Translating basic research knowledge on the biological embedding of early-life stress into novel approaches for the developmental programming of lifelong health.
This review integrates scientific knowledge obtained over the past few decades on the biological mechanisms that contribute to the profound association between exposure to early adversity, including childhood trauma and prenatal stress, and the lifelong elevated risk to develop a broad range of diseases. We further discuss insights into gene-environment interactions moderating the association between early adversity and disease manifestation and we discuss the role of epigenetic and other molecular processes in the biological embedding of early adversity. Based on these findings, we propose potential mechanisms that may contribute to the intergenerational transmission of risk related to early adversity from the mother to the fetus. Finally, we argue that basic research knowledge on the biological embedding of early adversity must now be translated into novel intervention strategies that are mechanism-driven and sensitive to developmental timing. Indeed, to date, there are no diagnostic biomarkers of risk or mechanism-informed interventions that we can offer to victims of early adversity in order to efficiently prevent or reverse adverse health outcomes. Such translational efforts can be expected to have significant impact on both clinical practice and the public health system, and will promote precision medicine in pediatrics and across the lifespan.


Obese patients with castration-resistant prostate cancer may be at a lower risk of all-cause mortality: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database.
To assess whether obesity is associated with progression to metastasis, prostate cancer-specific mortality (PCSM), and all-cause mortality (ACM), in patients with non-metastatic castration-resistant prostate cancer (non-mCRPC). At the population level, obesity is associated with prostate cancer mortality; however, some studies have found that higher body mass index (BMI) is associated with better long-term prostate cancer outcomes amongst men with mCRPC. We identified 1 192 patients with non-mCRPC from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. BMI was calculated from height and weight abstracted from the medical records at the time closest to but prior to CRPC diagnosis and categorised as underweight (<21 kg/m2 ), normal weight (21-24.9 kg/m2 ), overweight (25-29.9 kg/m2 ), and obese (≥30 kg/m2 ). Competing risks regression and Cox models were used to test associations between obesity and progression to metastasis, PCSM, and ACM, accounting for confounders. Overall, 51 (4%) men were underweight, 239 (25%) were normal weight, 464 (39%) were overweight, and 438 (37%) were obese. In adjusted analysis, higher BMI was significantly associated with reduced ACM (hazard ratio [HR] 0.98, P = 0.012) but not PCSM (HR 1.00, P = 0.737) or metastases (HR 0.99, P = 0.225). Likewise, when BMI was treated as a categorical variable in adjusted models, obesity was not associated with PCSM (HR 1.11, P = 0.436) or metastases (HR 1.06, P = 0.647), but was associated with decreased ACM (HR 0.79, P = 0.016) compared to normal weight. No data were available on treatments received after CRPC diagnosis. Amongst patients with non-mCRPC obesity was associated with better overall survival. Although this result mirrors evidence from men with mCRPC, obesity was not associated with prostate cancer outcomes. Larger studies are needed to confirm these findings.


Malpractice premiums in Massachusetts, a high-risk state: 1975 to 2005.
Massachusetts has the fourth-highest median malpractice settlement payments for all states. The American Medical Association (AMA) declares it a crisis state. As a test case, we analyzed its premiums from 1975 to 2005. In 2005 mean premiums were $17,810 for the coverage level and policy type most frequently purchased. Most physicians paid lower inflation-adjusted premiums in 2005 than in 1990. Mean premiums increased in only three specialties comprising 4 percent of physicians: obstetrics, neurology, and orthopedists-spinal surgery. However, because of discounts and surcharges, in 2005 premiums within the three highest-risk specialties varied nearly threefold, and nearly one-third paid less than in 1990.


Micronutrient Fortified Condiments and Noodles to Reduce Anemia in Children and Adults--A Literature Review and Meta-Analysis.
Micronutrient deficiencies impose a considerable burden of disease on many middle and low income countries. Several strategies have been shown to be effective in improving micronutrient deficiencies. However, the impact of fortified condiments as well as fortified noodles is less well documented. We aimed to investigate existing evidence on the impact of micronutrient fortified condiments and noodles on hemoglobin, anemia, and functional outcomes in children and adults (age: 5 to 50 years). We conducted a literature review in electronic databases. In addition, we screened the homepages of relevant organizations and journals. We included randomized controlled trials (RCT). Of 1046 retrieved studies, 14 RCT provided data for the meta-analysis. Micronutrient fortification of condiments and noodles increased hemoglobin concentrations by 0.74 g/dL (95%-confidence intervals (95%-CI): 0.56 to 0.93; 12 studies) and 0.3 g/dL (95%-CI: 0.12 to 0.48; 1 study), respectively. Micronutrient fortification also led to a reduced risk of having anemia (risk ratio 0.59 (95%-CI 0.44 to 0.80)). Ferritin concentrations increased with fortified condiments. Functional outcomes were rarely assessed and showed mixed results. The use of micronutrient fortified condiments can be a strategy to reduce anemia in children and adults due to micronutrient deficiencies. The effect of fortified noodles seems to be smaller.


Photogenotoxicity of fluoroquinolones in Chinese hamster V79 cells: dependency on active topoisomerase II.
The Chinese hamster V79 lung cell in vitro micronucleus assay was adapted to detect and quantify phototoxicity and photogenotoxicity of fluoroquinolones. Using this assay, the quinolones were ranked in terms of decreasing phototoxicity: clinafloxacin >> lomefloxacin, sparfloxacin >> trovafloxacin, nalidixic acid, ofloxacin, ciprofloxacin > enoxacin, norfloxacin. This rank order agrees well with published studies utilizing various other phototoxicity models and establishes this approach as a fast and sensitive way to characterize the phototoxic potential of quinolones. Nearly complete inhibition of phototoxicity was observed if the cells were pretreated for as little as 1 min with 10-20 mM sodium azide prior to the addition of quinolone. An identical azide effect was seen in unirradiated quinolone- and etoposide-treated cells. These findings are consistent with a model in which sodium azide renders DNA topoisomerase II catalytically inactive. In this state, topoisomerase II cannot initiate DNA strand cleavage and the DNA/topoisomerase complex becomes insensitive to quinolones and other topoisomerase II inhibitors. The fact that azide reduces both UV-dependent and UV-independent toxicity and clastogenicity strongly suggests a common mechanism of toxicity dependent on the formation of topoisomerase-induced DNA double-strand breaks.


Detecting impaired language processing in patients with mild cognitive impairment using around-the-ear cEEgrid electrodes.
Mild cognitive impairment (MCI) is the term used to identify those individuals with subjective and objective cognitive decline but with preserved activities of daily living and an absence of dementia. Although MCI can impact functioning in different cognitive domains, most notably episodic memory, relatively little is known about the comprehension of language in MCI. In this study, we used around-the-ear electrodes (cEEGrids) to identify impairments during language comprehension in patients with MCI. In a group of 23 patients with MCI and 23 age-matched controls, language comprehension was tested in a two-word phrase paradigm. We examined the oscillatory changes following word onset as a function of lexico-semantic single-word retrieval (e.g., swrfeq vs. swift) and multiword binding processes (e.g., horse preceded by swift vs. preceded by swrfeq). Electrophysiological signatures (as measured by the cEEGrids) were significantly different between patients with MCI and controls. In controls, lexical retrieval was associated with a rebound in the alpha/beta range, and binding was associated with a post-word alpha/beta suppression. In contrast, both the single-word retrieval and multiword binding signatures were absent in the MCI group. The signatures observed using cEEGrids in controls were comparable with those signatures obtained with a full-cap EEG setup. Importantly, our findings suggest that patients with MCI have impaired electrophysiological signatures for comprehending single words and multiword phrases. Moreover, cEEGrid setups provide a noninvasive and sensitive clinical tool for detecting early impairments in language comprehension in MCI.


The use of sniffer dogs for early detection of cancer: a One Health approach.
This review, which is part of the "Currents in One Health" series, describes and evaluates the current research on the utilization of trained medical scent detection, aka "sniffer" dogs for the detection of diseases, with particular emphasis on neoplasia, both within human and veterinary patients. A recent study by the authors that used sniffer dogs to detect differences in saliva from dogs diagnosed with various neoplastic processes compared with healthy control dogs is described. The concept of One Health is explored by the description of previous studies that have utilized sniffer dogs in the detection of human neoplasia (focusing on lung, prostate, and breast cancer) and veterinary neoplasia and demonstrating that further research in this arena can benefit multiple species. Future avenues of research and utilization of these findings are outlined. The companion Currents in One Health by Ungar et al, JAVMA, January 2024, addresses the use of sniffer dogs to detect human COVID-19 infections.


Interfacing multicellular organisms with polyelectrolyte shells and nanoparticles: a Caenorhabtidis elegans study.
We report the surface modification of microscopic live multicellular nematodes Caenorhabtidis elegans with polyelectrolyte multilayers (pure and doped with 20 nm gold nanoparticles) and the direct magnetic functionalization of nematodes with biocompatible magnetic nanoparticles. Magnetically functionalized "ironoxideclad" nematodes can be effectively separated and moved using an external magnetic field. The surface-functionalized nematodes preserve their viability and reproduction.


Orthotopic liver transplantation for biliary atresia. Evolution of management.
Forty-five patients with biliary atresia were accepted for orthotopic liver transplantation. Nine patients died awaiting transplantation, and 36 underwent transplantation. A portoenterostomy had been performed in 28 of these 36 patients, and its presence did not significantly affect the intraoperative blood loss (5.6 vs 4.1 blood volumes), the need for retransplantation (21% vs 12%), biliary complications (21% vs 12%), postoperative infections (36% vs 25%), or survival (82% vs 63%). These results indicate that early portoenterostomy is appropriate early therapy for biliary atresia; however, prompt referral to a liver transplant center for evaluation at the first sign of cholestasis is needed to attain optimal results for transplantation. Revisions of the portoenterostomy prior to transplantation did not improve the longevity of the procedure but did substantially increase complications and death after orthotopic liver transplantation.


