indirect carotid-cavernous sinus fistula through the ophthalmic vein].
Indirect or dural carotid cavernous fistulas are abnormal connections between the cavernous sinus and meningeal branches of the external and/or internal carotid arteries. Most of them are idiopathic and occurs spontaneously. Symptoms vary from a tiny episcleral injection to a severe visual loss. Conservative therapy is recomended in cases with few symptoms and no leptomeningeal drainage, as spontaneous resolution is not infrequent. Whenever symptoms worsen, treatment of the fistula should be prescribed. Nowadays, transvenous endovascular treatment consisting of packing the cavernous sinus is the first choice. In most cases, cavernous sinus can be approached through the inferior petrosal sinus. However, sometimes that is not possible, and an approach directly through the superior ophthalmic vein could be necessary. We report a case of a patient with a dural carotid cavernous fistula treated with embolization of the cavernous sinus through the ophthalmic vein.


Effect of exercise on synthesis and degradation of muscle protein.
Several reports have shown that amino acid utilization via oxidation and gluconeogenesis is increased during exercise. The purpose of this study was to investigate whether these changes are accompanied by alterations in protein synthesis and degradation in the muscle of exercising rats. One group of rats was made in swim for 1h and then protein synthesis and protein degradation were measured in a perfused hemicorpus preparation. Protein synthesis was decreased and protein degradation was increased in exercised rats compared with sedentary control rats. Exercise also decreased amino acid incorporation by isolated polyribosomes from muscle. Measurement of several muscle proteinase activities demonstrated that exercise had no effect on alkaline proteinase or Ca2+-activated proteinase. However, the free (unbound) cathepsin D activity was elevated in muscle of exercised rats, whereas the total activity of catepsin D was unchanged. This increase in the proportion of free cathepsin D activity suggests that lysosomal enzymes may be involved in the increased protein degradation that was observed.


Demonstration of a hepatitis C virus-specific antigen predicted from the putative core gene in the circulation of infected hosts.
An ELISA was used to detect a protein derived from the core gene of the hepatitis C virus (HCV) in human plasma. The solid phase antibody in the assay was a murine monoclonal antibody against a synthetic peptide deduced from the putative core gene of HCV (residues 39 to 74). An enzyme-labelled affinity-purified human antibody directed at another region within the HCV core (residues 5 to 23) was the second antibody tracer. The ELISA had a sensitivity capable of detecting a few ng/ml of the HCV core polypeptide expressed in Escherichia coli. Core antigen activity in plasma of infected hosts was detected after treatment of HCV RNA-rich fractions from buoyant density centrifugation with the detergent Tween 80. There was a direct correlation between core antigen ELISA values of a plasma fraction and intensities of polymerase chain reaction signals for HCV RNA. These observations are consistent with the proposal that the N-terminal sequence of the predicted polyprotein of HCV is a nucleocapsid protein, and that improved core antigen assays may correlate with viraemia.


Preventing illicit drug use in adolescents: long-term follow-up data from a randomized control trial of a school population.
National survey data indicate that illicit drug use has steadily increased among American adolescents since 1992. This upward trend underscores the need for identifying effective prevention approaches capable of reducing the use of both licit and illicit drugs. The present study examined long-term follow-up data from a large-scale randomized prevention trial to determine the extent to which participation in a cognitive-behavioral skills-training prevention program led to less illicit drug use than for untreated controls. Data were collected by mail from 447 individuals who were contacted after the end of the 12th grade, 6.5 years after the initial pretest. Results indicated that students who received the prevention program (Life Skills Training) during junior high school reported less use of illicit drugs than controls. These results also support the hypothesis that illicit drug use can be prevented by targeting the use of gateway drugs such as tobacco and alcohol.