Association between colchicine resistance and vitamin D in familial Mediterranean fever.
Although colchicines are the only effective treatment of familial Mediterranean fever (FMF), resistance to colchicines (CR) which is observed in up to 30% of the patients is still a problem. Clinically, resistance to colchicine is defined as three or more attacks within the last 6 months period while using ≥2 mg/day colchicine. Previous studies have shown decreased vitamin D levels in FMF patients compared with healthy controls. The aim of this study is to evaluate whether vitamin D levels differ between CR and non-CR FMF patients. This study included 64 FMF patients who were being followed in Nephrology Clinic of Samsun Research and Education Hospital for at least 1 year. FMF was diagnosed according to the criteria defined by Livneh et al. Serum 25-hydroxy vitamin D (25-OHD) concentration (ng/mL) was detected in all FMF patients who were not in an acute attack period. From 64 patients 29 were accepted as CR. Mean 25-OHD level was 9.39 ± 1.00 ng/mL in CR patients and 18.48 ± 1.09 ng/mL in colchicine responsive patients (p < 0.001). Plasma vitamin D levels were significantly lower in colchicine resistant patients. Vitamin D deficiency may be a factor in etiopathogenesis of CR. Studies in larger patient samples that particularly evaluate the response to vitamin D replacement in CR FMF patients are needed.


Abnormal sodium efflux in erythrocytes of patients with essential hypertension.
Erythrocyte sodium efflux as well as sodium, potassium, and water content were studied in 12 untreated men with uncomplicated essential hypertension and in 18 normotensive control subjects. In the patients with essential hypertension, the rate constant for total sodium efflux was significantly lower than in the normotensives (5.96.10(-3) +/- 0.45.10(-3) min-1 vs 6.69.10(-3) +/- 0.49.10(-3) min-1; p less than 0.005), which was due to a reduced ouabain-sensitive sodium efflux rate constant. Significant differences in total sodium efflux and ouabain-sensitive sodium efflux, however, could not be demonstrated, since intracellular sodium concentrations, although insignificant, were higher in the patients with essential hypertension (6.11 +/- 0.74 mmole/liter vs 5.97 +/- 0.66 mmole/liter. The rate constants for ouabain-insensitive sodium efflux, for ouabain-insensitive furosemide-sensitive sodium efflux, and for passive (ouabain-insensitive furosemide-insensitive) sodium efflux were similar in hypertensives and in normotensives. The cause of the reduced rate constant for ouabain-sensitive sodium efflux is not clear. However, as suggested for other types of altered erythrocyte transport mechanisms described recently, it might be determined genetically.


Clonal populations of CD4+ and CD8+ T cells in patients with multiple myeloma and paraproteinemia.
Patients with paraproteinemia have abnormalities in their T-cell subsets including inversion of the CD4:CD8 ratio and increased expression of activation markers. Recently, distortions in T-cell receptor (TCR) TCRAV and TCRBV gene segment expression have been reported, although the significance of these observations is unclear given the finding of clonal populations of CD8+ T cells in healthy elderly individuals. We have used an extensive range of TCR V-region-specific monoclonal antibodies to assess TCRAV and TCRBV expression in patients with myeloma and paraproteinemia. TCR sequence analysis was used to assess the clonality of expansions and 3-color fluorescence-activated cell sorting analysis determined the phenotype of the expanded populations. The patients show novel oligoclonal expansions within the CD4+ subset and show an increased frequency of CD8+ expansions. Oligoclonal CD4+ T cells belong to the rare CD4+CD28- T-cell subset, a phenotype associated with granular morphology. CD45RA and CD11b are expressed on many of the CD8 T-cell expansions. Comparison of T-cell receptor sequences from two T-cell clones in one patient suggests a possible role for a common peptide antigen in the generation of the expansions. Further work is needed to identify the relevance of such T cells to the B-cell proliferation.


Extravascular lung water measurements in acute respiratory distress syndrome: why, how, and when?
Increase in pulmonary vascular permeability accompanied with accumulation of excess extravascular lung water (EVLW) is the hallmark of acute respiratory distress syndrome (ARDS). Currently, EVLW and pulmonary vascular permeability index (PVPI) can be quantitatively measured using the transpulmonary thermodilution (TPTD) technique. We will clarify why, how, and when EVLW and PVPI measurements should be performed. Although the Berlin criteria of ARDS are simple and widely used, several criticisms of them have been published. The last 2 decades have witnessed the introduction and evolution of the TPTD technique for measuring EVLW and PVPI. Several publications have recommended to evaluate EVLW and the PVPI during the treatment of critically ill patients. Accurate and objective diagnoses can be made for ARDS patients using EVLW and PVPI. EVLW more than 10 ml/kg is a reasonable criterion for pulmonary edema, and EVLW more than 15 ml/kg for a severe condition. In addition to EVLW more than 10 mL/kg, PVPI more than three suggests increased vascular permeability (i.e., ARDS), and PVPI less than 2 represent normal vascular permeability (i.e., cardiogenic pulmonary edema). EVLW and PVPI measurement will open the door to future ARDS clinical practice and research, and have potential to be included in the future ARDS definition.


ISCOMATRIX adjuvant: an adjuvant suitable for use in anticancer vaccines.
Human Papillomavirus type 16 (HPV16) E6 and E7 oncoproteins are associated with cervical cancer development and progression and can therefore be used as target antigens for cancer immunotherapy. In this study we evaluated the immunogenicity in mice, of different vaccine formulations using recombinant HPV16 derived E6E7 or E7GST fusion proteins. When co-administered with ISCOMATRIX adjuvant, these E6E7 proteins consistently induced E7 specific CTL, in vivo tumor protection, antibody and DTH responses. ISCOMATRIX adjuvant has been developed for use in the formulation of novel human vaccines and has been evaluated for safety and toxicity in human trials. A formulation containing aluminum hydroxide (Al(OH)3) gave a lesser degree of E7 specific antibody, and no local E7 specific CTL response but similar DTH and tumor protection. These findings demonstrate the potential of ISCOMATRIX adjuvant to stimulate both cellular and humoral immune responses to endogenously processed target antigens, and hence is the preferred adjuvant when CTL responses are desirable.


Autophagy activation by rapamycin reduces severity of experimental osteoarthritis.
Osteoarthritis is associated with cell death and extracellular matrix degradation in articular cartilage. Autophagy is an essential cellular homeostasis mechanism that was found to be deficient in ageing and osteoarthritic cartilage. This study determined whether pharmacological inhibition of the mammalian target of rapamycin (mTOR), a key inhibitor of autophagy, has disease-modifying activity in experimental osteoarthritis. Experimental osteoarthritis was induced by transection of the medial meniscotibial ligament and the medial collateral ligament in 2-month-old C57Bl/6 mice (n=36). Rapamycin (1 mg/kg weight/day) (n=18 mice) or dimethyl sulphoxide vehicle control (n=18 mice) was administered intraperitoneally for 10 weeks. Histopathological changes in articular cartilage and synovium were examined by using semiquantitative scoring systems. Rapamycin effects on mTOR signalling, autophagy, cartilage homeostasis and inflammation were analysed by immunohistochemistry and immunofluorescence staining. Rapamycin affected the mTOR signalling pathway in mouse knee joints as indicated by the inhibition of ribosomal protein S6 phosphorylation, a target of mTOR and activation of LC3, a main marker of autophagy. The severity of cartilage degradation was significantly (p<0.01) reduced in the rapamycin-treated group compared with the control group and this was associated with a significant (p<0.05) decrease in synovitis. Rapamycin treatment also maintained cartilage cellularity and decreased ADAMTS-5 and interleukin-1β expression in articular cartilage. These results suggest that rapamycin, at least in part by autophagy activation, reduces the severity of experimental osteoarthritis. Pharmacological activation of autophagy may be an effective therapeutic approach for osteoarthritis.


Perspective: How to Develop Nutrient Profiling Models Intended for Global Use: A Manual.
Nutrient profiling (NP) models aim to assess the nutritional quality of individual foods, according to their energy content and nutrient composition. NP models, initially created to prevent obesity in high-income countries, have tended to penalize dietary energy by giving lower ratings to foods containing excessive calories, fat, sugar, and salt. Energy-driven NP models may need to be reconceptualized for use in low- and middle-income countries (LMIC) where hunger, undernutrition, and micronutrient deficiencies continue to be issues of public health concern. Consistent with the position of the WHO that the purpose of NP methods is to address an identified public health problem, NP models intended for use in LMIC ought to address inadequate intakes of vitamin A, B vitamins, folate, calcium, iron, iodine, and zinc and the frequent lack of high-quality protein. Those models of nutrient density that feature beneficial nutrients (high-quality protein, vitamins, minerals, and trace elements) may be better suited to LMIC needs than are some current NP models that are wholly based around nutrients to limit. NP models intended for LMIC and global use will also need to take food fortification into account. The challenge for LMIC public health agencies is how to balance the future risk of excess "empty" calories against the continuing danger of inadequate nutrients and micronutrient deficiencies that persist at the population level.


[Transitional laryngeal papilloma: clinical aspects, diagnosis and treatment].
Basing on the results of long-term observational study of 200 patients with laryngeal papillomatosis the authors made a conclusion on cycle pattern of the disease course. Each cycle consists of two periods: active (rapid growth of the tumor) and passive (slow growth of the tumor, recurrences are rare, 1-3 years of remission). A case of a male patient is reported illustrating cycle course of transitional laryngeal papilloma. In the beginning of the third cycle, in active period, his papilloma underwent malignant transformation. Cryotherapy of papilloma is thought ineffective.


Rasch analysis of the Brief Symptom Inventory-18 with African American and White students.
Although the United States offers some of the most advanced psychological services in the world, not everyone in the country shares these services equally, resulting in health disparities. Health disparities persist when assessments do not appropriately measure different populations' mental health problems. To address this assessment issue, we conducted principal axis factoring, confirmatory factor analysis, and Rasch analyses to assess the psychometric characteristics of the Brief Symptom Inventory-18 (BSI-18) to evaluate whether the BSI is culturally appropriate for assessing African American students' psychological distress. The dimensional structure of the BSI was first identified and held up under cross-validation with a second sample and a white sample. The measure was unidimensional among African American and white students. Our results suggested BSI in our samples presented characteristics such as low person separation, stability across samples, and little differential item functioning. Most African American and white students identified themselves on the low end of the categories in a 0-4 rating scale, indicating their low endorsement of the items on the BSI. Rasch analyses were completed with the original scale but also collapsing the scale to three points, with some increase in separation and reliability for the collapsed scale. As anticipated, differences in mean BSI scores were found for mental health-related variables. Implications for theory and research on multicultural health scales are discussed as are effects of item skewness on analyses. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Two-part survival models applied to administrative data for determining rate of and predictors for maternal-child transmission of HIV.
In analysing maternal-child HIV transmission from Medicaid claims data, we must deal with follow-up that is sometimes so short that we cannot claim that an apparently uninfected infant is actually uninfected as opposed to not yet exhibiting HIV-associated symptoms. To overcome this, we have been using analyses of 'time-to-diagnosis' of HIV infection to estimate transmission rates and predictors of transmission. Such analyses mix the event of transmission with that of our ability to diagnose HIV infection from coded claims data. We would like to separate these two pieces. Also, due to incomplete follow-up, Kaplan-Meier analyses will underestimate transmission rates. In econometrics and biostatistics there are two-part (mixture) models that can serve the goal of separating transmission from the process of diagnosing HIV infection in the newborn. Farewell describes a model that combines a logistic regression for the yes/no event (in our case, HIV transmission) and a Weibull regression model for the survival analysis portion (in our case, time-to-diagnosis). We use this approach to fit models that have potentially separate covariates for transmission and for time-to-diagnosis. The results allow us to identify predictors of transmission and estimate transmission rates with reduced concern for adequacy of follow-up.


Prebiotics in chronic intestinal inflammation.
Prebiotics are nondigestible fermentable fibers that are reported to have health benefits for the host. Older as well as more recent studies show beneficial effects in experimental colitis and lately also in human inflammatory bowel diseases (IBD), such as Crohn's disease, ulcerative colitis, and chronic pouchitis. In this review we give an overview of the benefits of prebiotics in rodent IBD models and in IBD patients and discuss their possible protective mechanisms. Commensal intestinal bacteria induce and perpetuate chronic intestinal inflammation, whereas others are protective. However, most of the current medications are directed against the exaggerated proinflammatory immune response of the host, some of them toxic and costly. Feeding prebiotics changes the composition of the intestinal microflora toward more protective intestinal bacteria and alters systemic and mucosal immune responses of the host. Therapy for IBD targeting intestinal bacteria and their function is just emerging. Prebiotics have the promise to be relatively safe, inexpensive, and easy to administer. Unraveling their protective mechanisms will help to develop rational applications of prebiotics. However, the initial promising results with dietary prebiotics in preclinical trials as well as small studies in human IBD will need to be confirmed in large randomized controlled clinical trials.


Test-retest reliability of four computerized neurocognitive assessment tools in an active duty military population.
Computerized neurocognitive assessment tools (NCATs) are increasingly used for baseline and post-concussion assessments. To date, NCATs have not demonstrated strong test-retest reliabilities. Most studies have used non-military populations and different methodologies, complicating the determination of the utility of NCATs in military populations. The test-retest reliability of four NCATs (Automated Neuropsychological Assessment Metrics 4 [ANAM4], CNS-Vital Signs, CogState, and Immediate Post-Concussion Assessment and Cognitive Test [ImPACT]) was investigated in a healthy active duty military sample. Four hundred and nineteen Service Members were randomly assigned to take one NCAT and 215 returned after approximately 30 days for retest. Participants deemed to have inadequate effort during one or both testing sessions, according to the NCATs scoring algorithms, were removed from analyses. Each NCAT had at least one reliability score (intraclass correlation) in the "adequate" range (.70-.79), only ImPACT had one score considered "high" (.80-.89), and no scores met "very high" criteria (.90-.99). However, overall test-retest reliabilities in four NCATs in a military sample are consistent with reliabilities reported in the literature and are lower than desired for clinical decision-making.


Activity during unemployment and mental health.
The main purpose of this study was to investigate activity during unemployment and the relationship between such activity and mental health in a sample (n = 213) of unemployed Norwegians. The results indicate that the unemployed are generally more passive than the average population, and that they are considerably less involved in social activities. However, the unemployed do not constitute a homogeneous group in terms of activity level and activity profile. Women were somewhat more active that men, particularly in connection with domestic chores. Young people were more active than the other age groups, particularly in connection with extra-familial activities. Several significant relationships were found between different activity categories and mental health. The more active the unemployed were, the better their mental health. The results are discussed in relation to similar data for the average population, other unemployment research, subjective and objective factors which can be of importance to the activity level and profile of the unemployed, sex role issues, theoretical models developed to explain and understand the effects of unemployment, methodological considerations, and the possible functions of activity for mental health.


Age differences in arterial and venous extra-cerebral blood flow in healthy adults: contributions of vascular risk factors and genetic variants.
Sufficient cerebral blood flow (CBF) and venous drainage are critical for normal brain function, and their alterations can affect brain aging. However, to date, most studies focused on arterial CBF (inflow) with little attention paid to the age differences in venous outflow. We measured extra-cerebral arterial and venous blood flow rates with phase-contrast MRI and assessed the influence of vascular risk factors and genetic polymorphisms (ACE insertion/deletion, COMT val158met, and APOEε4) in 73 adults (age 18-74 years). Advanced age, elevated vascular risk, ACE Deletion, and COMT met alleles were linked to lower in- and outflow, with no effects of APOE ε4 noted. Lower age-related CBF rate was unrelated to brain volume and was observed only in val homozygotes of COMTval158met. Thus, in a disease-free population, age differences in CBF may be notable only in persons with high vascular risk and carriers of genetic variants associated with vasoconstriction and lower dopamine availability. It remains to be established if treatments targeting alleviation of the mutable factors can improve the course of cerebrovascular aging in spite of the immutable genetic influence.


TGF-β loaded exosome enhances ischemic wound healing in vitro and in vivo.
Rationale: With over seven million infections and $25 billion treatment cost, chronic ischemic wounds are one of the most serious complications in the United States. The controlled release of bioactive factor enriched exosome from finbrin gel was a promising strategy to promote wound healing. Methods: To address this unsolved problem, we developed clinical-grade platelets exosome product (PEP), which was incorporate with injectable surgical fibrin sealant (TISSEEL), to promote chronic wound healing and complete skin regeneration. The PEP characterization stimulated cellular activities and in vivo rabbit ischemic wound healing capacity of TISSEEL-PEP were performed and analyzed. Results: PEP, enriched with transforming growth factor beta (TGF-β), possessed exosomal characteristics including exosome size, morphology, and typical markers including CD63, CD9, and ALG-2-interacting protein X (Alix). In vitro, PEP significantly promoted cell proliferation, migration, tube formation, as well as skin organoid formation. Topical treatment of ischemic wounds with TISSEEL-PEP promoted full-thickness healing with the reacquisition of hair follicles and sebaceous glands. Superior to untreated and TISSEEL-only treated controls, TISSEEL-PEP drove cutaneous healing associated with collagen synthesis and restoration of dermal architecture. Furthermore, PEP promoted epithelial and vascular cell activity enhancing angiogenesis to restore blood flow and mature skin function. Transcriptome deconvolution of TISSEEL-PEP versus TISSEEL-only treated wounds prioritized regenerative pathways encompassing neovascularization, matrix remodeling and tissue growth. Conclusion: This room-temperature stable, lyophilized exosome product is thus capable of delivering a bioactive transforming growth factor beta to drive regenerative events.


The value of weighted views of the acromioclavicular joint. Results of a survey.
One hundred twelve practicing members of the American Shoulder and Elbow Surgeons in the United States and Canada were surveyed regarding use of weighted views of the acromioclavicular joint. They were also asked about treatment for hypothetical patients seen in the emergency department or office with grade II or III acromioclavicular separations. One hundred five physicians (94%) responded to the survey. Eighty-five members (81 %) did not recommend obtaining weighted views in the emergency department. Sixty members (57%) did not use weighted views, and the majority commented that weighted views had no influence on their decision-making regarding treatment. Forty-five members (43%) used weighted views, but most did not use the results of this test to determine surgical intervention. Physicians recommending weighted views averaged 21 years of practice, compared with 16 years for those who did not obtain weighted views. Only nine physicians (9%) had changed treatment on the basis of weighted views. The patient's arm dominance, work, or athletic status did not influence most surgeons' decision to perform surgery when weighted views revealed a grade III separation. We found no correlation between obtaining weighted views and performing surgical reconstruction for patients with grade III acromioclavicular separations.


Voltammetric detection of glutathione: an adsorptive stripping voltammetry approach.
A simple, sensitive, and rapid detection of glutathione by cyclic voltammetry using a bare glassy carbon electrode is reported in which glutathione forms a 1 : 1 complex compound with copper(ii) ions. This complex compound is adsorbed onto the electrode surface and undergoes electrochemical oxidation at a characteristic oxidation potential of ca. -0.20 V vs. the standard mercury/mercurous sulphate reference electrode, which is used to detect the glutathione concentration. The linear dynamic range is obtained for a glutathione concentration from 1 μM to 12.5 μM, and the sensitivity is found to be 0.1 ± 0.002 μA μM(-1). A low limit of detection (n = 3) of 0.14 μM and a precision of 1.8% are achieved using a simple, unmodified electrode. The robustness of the present methodology is demonstrated by the successful quantitative analysis of glutathione in the presence of cysteine.


Molecular mechanisms of antibody-mediated neutralisation of flavivirus infection.
Flaviviruses are a group of positive-stranded RNA viruses that cause a spectrum of severe illnesses globally in more than 50 million individuals each year. While effective vaccines exist for three members of this group (yellow fever, Japanese encephalitis, and tick-borne encephalitis viruses), safe and effective vaccines for several other flaviviruses of clinical importance, including West Nile and dengue viruses, remain in development. An effective humoral immune response is critical for protection against flaviviruses and an essential goal of vaccine development. The effectiveness of virus-specific antibodies in vivo reflects their capacity to inhibit virus entry and spread through several mechanisms, including the direct neutralisation of virus infection. Recent advances in our understanding of the structural biology of flaviviruses, coupled with the use of small-animal models of flavivirus infection, have promoted significant advances in our appreciation of the factors that govern antibody recognition and inhibition of flaviviruses in vitro and in vivo. In this review, we discuss the properties that define the potency of neutralising antibodies and the molecular mechanisms by which they inhibit virus infection. How recent advances in this area have the potential to improve the development of safe and effective vaccines and immunotherapeutics is also addressed.