[Pandora's box of anatomy].
Physicians in Nazi Germany were among the first to join the Nazi party and the SS, and were considered passionate and active supporters of the regime. Their actions included development and implementation of the racial theory thus legitimizing the development of the Nazi genocide plan, leadership and execution of the sterilization and euthanasia programs as well as atrocious human experimentation. Nazi law allowed the use of humans and their remains in research institutions. One of the physicians whose involvement in the Nazi regime was particularly significant was Eduard Pernkopf. He was the head of the Anatomy Institute at the University of Vienna, and later became the president of the university. Pernkopf was a member of the Nazi party, promoted the idea of "racial hygiene", and in 1938, "purified" the university from all Jews. In Pernkopfs atlas of anatomy, the illustrators expressed their sympathy to Nazism by adding Nazi symbols to their illustrations. In light of the demand stated by the "Yad Vashem" Institute, the sources of the atlas were investigated. The report, which was published in 1998, determined that Pernkopfs Anatomy Institute received almost 1400 corpses from the Gestapo's execution chambers. Copies of Pernkopfs atlas, accidentally exposed at the Rappaport School of Medicine in the Technion, led to dilemmas concerning similar works with a common background. The books initiated a wide debate in Israel and abroad, regarding ethical aspects of using information originated in Nazi crimes. Moreover, these findings are evidence of the evil to which science and medicine can give rise, when they are captured as an unshakable authority.


Panic disorder in primary care: patients' attributions of illness causes and willingness to accept psychiatric treatment.
This study assessed the causes that primary care patients with panic disorder (PD) attribute to their panic symptoms, and their acceptance of various psychiatric treatment options. In a cross-sectional assessment of 306 patients treated at two primary care clinics, 42 met criteria for DSM-IV PD in the past year. The authors classified these 42 PD-positive patients to one of two groups: those receiving both primary and specialty mental health care (PC+MH; n = 19) and those receiving only primary care (PC-only; n = 23). Patients rated the probability of four possible causes of their panic symptoms, and level of acceptability of three psychiatric and two medical treatments for PD. To place primary care patients' ratings into a broader context, a third contrast group of PD-positive patients, recruited from clinical trials of investigational PD pharmacotherapies (n = 31), also rated causes and treatment acceptability. Participants of the three treatment groups attributed psychiatric causes for their panic symptoms in approximately the same proportion (78 percent to 90 percent; p = ns). PC-only participants attributed medical causes for panic symptoms more frequently than PC+MH and PD Clinical Trials participants (48 percent vs. 5 percent and 32 percent; p = .01). Remarkably, the great majority of patients across all groups expressed willingness to see psychiatrists (84 percent to 94 percent) and psychotherapists (95 percent to 100 percent), and to take psychotropic medications (87 percent to 100 percent). In this study most patients attributed a psychiatric cause for panic symptoms and communicated strong acceptance of psychiatric treatment. Thus, we recommend that primary care clinicians more assertively inform their patients of PD diagnoses and recommend psychiatric treatments with less fear about stigmatizing and alienating them.


Rectification of Spin Current in Inversion-Asymmetric Magnets with Linearly Polarized Electromagnetic Waves.
We theoretically propose a method of rectifying spin current with a linearly polarized electromagnetic wave in inversion-asymmetric magnetic insulators. To demonstrate the proposal, we consider quantum spin chains as a simple example; these models are mapped to fermion (spinon) models via Jordan-Wigner transformation. Using a nonlinear response theory, we find that a dc spin current is generated by the linearly polarized waves. The spin current shows rich anisotropic behavior depending on the direction of the electromagnetic wave. This is a manifestation of the rich interplay between spins and the waves; inverse Dzyaloshinskii-Moriya, Zeeman, and magnetostriction couplings lead to different behaviors of the spin current. The resultant spin current is insensitive to the relaxation time of spinons, a property of which potentially benefits a long-distance propagation of the spin current. An estimate of the required electromagnetic wave is given.


Do Molecular Profiles of Primary Versus Metastatic Radioiodine Refractory Differentiated Thyroid Cancer Differ?
Management of metastatic radioiodine refractory differentiated thyroid cancer (DTC) can be a therapeutic challenge. Generally, little is known about the paired molecular profile of the primary tumor and the metastases and whether they harbor the same genetic abnormalities. The present study compared the molecular profile of paired tumor specimens (primary tumor/metastatic sites) from patients with radioiodine refractory DTC in order to gain insight into a possible basis for resistance to radioiodine. Twelve patients with radioiodine refractory metastases were studied; median age at diagnosis of 61 years (range, 25-82). Nine patients had papillary TC (PTC), one had follicular TC (FTC), and two had Hürthle cell TC (HTC). Distant metastases were present in the lungs (n = 10), bones (n = 4), and liver (n = 1). The molecular profiling of paired tumors was performed with a panel of 592 genes for Next Generation Sequencing, RNA-sequencing, and immunohistochemistry. Digital microfluidic PCR was used to investigate TERT promoter mutations. The genetic landscape of all paired sites comprised BRAF, NRAS, HRAS, TP53, ATM, MUTYH, POLE, and NTRK genes, including BRAF and NTRK fusions. BRAF V600E was the most common point mutation in the paired specimens (5/12). TERT promoter mutation C228T was detected in one case. PD-L1 expression at metastatic sites was highly positive (95%) for one patient with HTC. All specimens were stable for microsatellite instability testing, and the tumor mutation burden was low to intermediate. Therefore, the molecular profile of DTC primary and metastatic lesions can show heterogeneity, which may help explain some altered responses to therapeutic intervention.


A Mutation of the Prdm9 Mouse Hybrid Sterility Gene Carried by a Transgene.
PRDM9 is a protein with histone-3-methyltransferase activity, which specifies the sites of meiotic recombination in mammals. Deficiency of the Prdm9 gene in the laboratory mouse results in complete arrest of the meiotic prophase of both sexes. Moreover, the combination of certain PRDM9 alleles from different mouse subspecies causes hybrid sterility, e.g., the male-specific meiotic arrest found in the (PWD/Ph × C57BL/6J)F1 animals. The fertility of all these mice can be rescued using a Prdm9-containing transgene. Here we characterized a transgene made from the clone RP24-346I22 that was expected to encompass the entire Prdm9 gene. Both (PWD/Ph × C57BL/6J)F1 intersubspecific hybrid males and Prdm9-deficient laboratory mice of both sexes carrying this transgene remained sterile, suggesting that Prdm9 inactivation occurred in the Tg(RP24-346I22) transgenics. Indeed, comparative qRT-PCR analysis of testicular RNAs from transgene-positive versus negative animals revealed similar expression levels of Prdm9 mRNAs from the exons encoding the C-terminal part of the protein but elevated expression from the regions coding for the N-terminus of PRDM9, indicating that the transgenic carries a new null Prdm9 allele. Two naturally occurring alternative Prdm9 mRNA isoforms were overexpressed in Tg(RP24-346I22), one formed via splicing to a 3'-terminal exon consisting of short interspersed element B2 and one isoform including an alternative internal exon of 28 base pairs. However, the overexpression of these alternative transcripts was apparently insufficient for Prdm9 function or for increasing the fertility of the hybrid males.


Player and Game Characteristics and Head Impacts in Female Youth Ice Hockey Players.
Despite the growing popularity of ice hockey among female youth and interest in the biomechanics of head impacts in sport, the head impacts sustained by this population have yet to be characterized. To describe the number of, biomechanical characteristics of, and exposure to head impacts of female youth ice hockey players during competition and to investigate the influences of player and game characteristics on head impacts. Cohort study. Twenty-seven female youth ice hockey players (mean age = 12.5 ± 0.52 years) wore instrumented ice hockey helmets during 66 ice hockey games over a 3-year period. Data specific to player, game, and biomechanical head impact characteristics were recorded. A multiple regression analysis identified factors most associated with head impacts of greater frequency and severity. A total of 436 total head impacts were sustained during 6924 minutes of active ice hockey participation (0.9 ± 0.6 impacts per player per game; range, 0-2.1). A higher body mass index (BMI) significantly predicted a higher number of head impacts sustained per game (P = .008). Linear acceleration of head impacts was greater in older players and those who played the forward position, had a greater BMI, and spent more time on the ice (P = .008), whereas greater rotational acceleration was present in older players who had a greater BMI and played the forward position (P = .008). During tournament games, increased ice time predicted increased severity of head impacts (P = .03). This study reveals for the first time that head impacts are occurring in female youth ice hockey players, albeit at a lower rate and severity than in male youth ice hockey players, despite the lack of intentional body checking.