Molecular biology of macrophage colony-stimulating factor.
In this chapter we have described one of the more complex hemopoietic factors, M-CSF. The single-copy M-CSF gene is almost 21 kb in length and is arranged into 10 exons and 9 introns. Expression of the gene at the RNA level is heterogeneous, and several species of M-CSF mRNA have been found in human and murine cells and tissues. In human cells the different mRNAs arise from alternative splicing of the nuclear RNA precursor in both coding and noncoding regions. This results in mRNAs encoding two distinct M-CSF proteins, 256 and 554 amino acids in length. In murine cells only a 552-amino-acid form has been found thus far. All forms of M-CSF have a 32-amino-acid signal peptide and a 23-amino-acid hydrophobic region near the carboxy-terminus, which resembles a transmembrane domain. A large portion of the carboxy-terminal end, including the hydrophobic region, is not found in the mature protein. Thus, the primary translation product of M-CSF is a prepropolypeptide, with processing occurring at both amino- and carboxy-terminal ends. The exact size of the mature protein is still somewhat in doubt, but deletion mutagenesis from the carboxy-terminal end indicates that the protein may be as small as 150 amino acids and still be functional. Site-directed mutagenesis has also shown that the first seven cysteines in the mature molecule are probably necessary for biological activity, whereas the next two cysteine residues are not. In spite of the heavy glycosylation found in the native protein, removal of the N-linked glycosylation signals does not seem to affect activity to any great degree. The M-CSF gene and its receptor, C-FMS, are tightly linked on the long arm of chromosome 5, a unique finding in the ligand/receptor field. This region also contains the genes for GM-CSF, IL-3, ECGF, and the receptor for PDGF. A similar situation may exist on chromosome 11 of the mouse. The close linkage of these factors and receptors is the probable cause for the disorders of hemopoiesis that arise when deletions occur in this area. The preceding discussion has shown how quickly the area of M-CSF molecular biology has advanced in the past 2-3 years. A great deal of effort is now being directed toward expressing M-CSF at high levels in a variety of prokaryotic and eukaryotic systems.(ABSTRACT TRUNCATED AT 400 WORDS)


Induction of hematopoietic differentiation of mouse embryonic stem cells by an AGM-derived stromal cell line is not further enhanced by overexpression of HOXB4.
Hematopoietic differentiation of embryonic stem (ES) cells can be enhanced by co-culture with stromal cells derived from hematopoietic tissues and by overexpression of the transcription factor HOXB4. In this study, we compare the hematopoietic inductive effects of stromal cell lines derived from different subregions of the embryonic aorta-gonad-mesonephros tissue with the commonly used OP9 stromal cell line and with HOXB4 activation. We show that stromal cell lines derived from the aorta and surrounding mesenchyme (AM) act at an earlier stage of the differentiation process compared with the commonly used OP9 stromal cells. AM stromal cells were able to promote the further differentiation of isolated brachyury-GFP(+) mesodermal cells into hematopoietic progenitors, whereas the OP9 stromal cells could not support the differentiation of these cells. Co-culture and analyses of individual embryoid bodies support the hypothesis that the AM stromal cell lines could enhance the de novo production of hematopoietic progenitors, lending support to the idea that AM stromal cells might act on prehematopoietic mesoderm. The induction level observed for AM stromal cells was comparable to HOXB4 activation, but no additive effect was observed when these 2 inductive strategies were combined. Addition of a γ-secretase inhibitor reduced the inductive effects of both the stromal cell line and HOXB4, providing clues to possible shared molecular mechanisms.


The SpmA/B and DacF proteins of Clostridium perfringens play important roles in spore heat resistance.
Strains of Clostridium perfringens that cause acute food poisoning have been shown to produce spores that are significantly more heat resistant than those of other strains. Previous studies demonstrated that the spore core density and the ratio of spore cortex peptidoglycan relative to the germ cell wall were factors that correlated with the heat resistance of a C. perfringens spore. To further evaluate these relationships, mutant strains of C. perfringens SM101 were constructed with null mutations in dacF, encoding a D,D-carboxypeptidase, and in the spmA-spmB operon, which is involved in spore core dehydration. The dacF mutant was shown to produce less spore cortex peptidoglycan and had a corresponding decrease in spore heat resistance. The spmA-spmB strain produced highly unstable spores with significantly lower core densities and increased heat sensitivity, which were easily destroyed during treatments affecting the spore coat layers. These results support the previous assertion that a threshold core density as well as a high ratio of cortex peptidoglycan relative to the germ cell wall contribute to the formation of a more heat-resistant spore in this species.


[DNA-methylase from Arthrobacter luteus screens DNA from the action of site-specific endonuclease Alu I].
DNA-methylase was isolated from a cell extract of A. luteus and partially purified by chromatography on phosphocellulose. The purified enzyme methylates DNA of phage lambda and plasmids pBr322, thus making them resistant to a subsequent action of endonuclease Alu I. It has been shown that cytosine is the object of methylation within DNA. This modification does not screen DNA from the action of site-specific endonucleases Sal I, Bam HI, EcoR I, EcoR II, Xho I and Xho II. It has been experimentally demonstrated that the isolated methylase is site-specific and identifies in the DNA the nucleotide sequence 5'-AGCT-3', by methylating cytosine in the DNA.


Prevalence of smoking in adults with chronic pain.
Cigarette smoking is common among adults with chronic pain. The primary objective of this study was to determine the period prevalence of smoking in patients with chronic pain. A secondary objective was to determine the prevalence of smoking among patients with commonly occurring pain diagnoses including fibromyalgia, low back pain, and headache. This population study included 5350 patients (1256 smokers, 4094 nonsmokers) admitted to the Mayo Comprehensive Pain Rehabilitation Center from January 1998 through December 2012. Smoking status was determined using a self-report questionnaire. During the 15 year study period, the overall prevalence of smoking was 23.5 % (95 % CI 22.4 - 24.6). The prevalence of smoking in 2000, 2005, and 2010 was 24.2, 25.7, and 28.3 % respectively. The overall prevalence of smoking in patients with fibromyalgia, low back pain, and headache was 25.2 % (95 % CI 22.8 - 28.3), 22.8 % (95 % CI 21.3 - 25.9), and 21.2 % (95 % CI 17.9 - 24.7), respectively. In a multiple variable logistic model adjusted for age and sex, opioid use was significantly associated with status as a current smoker. The prevalence of smoking in patients with chronic pain has not declined when compared to the general population. The higher prevalence of smoking was consistently observed in commonly occurring pain diagnoses including fibromyalgia, back pain, and headache. Further research is needed to identify the potential factors that contribute to the high prevalence of smoking in this patient population.


Research advisory board members' contributions and expectations in the USA.
This study focuses on the Implementation Community Collaborative Board (I-CCB) to identify members' anticipated contributions to and returns from the I-CCB; examine whether or not members achieved these contributions and returns over time; and explore barriers and facilitators that influenced accomplishments. Longitudinal study with repeated semi-structured in-depth interviews; baseline captured anticipated contributions and returns; 6- and 18-month follow-ups short- and longer-term achievements. We used content analysis to code/reduce text into variables, describe, count and compare categories. Participants anticipated involvement in I-CCB dynamics/governance and in research tasks/procedures. Anticipated returns included social support. Participants exerting influence on I-CCB's research agenda stayed the same over time. Participants conducting research doubled between follow-ups; those writing grant proposals increased by 50%. Participants receiving emotional support remained the same. Challenges: meetings steered by researchers; lack of time; use of jargon. Facilitators: outreaching to community; being affected by HIV; having overlapping identities/roles as researcher, service consumer and/or practitioner. Research partners can maximize facilitators, redress barriers and improve advisory board members' retention. Findings may help optimize the functioning of advisory boards worldwide.


Dyadic concordance among prostate cancer patients and their partners and health-related quality of life: does it matter?
Serious and chronic illnesses occur within a family context, affecting not only the patient but also the spouse/partner, children and extended family network. Spouses/partners are likely to experience the greatest personal impact, and may influence patient adjustment. Also, the intimate relationship may be affected by the illness experience. This study examined whether dyadic concordance on the characteristics of prostate cancer (PC) was related to health-related quality of life (HRQOL), psychological distress and marital adjustment in PC patients and their female partners. Couples (N=164) completed questionnaires on the appraisals of PC, and individual and dyadic adjustment. Patient and partner PC appraisal ratings were positively correlated. There was a general pattern of patients and partners in concordant dyads, versus those in dyads in which spouses maximised or minimised PC characteristics, reporting significantly better individual HRQOL outcomes, although there were several exceptions. Patient-partner appraisal (dis)agreement generally did not significantly predict dyadic adjustment. Overall, results suggest that dyadic disagreement is associated with worse HRQOL in couples facing PC.


Antibodies to Bordetella pertussis in human colostrum and their protective activity against aerosol infection of mice.
Colostrum samples from Indonesian mothers were assayed for antibodies which agglutinate Bordetella pertussis and for antibodies to the filamentous hemagglutinin and the lymphocytosis-promoting factor of B. pertussis. Agglutinins were assayed by a microtiter method, and 36 of 58 samples tested (62%) had titers above 1:10 (range, less than 1:10 to 1:160). An enzyme-linked immunosorbent assay detected anti-filamentous hemagglutinin in 39 of 60 samples (65%) and anti-lymphocytosis-promoting factor in 26 of 60 samples assayed (43%). A total of 52 samples (87%) were positive for at least one of these antibodies. Pooled colostrum samples were separated by affinity chromatography into fractions enriched secretory immunoglobulin A (sIgA) or IgG and examined for their ability to passively protect suckling mice from aerosol challenge with B. pertussis. Samples (160 micrograms of protein) were given intraperitoneally 90 min before challenge. Death, rate of gain in body weight, and leukocytosis were used as indicators of illness. Colostrum containing anti-lymphocytosis-promoting factor or agglutinins was protective, whereas colostrum lacking these but containing anti-filamentous hemagglutinin gave little protection. The sIgA-enriched and IgG-enriched fractions appeared to be equal in their ability to protect against respiratory challenge with B. pertussis.