Nutrition and mortality in hemodialysis.
Protein-energy malnutrition is present in a large proportion of maintenance hemodialysis (HD) patients, and it is associated with increased morbidity and mortality. The protein requirements are increased because of the presence of endocrine and metabolic factors related to loss of renal function, the HD procedure, and comorbidity factors, which all stimulate net protein catabolism. The intake protein and energy are frequently reduced because of the underlying disease, psychosocial factors, and uremic anorexia. However, the extent to which underdialysis contributes to anorexia and malnutrition is still not well defined. Malnutrition is generally not recognized as a common direct cause of death as reflected in health statistics, except in the highest age groups. Anthropometric and biochemical signs of malnutrition are associated with increased mortality. A low serum albumin level is a strong predictive risk factor that may reflect not only or mainly protein malnutrition but also the influence of several other morbidity factors (overhydration, infection, chronic disease and others) that may entail an increased risk of death. Low levels of serum creatinine (low muscle mass), serum cholesterol (energy depletion), and BUN and low urea appearance rate (low protein intake) are also correlated to increased mortality. For the prevention and treatment of HD-associated malnutrition, measures should be taken to correct factors that may suppress appetite and increase net protein catabolism (underdialysis, acidosis, low energy intake, comorbid conditions, psychosocial and economic factors). Dietary advice should be given with the aim of ensuring an adequate intake of protein- and energy-giving products. Intradialytic parenteral nutrition may have positive effects on nutritional status when other measures fail. However, the indications for such treatment have not yet been well defined, and the effects on survival, morbidity, and quality of life are not sufficiently well proved. More and better data, generated in prospective, well-controlled studies, are obviously needed before intradialytic parenteral nutrition can be generally recommended as therapy for malnourished HD patients.


Endothelial cells exposed to erythrocytes under shear stress: an in vitro study.
After injury and vascular replacement, endothelial cell recovery is limited and could lead to thrombosis. Seeding small diameter vascular prosthesis with endothelial cells has been proposed to fulfil cell lining and improve surface hemocompatibility. However, detachment of seeded cells occurs following implantation. Previous in vitro studies have looked at the fluid shear stress as a major cause of cell detachment. To our knowledge, the role of erythrocyte collisions has not been investigated. The present in vitro study aims at investigating whether endothelial cell adhesion depends on (i) the presence of erythrocytes in flow and (ii) the latent culture period (1, 24 and 48 h) between seeding and exposure to flow. Endothelial cells were exposed to culture media containing different erythrocyte concentrations using a steady laminar flow of 1350 ml min(-1) in a parallel plate flow chamber. Endothelial cell morphology in dynamic conditions was quantified and compared to that in static conditions. The projected area of cells were mostly found smaller under dynamic than static conditions, particularly at a wall shear stress of 23 dyn cm(-2). Cells from the 1 h latent culture period were oriented parallel to the flow axis and were more elongated than under static conditions. Conversely, endothelial cell shape was slightly modified when either the latent period or the wall shear stress was increased. Disparate orientation was observed on confluent endothelial cells (24-48 h latent period) exposed to shear stress with or without erythrocytes. Increasing fluid viscous forces due to erythrocytes play a critical role on the behaviour of freshly seeded endothelial cells upon exposure to blood flow.