Mediastinal seminoma presenting as superior vena cava syndrome and tracheal obstruction.
Malignant germ cell tumours of the mediastinum are rare, presenting mostly in young males. These are bulky tumours, mostly intrathoracic, infiltrating into adjacent structures early in the growth process. Patients may present with symptoms of compression. Occasionally, mediastinal adenopathy and superior vena cava (SVC) syndrome may occur. We discuss a case of a 19 year old boy with six weeks history of progressively worsening shortness of breath and mid-sternal chest heaviness and one month history of swelling of the face and upper limbs. The entire face and upper extremities were grossly oedematous with engorged veins suggesting SVC syndrome. CT scan chest showed a large mediastinal mass 18 x 24 cm extending from the superior mediastinum to the mid pericardial area. The trachea was extrinsically compressed to almost 80% at its distal portion. Mass was resected completely. Post operative course was unremarkable. The final histopathology showed a fibrotic mass with no viable tumour. Surgery followed by radiation therapy has been the usual initial treatment with multimodal chemotherapy showing remarkable results.


Toll-like receptor 4-induced IL-22 accelerates kidney regeneration.
AKI involves early Toll-like receptor (TLR)-driven immunopathology, and resolution of inflammation is needed for rapid regeneration of injured tubule cells. Notably, activation of TLRs also has been implicated in epithelial repair. We hypothesized that TLR signaling drives tubule regeneration after acute injury through the induction of certain ILs. Systematic screening in vitro identified IL-22 as a candidate proregeneratory factor in primary tubular cell recovery, and IL-22 deficiency or IL-22 blockade impaired post-ischemic tubular recovery after AKI in mice. Interstitial mononuclear cells, such as dendritic cells and macrophages, were the predominant source of IL-22 secretion, whereas IL-22 receptor was expressed by tubular epithelial cells exclusively. Depleting IL-22-producing cells during the healing phase impaired epithelial recovery, which could be rescued entirely by reconstituting mice with IL-22. In vitro, necrotic tubular cells and oxidative stress induced IL-22 secretion selectively through TLR4. Although TLR4 blockade during the early injury phase prevented tubular necrosis and AKI, TLR4 blockade during the healing phase suppressed IL-22 production and impaired kidney regeneration. Taken together, these results suggest that necrotic cell-derived TLR4 agonists activate intrarenal mononuclear cells to secrete IL-22, which accelerates tubular regeneration and recovery in AKI.


The role of patients' stories in medicine: a systematic scoping review.
Patients' stories provide Palliative Care physicians with a glimpse into the former's lives and their psycho-emotional, sociocultural, and contextual considerations. Yet, few physicians are trained to interpret and apply patients' stories in their practice. Inherent variability in how stories are transmitted and interpreted raises questions over their potential effects on care. Amidst a dearth of accounts in Palliative Care, we map current use of patient stories to guide the training, assessment, and oversight of this 'care influencing' practice in medicine. This systematic scoping review was guided by the Systematic Evidence-Based Approach (SEBA) to ensure a reproducible and structured approach. The themes and categories identified through the Split Approach's concurrent and independent thematic and directed content analyses provided a comprehensive sketch of the included articles. The Jigsaw Perspective combined the themes and categories identified. The last stage of SEBA compared these results with two recent reviews of storytelling to ensure consistency of the domains created that guided the discussion. Ten thousand two hundred seven articles were reviewed, 963 full text articles were evaluated, and 199 articles were included. The four domains identified were study characteristics, benefits, approaches, and positive effects and concerns. Stories support patient-centered, personalized, and holistic clinical care. However, variability in the stories, their interpretations and use in care decisions underscore the need for further study on the structuring, teaching, assessing, and delivery of this 'care influencing' practice.


Influence of unilateral eyelid spasms and botulinum toxin treatment on intraocular pressure measured by transpalpebral tonometer.
Eyelid spasms might be associated with elevated intraocular pressure (IOP) in hemifacial spasm (HFS) patients. IOP assessment using a Goldmann applanation tonometer (GAT) is often compromised by eyelid spasms. This study aimed to assess the effect of HFS on IOP measurements using the transpalpebral tonometer Diaton® before and after treatment with botulinum toxin type A (BTX-A) and compared Diaton® and GAT measurements after treatment with BTX-A. IOP measurements were obtained with Diaton® in 27 patients with moderate-to-severe HFS before and after treatment with BTX-A. After treatment, the IOP was also measured using GAT and the results were compared with the ones measured with a Diaton®. The patients underwent automated perimetry, OCT, and pachymetry for screening to glaucoma. Mean IOP with Diaton® was 11 ± 3.42 mmHg before treatment in the affected eye and 9 ± 2.98 mmHg in the contralateral eye. This difference was statistically significant (P = 0.012). However, after treatment with BTX-A, no interocular difference was found in IOP obtained with Diaton® (P = 0.204) or GAT (P = 0.971). Comparison between GAT and Diaton® measurements showed no significant differences after BTX-A treatment between the affected (P = 0.212) and contralateral eye (P = 0.971). A significant reduction in IOP measurements on the affected side of HFS patients was observed after treatment with BTX-A, demonstrating that eyelid spasms may increase the IOP. No significant difference was observed between Diaton® and GAT measurements after the application of BTX-A. No differences were found in automated perimetry, OCT, and CCT when comparing affected eyes with contralateral eyes.


Functional connectivity analysis of cortical networks in Functional Near Infrared Spectroscopy using phase synchronization.
Functional Near Infrared Spectroscopy (fNIRS) is a non invasive functional neuroimaging method used for studying brain activity using blood oxygen level dependent (BOLD) signal. We use phase synchronization between fNIRS channels to detect functional connections between brain regions in a speech study. Data is collected from 22 neonates whose brain activity was monitored by fNIRS while being exposed to two different types of auditory stimuli. The wavelet based phase locking analysis reveals functional connections between temporal regions and most other regions in general and frontal areas in particular.


Low permeability asphalt concrete gamma ray shielding properties.
Energy-dependent gamma ray shielding properties were measured as a function of gamma ray energy for a low permeability asphalt concrete that is used as a cap to prevent water infiltration into radioactive waste sites. Experimental data were compared to ISO-PC point kernel shielding calculations. Calculated dose equivalent rates compared well with experimental values, especially considering the poor detector resolution involved. The shielding properties of the asphalt concrete closely resembled those of aluminum. The results presented can be used to determine the asphalt concrete thickness required to reduce dose equivalent rates from several gamma ray emitting radionuclides.


Sickness absence frequency among women working in hospital care.
Frequent short sickness absences result in understaffing and interfere with work processes. We need more knowledge about factors associated with this type of absence. To investigate associations between the frequency of previous sickness absence and self-reported perceptions of health and work. Cross-sectional study of female hospital care workers in which health, work characteristics and coping styles were assessed by questionnaire and linked to the number of sickness absence episodes recorded in the preceding 5 years using negative binomial regression analysis for counts distinguishing between short (1-7 days) and long (>7 days) episodes of absence after adjusting for age and duration of employment in December 2007 and hours worked between 2003 and 2007. Of 350 women employed for at least 5 years, 237 (68%) answered the questionnaire. The hours worked over the 5 year period [rate ratio (RR) = 1.2] and problem solving coping style score (RR = 1.1) were positively associated with the number of short sickness absence episodes. Age (RR = 0.8) and good general health (RR = 0.7) were inversely related to the number of both short and long episodes. Self-reported mental health and work characteristics were not shown to be related to the frequency of sickness absence. Hours worked, problem-solving coping style, age and general health showed associations with the frequency of previous sickness absence among women who had worked at least 5 years in health care. Future prospective studies on the frequency of sickness absence should consider the impact of these factors further.


Contrasting patterns of polymorphism and divergence on the Z chromosome and autosomes in two Ficedula flycatcher species.
In geographic areas where pied and collared flycatchers (Ficedula hypoleuca and F. albicollis) breed in sympatry, hybridization occurs, leading to gene flow (introgression) between the two recently diverged species. Notably, while such introgression is observable at autosomal loci it is apparently absent at the Z chromosome, suggesting an important role for genes on the Z chromosome in creating reproductive isolation during speciation. To further understand the role of Z-linked loci in the formation of new species, we studied genetic variation of the two species from regions where they live in allopatry. We analyzed patterns of polymorphism and divergence in introns from 9 Z-linked and 23 autosomal genes in pied and collared flycatcher males. Average variation on the Z chromosome is greatly reduced compared to neutral expectations based on autosomal diversity in both species. We also observe significant heterogeneity between patterns of polymorphism and divergence at Z-linked loci and a relative absence of polymorphisms that are shared by the two species on the Z chromosome compared to the autosomes. We suggest that these observations may indicate the action of recurrent selective sweeps on the Z chromosome during the evolution of the two species, which may be caused by sexual selection acting on Z-linked genes. Alternatively, reduced variation on the Z chromosome could result from substantially higher levels of introgression at autosomal than at Z-linked loci or from a complex demographic history, such as a population bottleneck.


Primary progressive aphasia and the language network: the 2013 H. Houston Merritt Lecture.
Review of clinical and biological features of primary progressive aphasia (PPA). The PPA syndrome arises when language-dominant (usually left) hemisphere becomes the principal target of neurodegeneration. Depending on the distribution of neuronal loss within the language network, agrammatic (PPA-G), logopenic (PPA-L), and semantic (PPA-S) subtypes are identified. The most common underlying neuropathology is frontotemporal degeneration with tauopathy in PPA-G, frontotemporal degeneration with TDP-43 proteinopathy in PPA-S, and Alzheimer pathology in PPA-L. When Alzheimer pathology is detected, the neurofibrillary tangles show lower entorhinal-to-neocortical ratios and greater leftward asymmetry in PPA than in the typical amnestic dementia of Alzheimer disease. The ε4 allele of APOE, a major risk factor for Alzheimer pathology in amnestic dementias, is not a risk factor for Alzheimer pathology in PPA. These observations indicate that Alzheimer disease has biological variants with distinct patterns of lesion distribution and perhaps also molecular background. The selective vulnerability of the language network in PPA is likely to reflect complex interactions between factors that determine the type of histopathology, on one hand, and those that influence the resilience of the language network, on the other. A history of learning disability, including dyslexia, is emerging as one of the potential factors in this second group of determinants. Patient care in PPA should be individualized so that speech therapy can address the specific type of language impairment while pharmacologic therapy is directed to the underlying disease process.


Multi-residue analysis of pesticides in agricultural products by liquid chromatography time-of-flight mass spectrometry.
The applicability of liquid chromatography time-of-flight mass spectrometry (LC-TOF-MS) for determining pesticide residues in agricultural products was investigated. TOF-MS conditions for monitoring target ions, together with their fragment ions, were carefully optimized. The developed LC-TOF-MS method was evaluated for 154 pesticides in soybean and spinach by using matrix-matched standards. No significant matrix effect was observed for most of the tested pesticides at a concentration level of 0.01 mg/kg, where the limits of quantification were less than 0.01 mg/kg for 145 of the 154 pesticides (S/N>10). In addition, no significant interference was observed in the chromatograms of the blank extracts. These results indicate that LC-TOF-MS determination may become a powerful tool for multi-residue analysis of pesticides in agricultural products.


The surgical management for isolated scaphotrapeziotrapezoid (STT) osteoarthritis : a systematic review of the literature.
We performed a systematic review to find out the safety and efficacy of various procedures for isolated scaphotrapeziotrapezoid osteoarthritis. Eleven articles were included. The most common procedure was arthroplasty with pyrocarbon implant (28%), followed by resection of distal pole of scaphoid with proximal trapezium and trapezoid resection (18%). The other procedures included trapeziectomy with ligament reconstruction and tendon interposition (LRTI) (14%), arthroscopic resection of distal scaphoid (11%), trapezium and trapezoid resection with LRTI (10%) and arthrodesis (10%). Complications were noted in 18 (15%) patients. The most common complication (7.5%) was asymptomatic dorsal intercalated segmental instability (DISI) followed by dislocation of the pyrocarbon implant (3%). Fusion resulted in decreased range of motion and grip strength. The distal scaphoid resection was related to high rate of DISI. Although the pyrocarbon implant has a higher dislocation rate which requires revision surgery, this complication is avoidable with good surgical technique. Arthroplasty with pyrocarbon implant may be the first choice in younger patients.


Advanced stages of embryonic development and cotylocidial morphogenesis in the intrauterine eggs of Aspidogaster limacoides Diesing, 1835 (Aspidogastrea), with comments on their phylogenetic implications.
Ultrastructural aspects of the advanced embryonic development and cotylocidial morphogenesis of the aspidogastrean Aspidogaster limacoides are described. The posterior or distal regions of the uterus are filled with eggs containing larvae at advanced stages of morphogenesis and fully-formed cotylocidia. Various stages and organs of this larva are described in detail, including the aspects of the developing and fully-differentiated cotylocidium, the body wall (tegument and musculature), glandular regions and the protonephridial excretory system. Blastomere multiplication by means of mitotic divisions takes place simultaneously with the degeneration or apoptosis of some micromeres; this frequently observed characteristic is compared and discussed in relation to corresponding reports for other neodermatans. During the advanced stages of the embryonic development of A. limacoides, the vitelline syncytium disappears and the size of the embryo increases rapidly. Evident polarization of the differentiating larva was observed; towards one pole of the egg, cytodifferentiation of the mouth, surrounded by the oral sucker and cephalic glands, takes place, whereas, towards the opposite pole, differentiation of the posterior sucker (incipient ventral disc) occurs. The oral and posterior suckers are formed from numerous embryonic cells which have differentiated into myocytes. The central part of the oral sucker undergoes invagination and forms the future pharynx and intestine. Fully-developed cotylocidia of A. limacoides have a neodermatan type of tegument, flame cells and two types of glandular structures. These results suggest a sister relationship between the Aspidogastrea and the Digenea, although the systematic position of aspidogastreans in relation to other platyhelminth taxa remains somewhat equivocal.


Expression of specific binding sites on Candida with functional and antigenic characteristics of human complement receptors.
Receptors for C3 degradation fragments (CR1, CR2, and CR3) are present on many human cells including phagocytes and lymphoid cells and may be critical in the attachment of invading microorganisms. In these studies Candida were found to mimic the human CR by binding erythrocytes coated with specific human C3 fragments. Yeast forms of Candida species were adhered to glass slides and were allowed to germinate. Sheep erythrocytes (E) were coated with IgM (EA) and human complement components to prepare EA, EAC14, EAC3b, EAC3bi, and EAC3d. These test cells were then examined for adherence to the organism. Antibodies to human CR1, CR2, and CR3 were used to evaluate their potential for blocking adherence of the test erythrocytes to Candida. Fluorescein-labeled antibodies to human complement receptors were also used to characterize the binding sites. EAC3bi and EAC3d, but not E, EA, or EAC14, bound extensively to the germ tubes and pseudohyphae of Candida albicans and C. stellatoidea. EAC3b bound infrequently. Other Candida species, generally considered less pathogenic, bound significantly fewer specific test erythrocytes than C. albicans. Monoclonal antibodies to human CR1 and CR3 (3D9, 1B4, C511, 2B6, anti-B2, Mo1, and anti-Mac-1), in general, did not block adherence of test erythrocytes. Blocking of adherence of EAC3bi and EAC3d test erythrocytes coated with small quantities of C3 fragments occurred with high concentrations of monoclonal (anti-CR2) HB-5 and polyclonal (anti-CR2) anti-GP 140. Immunofluorescence studies demonstrated binding of Mo-1 to the germinated forms of the organism, whereas binding of the other antibodies was not seen. These studies suggest a surface constituent on the organism similar to CR on human cells. Additional studies are necessary to further define the molecular nature of the binding site. The ability of organisms to mimic human CR may be more generalized than previously known and may serve as a mechanism for modification of the inflammatory and immune response.


Duplex Doppler estimation of Pourcelot resistive index in arcuate arteries of sedated normal cats.
Renal failure is an important cause of morbidity and mortality in feline patients. In human patients, intrarenal blood flow values obtained with duplex Doppler ultrasonography have been used to aid in the diagnosis and prognosis of renal failure. The purpose of this report is to present values for resistance to intrarenal blood flow in normal cats, derived by duplex Doppler ultrasonography. Ten mature clinically healthy conditioned domestic shorthaired cats were screened for normal renal anatomy and function by CBC, serum biochemical profile, urinalysis, urine protein/creatinine ratio, endogenous creatinine clearance, and renal B-mode ultrasonography; and for normal systemic blood pressure with Doppler pressure cuff measurement. Subsequently, the cats were sedated with ketamine hydrochloride, and values for mean intrarenal (arcuate artery) resistance to blood flow were determined by duplex Doppler ultrasonography, and expressed as the Pourcelot resistive index, a ratio of systolic to diastolic flow commonly used in duplex Doppler sonography in human patients. After duplex Doppler sonographic examination, histological normalcy of the kidneys was verified by evaluation of ultrasound-guided percutaneous renal biopsy. Based on the obtained resistive indices, 95% confidence intervals for normal values were calculated as follows: left kidney, 0.52 to 0.60; right kidney, 0.55 to 0.63. No statistically significant difference was noted between the values obtained for the right versus the left kidney.


Lymphocyte Subset Reference Ranges in Healthy Israeli Adults.
Reference ranges for adult peripheral blood lymphocyte subsets have been established in a few countries. To the best of our knowledge no broad lymphocyte subset analysis of the Israeli population has been reported. Objectives: To establish reference ranges for healthy adults in Israel and to describe age- and gender-specific differences, if present. To establish reference ranges for healthy adults in Israel and to describe age- and gender-specific differences, if present. Lymphocyte subsets CD3, CD3/CD4, CD3/CD8, CD3-/CD16+/CD56+, CD3/TCRαβ, CD3/TCRγδ, and CD19 were examined by flow cytometry in 326 subjects. Samples were subdivided according to age and gender. Women of all ages had a significantly higher percentage and absolute counts of CD3/CD4 cells than their male counterparts. Higher CD3/CD4 cells were observed also in the older population (> 50 years). CD3/CD8 and CD3-/CD16+/CD56+ were higher in males. Older males had a lower total lymphocyte percentage and CD19 cells compared to younger men. No significant gender-related differences were observed in percent and number of CD19, CD3/TCRαβ or CD3/TCRγδ at all ages. These reference values could be useful in further studies for assessing changes that occur in different populations in human pathology.


Single-shot depth-section imaging through chromatic slit-scan confocal microscopy.
A chromatic confocal microscope constructed with a white-light source in combination with a diffractive lens provides wavelength-to-depth coding for profile measurements of a three-dimensional sample. We acquired depth-section images nonmechanically and in parallel by incorporating a slit-scan confocal technique into the system. A system using a 100x objective obtained a depth resolution of 0.023 mum comparable with surface profilometers that operate using conventional confocal microscopy. Experimental measurements of a four-phase-level diffractive element and of a machined, metal bearing are presented.


School diversity and racial discrimination among African-American adolescents.
The study presented here examined school context as a moderator in the relation between daily perceptions of racial discrimination and depressive symptoms. The sample included 75 Black adolescents who completed daily surveys for 14 days. The results indicated that approximately 97% of adolescents reported experiencing at least one discriminatory experience over the 2-week period. During the daily diary period, the 2-week average was 26 discriminatory experiences with a daily average of 2.5 discriminatory events. The results indicated perceptions of racial discrimination were linked to increased depressive symptoms on the following day. This relation was apparent for Black youth attending predominantly Black and White high schools, but not for Black youth attending schools with no clear racial majority.


Cohort study of Anticoagulation Self-Monitoring (CASM): a prospective study of its effectiveness in the community.
Trials show that oral anticoagulation therapy (OAT) substantially reduces thromboembolic events without an increase in major haemorrhagic events, but it is not known whether these results translate into routine practice. To estimate the current levels of control and adverse events in patients self-monitoring OAT, explore the factors that predict success, and determine whether the level of side effects reported from randomised controlled trials are translated to a non-selected population. Prospective cohort study in the UK. Participants were aged ≥18 years and registered with a GP. Main outcomes were the proportion of participants, over 12 months, who were still self-monitoring, had not experienced adverse events, and had achieved >80% of time in therapeutic range (TTR). In total, 296 participants were recruited; their median age was 61 years and 55.1% were male. Participants were predominately professional or held a university qualification (82.7%). At 12 months, 267 (90.2%) were still self-monitoring. Mean TTR was 75.3% (standard deviation 16.9).Six serious and two minor adverse events were reported by GPs. Only 45.9% of participants received any in-person training at the outset. Increased age (P = 0.027), general wellbeing (EQ-5D visual score, P = 0.020), and lower target international normalised range (INR, P = 0.032) were all associated with high (>80% TTR) levels of control. The findings show that, even with little training, people on OAT can successfully self-monitor, and even self-manage, their INR. TTR was shown to improve with age. However, widespread use of self-monitoring of INR may be limited by the initial costs, as well as a lack of training and support at the outset.