Addressing overtreatment in patients with refractory epilepsy at a tertiary referral centre in Brazil.
Patients with refractory epilepsy often have impaired quality of life (QOL) as a consequence of seizures and adverse effects of antiepileptic drugs. We assessed the impact of adverse effects on QOL and the utility of a structured instrument to help the physician manage adverse effects in patients with refractory epilepsy. Clinical characteristics, drug treatment and adverse effects were evaluated in 102 patients with refractory epilepsy at a single tertiary referral centre. The Adverse Events Profile (AEP) and Quality of Life in Epilepsy-31 (QOLIE-31) questionnaires were completed at baseline and after six months. At baseline, patients with a high burden of adverse effects (AEP scores ≥45) were randomized to an intervention or control group. AEP scores in the intervention group were available to the physician as an instrument to help to reduce adverse effects. Ninety-five patients (93.1%) were on polytherapy. Sixty-six completed the questionnaires and, of these, 43 (65.1%) had a high AE burden and were randomized to the intervention and control group. QOLIE-31 scores were inversely correlated with AEP scores at both visits. Among randomized patients, AEP scores tended to decrease between the baseline and the final visit without significant differences between groups (intervention group: 54.1 ± 6.1 vs 51.1 ± 9.1; control group: 55.8 ± 5.8 vs 50.5 ± 12.2). QOLI-31 scores did not change substantially between visits (intervention group: 45.9 ± 17.4 vs 48.4 ± 14; control group: 47.5 ± 15.7 vs 45.2 ± 18.9). A significant proportion of patients had a high toxicity burden which had an impact on their QOL. Reduction of overtreatment is a difficult challenge which cannot be addressed solely by providing a structured assessment of adverse effects, but requires a more comprehensive approach aimed at optimizing the many components of the management strategy.


A tightly regulated system for overproduction of bacteriophage T4 lysozyme in Escherichia coli.
Bacteriophage T4 lysozyme has been purified using the Ni-chelate affinity chromatography technique from overexpressing Escherichia coli cells by fusion to an N-terminal 6x His tail. Regulation of the lysozyme gene expression has been found to be critical during growth phase of the bacteria by comparing different plasmid constructions. Whereas a tac-promoter fusion construct alone did not lead to efficient production of T4 lysozyme because of early cell lysis, an improved repressor sequence and co-overproduction of the tac repressor resulted in high-level synthesis of the foreign protein after IPTG induction. Purification of the fusion protein from autolyzed crude cell extracts is possible in a simple one-step procedure.


[Natural course of Ebstein's anomaly].
The natural course of Ebstein's anomaly of the tricuspid valve was studied in 42 conservative patients, their age ranging from 1 day to 38 years at 1st examination (12.3 +/- 1.5 years). Twenty-seven of 42 patients reported for a follow-up check after 3 to 21 years, while the remaining 15 had died as a natural outcome of the defect, heart failure and rhythm disorders being the most common causes of death. The 27 survivors had reached the age of 7-54 years (33.8 +/- 4.2 years), all of them showing a deterioration of the condition and progressing cardiomegaly.


Carbon consequences and agricultural implications of growing biofuel crops on marginal agricultural lands in China.
Using marginal agricultural lands to grow energy crops for biofuel feedstocks is a promising option to meet the biofuel needs in populous China without causing further food shortages or environmental problems. Here we quantify the effects of growing switchgrass and Miscanthus on Chinese marginal agricultural lands on biomass production and carbon emissions with a global-scale biogeochemical model. We find that the national net primary production (NPP) of these two biofuel crops are 622 and 1546 g C m(-2) yr(-1), respectively, whereas the NPP of food crops is about 600 g C m(-2) yr(-1) in China. The net carbon sink over the 47 Mha of marginal agricultural lands across China is 2.1 Tg C yr(-1) for switchgrass and 5.0 Tg C yr(-1) for Miscanthus. Soil organic carbon is estimated to be 10 kg C m(-2) in both biofuel ecosystems, which is equal to the soil carbon levels of grasslands in China. In order to reach the goal of 12.5 billion liters of bioethanol in 2020 using crop biomass as biofuel feedstocks, 7.9-8.0 Mha corn grain, 4.3-6.1 Mha switchgrass, or 1.4-2.0 Mha Miscanthus will be needed. Miscanthus has tremendous potential to meet future biofuel needs, and to benefit CO(2) mitigation in China.