Pre-emption strategies to block taxes on sugar-sweetened beverages: A framing analysis of Facebook advertising in support of Washington state initiative-1634.
ABSTRACTIn 2018, the sugar-sweetened beverage (SSB) industry introduced a ballot measure (I-1634) in Washington State of the United States to prevent further local taxes on groceries. The measure, which passed, is emblematic of new pre-emptive legislative strategies by the SSB industry to block soda taxes and conceal those strategies under the guise of preventing burdensome 'grocery taxes'. This paper uses qualitative framing analysis to examine a public archive of 1218 Facebook advertisements to understand how I-1634 proponents shaped public discourse and engaged in misinformation efforts online during the lead up to the passage of I-1634. Coding strategies identified 7 compelling and inter-related framing strategies used by the campaign. These included strategies that misinformed the public about the threat of grocery taxation and the economic impacts it would have on the region. Strategies to conceal the true intent of the ballot measure and the sponsors of the campaign were aided by Facebook's advertising platform, which does not moderate misinformation in advertising and allows advertisers to conceal their sponsors. We urge public health researchers and advocates to pay more attention to how Facebook and other social media platforms can be used by industries to target voters, misinform publics, and misconstrue industry support.


Ethyl cellulose/gelatin/β-cyclodextrin/curcumin nanofibrous membrane with antibacterial and formaldehyde adsorbable capabilities for lightweight and high-performance air filtration.
Functionalization of bio-based nanofibers is the development tendency of high-performance air filter. However, the conventional structural optimization strategy based on high solution conductivity greatly hinders the development of fully bio-based air filter, and not conducive to sustainable development. This work fabricated fully bio-based nanofibrous membrane with formaldehyde-adsorbable and antibacterial capabilities by electrospinning low-conductivity solution for high-performance air filtration and applied to lightweight mask. The "water-like" ethyl cellulose (EC) was selected as the base polymer to "nourish" functional materials of gelatin (GE), β-cyclodextrin (βCD), and curcumin (Cur), thus forming a solution system with high binding energy differences and electrospinning into ultrafine bimodal nanofibers. The filtration efficiency for 0.3 μm NaCl particles, pressure drop, and quality factor were 99.25 %, 53 Pa, and 0.092 Pa-1, respectively; the bacteriostatic rates against Escherichia coli and Staphylococcus aureus were 99.9 % and 99.4 %, respectively; the formaldehyde adsorption capacity was 442 μg/g. This is the first report on antibacterial and formaldehyde-adsorbable high-performance air filter entirely made from bio-based materials. This simple strategy will greatly broaden the selection of materials for preparing high-performance multifunctional air filter, and promote the development of bio-based air filter.


Big epilepsy surgery for little people: what's the full story on hemispherectomy?
Hemispherectomy is the most dramatic type of brain resection performed for epilepsy. Introduced by McKenzie in 1938,(1) it is indicated for intractable seizures that predominantly first occur in infancy and early childhood, arise diffusely from one hemisphere, and are associated with unihemispheric insults. These include hemimegalencephaly, other multilobar cortical dysplasias, perinatal strokes, Sturge-Weber syndrome, and Rasmussen encephalitis. Improvements in surgical techniques and patient selection criteria have resulted in lower complication rates, including lower mortality. Because hemispherectomy is often performed in children who already have moderate to severe hemiplegia, the added motor deficits from the surgery are generally low. Furthermore, given the plasticity in the developing brain, surgery when done early may allow reorganization and preservation of both motor and cognitive function.


The anniversary year: Part III. The ACD role in dental journalism.
Thus, the challenge to proprietary dental journalism was made and corrective action presented. The Journal of Dental Research was identified as a model and given encouragement and support. The Journal of the American College of Dentists became a regular part of the dental literature. The College established formal relations with the American Association for the Advancement of Science and the College indirectly gave birth through the W.J. Gies Endowment Fund for the Journal of Dental Research to the William J. Gies Foundation for the Advancement of Dentistry, Inc. These actions crossed all disciplines of the dental profession and in the 1930's identified the College as an organization to be reckoned with for professional matters. J. Ben Robinson stated it very well in his Presidential Address on the afternoon of November 3rd, 1935: "The College, from its modest beginning fifteen years ago, has rapidly and substantially grown to occupy an important place in the profession. As its duty has become clearer, and its responsibilities better understood, additional problems have been accepted and assigned to committees for investigation, study and report. The ensuing results have contributed materially to the advancement of the profession by clarifying thought, establishing sound trends of endeavor, and strengthening the positions of dentistry in many important relations... The American College of Dentists exist for the prime purpose of fostering professionalism as an ideal, and of promoting education, literature, and organization along lines that will ensure high standards in all relations....(ABSTRACT TRUNCATED AT 250 WORDS)


Laboratory sleep patterns and dream content of type A and B scoring college students.
The suggestion that there may be a discrepancy between subjective and objective measures of sleep led us to explore the sleep and dreams of 7 Type A and 7 Type B scorers in our laboratory over a three-night period. In earlier studies, Type A scorers had indicated that their sleep was somewhat more disturbed and their dream content generally more active and negative in tone than that of Type B scorers. However, in this study the only differences were that Type A scorers had a greater number of body movements and greater dream recall than did Type B scorers. These results seem to indicate that the impression Type A scorers have of the quality of their sleep and dreams may be a function of their waking life-style.


Artemisinin loaded chitosan magnetic nanoparticles for the efficient targeting to the breast cancer.
Artemisinin, a natural anti-malarial agent, also possesses anti-proliferative and anti-angiogenic activity in cancer cells with very low toxicity to normal healthy cells. Drug loaded magnetic nanoparticles by using external magnetic field could selectively accumulate the drug at the target site and thereby reduce the doses required to achieve therapeutic concentration which may otherwise produce serious side effects on healthy cells. In the present study the artemisinin magnetic nanoparticles were successfully formulated using chitosan by ionic-gelation method. The developed magnetic nanoparticles of artemisinin were smooth and spherical in nature and their size was in the range of 349-445nm. The polydispersity index (PDI) and zeta potential of the formulated nanoparticles were in the range of 0.373-0.908 and -9.34 to -33.3 respectively. They showed 55% to 62.5% of drug encapsulation efficiency and 20% to 25% drug loading capacity. Around 62% to 78% of artemisinin was released from the artemisinin magnetic nanoparticles over the period of 48h. On application of physiologically acceptable external magnetic field, FITC conjugated artemisinin magnetic nanoparticles showed an enhanced accumulation of nanoparticles in the 4T1 breast tumour tissues of BALB/c mice model.


Restoration and reinforcement of endodontically treated teeth with a polyethylene ribbon and prefabricated fiberglass post.
In the past it was considered appropriate to place a cast post and core in every pulpless tooth without regard to the remaining supportive tooth structure present. Recent research and the advent of adhesive bonding techniques have caused clinicians to reevaluate their restorative protocol. This article reviews the current literature with regard to restoration of the endodontically treated tooth and presents a method for restoration and reinforcement utilizing a combination of polyethylene ribbon and a prefabricated fiberglass post.


Two cases of glomerulonephritis in one patient infected with the hepatitis C virus.
Membranoproliferative glomerulonephritis (GN) may be pathogenically associated with infection due to the hepatitis C virus (HCV) as many clinical cases have shown. The potential relationship between the HCV and IgA GN, by contrast, has been suggested only in isolated cases. IgA nephropathy recurs in up to 50% of cases after renal transplantation, but it is uncommon for it to appear as a de novo GN. We report the case of a patient with chronic infection due to the HCV and liver disease, who developed two different glomerular diseases during its progression: membranoproliferative GN in his native kidneys, a process that caused terminal renal failure and de novo IgA GN in the transplanted kidney. The potential pathogenic relationship of both glomerular processes with infection due to the HCV is discussed.


Effect of infrared-assisted spouted bed drying of flaxseed on the quality characteristics of its oil extracted by different methods.
Infrared (IR)-assisted spouted bed drying (SBD) has emerged as a potential alternative to the traditional hot air drying for heat sensitive components. The aim of this study was to investigate effect of IR-assisted SBD and application of cold press (CP), solvent extraction (SE) and ultrasound assisted extraction (UAE) on the quality of flaxseed oil. SBD and IR-assisted SBD were performed at air temperatures of 40, 60, 80 °C and their effects on the drying rate, fatty acids composition and oil peroxide and acid values were evaluated. Quality of oil extracted from the dried flaxseeds by CP, SE and UAE methods was then evaluated. Increasing air temperature in the presence of IR increased the drying rate. The peroxide values (PVs) of IR-SBD samples were higher than those of SBD at the same temperature. IR treatment did not notably change the composition of fatty acids in flaxseed oil, except in linoleic acid content. UAE gave higher extraction yield than CP and SE methods. UAE yielded an oil with higher percentage of saturated fatty acids, whereas the percentage of omega-3 and omega-6 fatty acids was higher in the CP method. The oil extracted by CP exhibited lower levels of PV (0.516 meq O2 /kg oil) and acid value (1.36%), as compared to oils extracted by SE and UAE methods. Both UAE and conventional methods did not significantly influence the composition of fatty acids in the extracted oils. Nonetheless, the CP method yielded an oil with a high percentage of omega-3 and omega-6 fatty acids. © 2019 Society of Chemical Industry.


Mechanical and structural correlates of canine pericardium.
We have assessed viscoelastic properties of pericardium within the physiological range of stresses and related mechanical behavior to fiber direction as defined by scanning electron microscopy. Stiffness, stress relaxation, and creep were measured in samples taken from the anterior surface of 14 canine pericardia. Stress-strain relations generally were not exponential; stiffness at a stress of 1 g/mm2 ranged from 12.9 to 239 g/mm2 during stretch and varied both from pericardium to pericardium and with the orientation of the strip within the sample (anisotropy). The strips exhibited hysteretic behavior which was not promotional to rate of strain. Following a rapid increase in stress, creep averaged less than 1% and stress relaxation, 34% in a 30-minute test period. The orientation of the strip with the greatest stiffness was consistent from pericardium to pericardium, and correlated with a layer of collagen fibers oriented along the major axis of te strip.