Use of spatial phase shifting technique in digital speckle pattern interferometry (DSPI) and digital shearography (DS).
Digital speckle pattern interferometry (DSPI) and digital shearography (DS) are well known optical tools for qualitative as well as quantitative measurements of displacement components and its derivatives of engineering structures subjected either static or dynamic load. Spatial phase shifting (SPS) technique is useful for extracting quantitative displacement data from the system with only two frames. Optical configurations for DSPI and DS with a double aperture mask in front of the imaging lens for spatial phase shifting are proposed in this paper for the measurement of out-of-plane displacement and its first order derivative (slope) respectively. An error compensating four-phase step algorithm is used for quantitative fringe analysis.


Role of the aryl hydrocarbon receptor in carcinogenesis and potential as a drug target.
The aryl hydrocarbon receptor (AHR) is highly expressed in multiple organs and tissues, and there is increasing evidence that the AHR plays an important role in cellular homeostasis and disease. The AHR is expressed in multiple tumor types, in cancer cell lines, and in tumors from animal models, and the function of the AHR has been determined by RNA interference, overexpression, and inhibition studies. With few exceptions, knockdown of the AHR resulted in decreased proliferation and/or invasion and migration of cancer cell lines, and in vivo studies in mice overexpressing the constitutively active AHR exhibited enhanced stomach and liver cancers, suggesting a pro-oncogenic role for the AHR. In contrast, loss of the AHR in transgenic mice that spontaneously develop colonic tumors and in carcinogen-induced liver tumors resulted in increased carcinogenesis, suggesting that the receptor may exhibit antitumorigenic activity prior to tumor formation. AHR ligands also either enhanced or inhibited tumorigenesis, and these effects were highly tumor specific, demonstrating that selective AHR modulators that exhibit agonist or antagonist activities represent an important new class of anticancer agents that can be directed against multiple tumors.


More Than a Tumor Marker…A Potential Role for Alpha-Feto Protein in Inflammatory Bowel Disease.
Human alpha-fetoprotein (hAFP) is a glycoprotein derived from the gut entoderm and expressed sequentially by cells of the yolk sac, fetal liver, and gastrointestinal tract. By adulthood, serum levels of alpha-fetoprotein (AFP) are undetectable in healthy, nonpregnant adults. Despite the clinical utilities of AFP monitoring in pregnancy and malignancy, much remains to be determined regarding its potential physiological functions. We focused on literature related to AFP's immunoregulatory role and its ability to modulate disease activity both in animal models of autoimmune disorders and in human clinical studies. Evidence suggests that AFP plays an important role in immunoregulation by inducing T-cell suppressor activity, downregulating dendritic-like cell antigen expression, and impairing the function of macrophages. Studies evaluating AFP and its effects in rodent models of autoimmune diseases have shown that AFP is associated with downregulation of inflammation. Observations in studies of pregnant patients with immune-mediated inflammatory diseases have also described potential correlations between AFP expression and disease activity during different stages of pregnancy and postpartum. We propose further prospective evaluations of AFP expression during pregnancy in inflammatory bowel disease patients to further correlate with disease activity and consider the potential of AFP as a novel therapeutic agent.