Mortality of babies enrolled in a community-based support programme: CONI PLUS (Care of Next Infant Plus).
To report mortality in babies enrolled on a community-based programme, Care of Next Infant Plus (CONI PLUS), which primarily supports parents anxious because of previous sudden unexpected death in infancy (SUDI) in their extended family or following an apparent life threatening event (ALTE) in their baby. Prospective observational study from 1996 to 2010 in the UK. Of 6487 babies enrolled, 37 died (5.7 per 1000). There were 2789 (43.0%) SUDI related babies of whom, six died suddenly and unexpectedly (2.15 per 1000). Four babies were sharing a sofa at night or a bed with parent(s) who smoked or had consumed alcohol. Of the 1882 (29.0%) babies enrolled following an ALTE, five died suddenly and unexpectedly (2.66 per 1000): four unexplained and one due to infection. None occurred while sharing a sleep surface, and at least three died during the day. The remaining 1816 (28%) babies were enrolled for other reasons. Seven died suddenly and unexpectedly (3.85 per 1000), two were unexplained and none associated with bed sharing. The number of SUDI deaths in babies enrolled on CONI PLUS is higher than expected from UK averages. Deaths in babies enrolled because of family history of SUDI were mostly associated with inappropriate sharing of a sleep surface at night and mostly outside the peak age range for sudden infant death. The opposite is true for those enrolled following an ALTE. The number of deaths is small but findings suggest a different mechanism for death in these two groups.


Effects of anthropogenic disturbance and climate on patterns of bat fly parasitism.
Environmental conditions, including anthropogenic disturbance, can significantly alter host and parasite communities. Yet, our current knowledge is based mainly on endoparasites, while ectoparasites remain little studied. We studied the indirect effects of anthropogenic disturbance (human population density) and climate (temperature, precipitation and elevation) on abundance of highly host-specific bat flies in four Neotropical bat species across 43 localities in Venezuela. We formulated a set of 11 a priori hypotheses that included a combination of the two effectors and host species. Statistically, each of these hypotheses was represented by a zero-inflated negative binomial mixture model, allowing us to control for excess zeros in the data. The best model was selected using Akaike's information criteria. Fly abundance was affected by anthropogenic disturbance in Artibeus planirostris, Carollia perspicillata and Pteronotus parnellii, but not Desmodus rotundus. Climate affected fly abundance in all bat species, suggesting mediation of these effects via the host or by direct effects on flies. We conclude that human disturbance may play a role in shaping bat-bat fly interactions. Different processes could determine fly abundance in the different bat species.


Effect of personal, food manufacturer, and pet health statements made by a veterinarian during a pet wellness appointment on a dog or cat owner's decision to consider changing their pet's diet.
To investigate the effect of statements made by veterinarians during a pet wellness appointment on a pet owner's decision to consider changing their pet's diet. Pet owners who presented their dogs and cats for wellness examinations from December 2018 to February 2019 to a veterinary medical teaching hospital or an affiliated low-cost community clinic. Pet owners completed part 1 of the survey, which included questions on various pet characteristics (eg, signalment and current diet) and pet owner's degree of satisfaction with their pet's diet, after a veterinary medical student obtained the pet's medical history and examined the pet. At the conclusion of the wellness appointment, owners completed part 2, which included pet owner demographics (eg, gender and highest educational level) and statements regarding personal, food manufacturer, and pet health that could be made by a veterinarian regarding a pet's diet to which owners were asked to react. 84 dog and 36 cat owners completed the survey. Statements based on pet health and personal (veterinarian) preferences were the most and least effective, respectively, on owners to consider changing their pet's diet. Pet owner gender and pet species did not alter the findings. Most (93%) pet owners were at least somewhat willing to change their pet's diet on the basis of a veterinarian's recommendation. When a pet's diet is discussed in the context of a pet's health, a primary care veterinarian consulting with a pet owner during a wellness appointment may be most persuasive to the owner for changing their pet's diet.


Comparison of 3 vancomycin dosage regimens during hemodialysis with cellulose triacetate dialyzers: post-dialysis versus intradialytic administration.
Traditionally, vancomycin is administered following dialysis to minimize drug loss when high-flux membranes are employed. Unfortunately, this approach is extremely inconvenient for patients and staff, requiring the patients to remain in the unit for at least 1 hour following dialysis. This study was designed to evaluate the feasibility of administering vancomycin during hemodialysis. Specifically, this study was designed to compare the pharmacokinetics of vancomycin when administered during the last 1-2 hours of dialysis (i.e. intra-dialytic administration) to that administered after completion of dialysis. In a randomized, 3-way crossover trial, the pharmacokinetics of vancomycin were evaluated in 9 hemodialysis patients, comparing vancomycin 15 mg/kg following dialysis (Phase I), vancomycin 15 mg/kg during the last hour of hemodialysis (Phase II) or vancomycin 30 mg/kg during the last 2 hours of hemodialysis (Phase III). Vancomycin plasma concentrations were obtained over an 8-day period and subsequent comparisons between the treatment approaches were made with paired t-tests or ANOVA, as appropriate. Dialysate vancomycin concentrations determined on Day 1 and Day 3 of Phases II and III were used to calculate the fraction of vancomycin dose removed, and were compared to plasma data using paired t-tests. Vancomycin was significantly removed (33.4 to 39.5%) during a 3- to 4-hour high-flux dialysis session occurring on Day 3 after vancomycin administration. Mean serum concentrations immediately following intradialytic vancomycin administration of 15 mg/kg over the last hour of dialysis or 30 mg/kg over the last 2 hours of dialysis were initially high (77.7 and 95.5 mcg/ml respectively), but fell to 25.9 and 40.5 mcg/ml, respectively, by 4 hours post-dialysis. Predialysis concentrations on Days 3, 5 and 8 were similar for vancomycin 30 mg/kg administered over the last 2 hours of dialysis as compared with a 15 mg/kg dose given after dialysis. Vancomycin 15 mg/kg over the last hour of dialysis resulted in significantly lower subsequent predialysis concentrations than the other dosing schemes. Vancomycin administration of 30 mg/kg over the last 2 hours of dialysis achieves serum concentrations similar to conventional dosing of 15 mg/kg after dialysis and would allow dosing on a weekly basis.


Radio-frequency catheter ablation of atypical atrioventricular nodal reentrant tachycardia from a trans-aortic approach.
Radio-frequency catheter ablation (RFCA) was introduced for the treatment of reentrant tachyarrhythmias and has proven its usefulness, efficacy, and safety. It has gained the position of an early stage treatment option rather than being a 'last resort' option for certain groups of patients with supraventricular tachycardias including atrioventricular nodal reentrant tachycardia (AVNRT). The RFCA technique for AVNRT seems to have become established throughout these years and the right-side approach is considered to be the conventional method. However, in one percent of the patients with AVNRT it has been reported that they cannot be cured by the conventional method and a left-sided approach has been recommended. We experienced a case which presented with a fast/slow atypical AVNRT. We ultimately successfully treated the case with a left-sided (trans-aortic) RFCA approach. We believe the trans-aortic RFCA approach is a necessary alternative in the case of an unsuccessful RFCA via the right-sided approach even though the frequency of its need is very low.


Analysis and visualization of Arabidopsis thaliana GWAS using web 2.0 technologies.
With large-scale genomic data becoming the norm in biological studies, the storing, integrating, viewing and searching of such data have become a major challenge. In this article, we describe the development of an Arabidopsis thaliana database that hosts the geographic information and genetic polymorphism data for over 6000 accessions and genome-wide association study (GWAS) results for 107 phenotypes representing the largest collection of Arabidopsis polymorphism data and GWAS results to date. Taking advantage of a series of the latest web 2.0 technologies, such as Ajax (Asynchronous JavaScript and XML), GWT (Google-Web-Toolkit), MVC (Model-View-Controller) web framework and Object Relationship Mapper, we have created a web-based application (web app) for the database, that offers an integrated and dynamic view of geographic information, genetic polymorphism and GWAS results. Essential search functionalities are incorporated into the web app to aid reverse genetics research. The database and its web app have proven to be a valuable resource to the Arabidopsis community. The whole framework serves as an example of how biological data, especially GWAS, can be presented and accessed through the web. In the end, we illustrate the potential to gain new insights through the web app by two examples, showcasing how it can be used to facilitate forward and reverse genetics research. Database URL: http://arabidopsis.usc.edu/


Cancer risk estimation of genotoxic chemicals based on target dose and a multiplicative model.
A mechanistic model and associated procedures are proposed for cancer risk assessment of genotoxic chemicals. As previously shown for ionizing radiation, a linear multiplicative model was found to be compatible with published experimental data for ethylene oxide, acrylamide, and butadiene. The validity of this model was anticipated in view of the multiplicative interaction of mutation with inherited and acquired growth-promoting conditions. Concurrent analysis led to rejection of an additive model (i.e. the model commonly applied for cancer risk assessment). A reanalysis of data for radiogenic cancer in mouse, dog and man shows that the relative risk coefficient is approximately the same (0.4 to 0.5 percent per rad) for tumours induced in the three species. Doses in vivo, defined as the time-integrated concentrations of ultimate mutagens, expressed in millimol x kg-1 x h (mMh) are, like radiation doses given in Gy or rad, proportional to frequencies of potentially mutagenic events. The radiation dose equivalents of chemical doses are, calculated by multiplying chemical doses (in mMh) with the relative genotoxic potencies (in rad x mMh-1) determined in vitro. In this way the relative cancer incidence increments in rats and mice exposed to ethylene oxide were shown to be about 0.4 percent per rad-equivalent, in agreement with the data for radiogenic cancer. Our analyses suggest that values of the relative risk coefficients for genotoxic chemicals are independent of species and that relative cancer risks determined in animal tests apply also to humans. If reliable animal test data are not available, cancer risks may be estimated by the relative potency. In both cases exposure dose/target dose relationships, the latter via macromolecule adducts, should be determined.