Does heparin pretreatment affect the haemostatic system during and after cardiopulmonary bypass?
In this clinical pilot study, the influence of heparin pretreatment on the haemostatic system during and after cardiopulmonary bypass (CPB) was investigated. Thirteen patients scheduled for elective coronary artery bypass grafting (CABG) were divided into two groups: heparin pretreated (HP, n = 6) and non-heparin pretreated (NHP, n = 7). Blood samples were taken for measurements of plasma antithrombin-III (AT-III) activity, plasma heparin levels, activated clotting time with (HACT) and without (ACT) heparinase, whole blood platelet function, platelet count, thrombin-antithrombin-III complexes and D-dimer levels. Also, the mediastinal blood loss within the initial 20 h after surgery, and the blood transfusion requirements were monitored. The mean duration of the heparin pretreatment was 55 h (range 24-161 h). There was no significant difference in plasma AT-III activity and platelet count between the groups. Before and after CPB, the platelet responsiveness was better in the NHP group (p < 0.05). The HACT was prolonged in the NHP group during and after CPB compared to baseline values (p < 0.05), whereas, in the HP group, no significant changes were found. Plasma heparin levels and ACT values suggested adequate anticoagulation during CPB. However, the extent of thrombin inhibition and fibrinolysis increased with time on CPB, but did not differ between the two groups. Twenty hours after surgery, the thrombin inhibition showed to be significantly higher in the NHP group. Furthermore, mediastinal blood loss showed a tendency to be lower in the HP group (p = 0.08). However, there was no difference in blood transfusion requirements between the groups. These data suggest that short-term heparin pretreatment affects the perioperative platelet responsiveness and attenuates the consumption of coagulation factors.


The man who feels two hearts: the different pathways of interoception.
Recent advances in neuroscience have provided new insights into the understanding of heart-brain interaction and communication. Cardiac information to the brain relies on two pathways, terminating in the insular cortex (IC) and anterior cingulate cortex (ACC), along with the somatosensory cortex (S1-S2). Interoception relying on these neuroanatomical pathways has been shown to modulate social cognition. We report the case study of C.S., a patient with an 'external heart' (an extracorporeal left-univentricular cardiac assist device, LVAD). The patient was assessed with neural/behavioral measures of cardiac interoception complemented by neuropsychological and social cognition measures. The patient's performance on the interoception task (heartbeat detection) seemed to be guided by signals from the artificial LVAD, which provides a somatosensory beat rather than by his endogenous heart. Cortical activity (HEP, heartbeat-evoked potential) was found decreased in comparison with normal volunteers, particularly during interoceptive states. The patient accurately performed several cognitive tasks, except for interoception-related social cognition domains (empathy, theory of mind and decision making). This evidence suggests an imbalance in the patient's cardiac interoceptive pathways that enhances sensation driven by the artificial pump over that from the cardiac vagal-IC/ACC pathway. A patient with two hearts, one endogenous and one artificial, presents a unique opportunity to explore models of interoception and heart-brain interaction.


Predictors of outcome for patients with substance-use disorders five years after treatment dropout.
Few studies focus on the outcome of patients after they drop out of substance-use disorder (SUD) treatment, and there appear to be no prior studies of the long-term outcomes of these patients. The aim of this study is to determine how well such patients do after dropping out of treatment and to identify predictors of differential outcomes. Patients in 15 residential SUD treatment programs were assessed at treatment entry and at 5-year follow-up on their frequency and severity of substance use, expectancies and beliefs about substance use, and social resources and stressors. Patients who dropped out and stayed out of treatment (n = 193) were compared with those who completed treatment (n = 3,204). Predictors of 5-year SUD problems among dropouts were identified. In general, dropouts and treatment completers did not differ significantly on their levels of SUD problems at 5 years. At baseline, patients who dropped out reported more involvement in 12-step organizations and greater cognitive impairment and more closely identified with the label "drug addict" than "alcoholic." Lower severity of SUD, lower self-efficacy, fewer positive substance- use expectancies, and less stress from social networks predicted fewer SUD problems at 5 years among dropouts. In addition to focusing on substance use, providers should address the adequacy of patients' social support and counter positive substance-use expectancies at the earliest stages of treatment before patients drop out.