Relationship between physical activity and stiff or painful joints in mid-aged women and older women: a 3-year prospective study.
This prospective study examined the association between physical activity and the incidence of self-reported stiff or painful joints (SPJ) among mid-age women and older women over a 3-year period. Data were collected from cohorts of mid-age (48-55 years at Time 1; n = 4,780) and older women (72-79 years at Time 1; n = 3,970) who completed mailed surveys 3 years apart for the Australian Longitudinal Study on Women's Health. Physical activity was measured with the Active Australia questions and categorized based on metabolic equivalent value minutes per week: none (<40 MET x min/week); very low (40 to <300 MET x min/week); low (300 to <600 MET x min/week); moderate (600 to <1,200 MET x min/week); and high (1,200+ MET x min/week). Cohort-specific logistic regression models were used to examine the association between physical activity at Time 1 and SPJ 'sometimes or often' and separately 'often' at Time 2. Respondents reporting SPJ 'sometimes or often' at Time 1 were excluded from analysis. In univariate models, the odds of reporting SPJ 'sometimes or often' were lower for mid-age respondents reporting low (odds ratio (OR) = 0.77, 95% confidence interval (CI) = 0.63-0.94), moderate (OR = 0.82, 95% CI = 0.68-0.99), and high (OR = 0.75, 95% CI = 0.62-0.90) physical activity levels and for older respondents who were moderately (OR = 0.80, 95% CI = 0.65-0.98) or highly active (OR = 0.83, 95% CI = 0.69-0.99) than for those who were sedentary. After adjustment for confounders, these associations were no longer statistically significant. The odds of reporting SPJ 'often' were lower for mid-age respondents who were moderately active (OR = 0.71, 95% CI = 0.52-0.97) than for sedentary respondents in univariate but not adjusted models. Older women in the low (OR = 0.72, 95% CI = 0.55-0.96), moderate (OR = 0.54, 95% CI = 0.39-0.76), and high (OR = 0.61, 95% CI = 0.46-0.82) physical activity categories had lower odds of reporting SPJ 'often' at Time 2 than their sedentary counterparts, even after adjustment for confounders. These results are the first to show a dose-response relationship between physical activity and arthritis symptoms in older women. They suggest that advice for older women not currently experiencing SPJ should routinely include counseling on the importance of physical activity for preventing the onset of these symptoms.


Simulation Modeling of Cancer Clinical Trials: Application to Omitting Radiotherapy in Low-risk Breast Cancer.
We used two models to simulate a proposed noninferiority trial of radiotherapy (RT) omission in low-risk invasive breast cancer to illustrate how modeling could be used to predict the trial's outcomes, inform trial design, and contribute to practice debates. The proposed trial was a prospective randomized trial of no-RT vs RT in women age 40 to 74 years undergoing lumpectomy and endocrine therapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative, stage I breast cancer with an Oncotype DX score of 18 or lower. The primary endpoint was recurrence-free interval (RFI), including locoregional recurrence, distant recurrence, and breast cancer death. Noninferiority required the two-sided 90% confidence interval of the RFI hazard ratio (HR) for no-RT vs RT to be entirely below 1.7. Model inputs included published data. The trial was simulated 1000 times, and results were summarized as percent concluding noninferiority and mean (standard deviation) of hazard ratios for Model GE and Model M, respectively. Noninferiority was demonstrated in 18.0% and 3.7% for the two models. The respective means (SD) of the RFI hazard ratios were 1.8 (0.7) and 2.4 (0.9); most were locoregional recurrences. The mean five-year RFI rates for no-RT vs RT (SD) were 92.7% (2.9%) vs 95.5% (2.2%) and 88.4% (2.0%) vs 94.5% (1.6%). Both models showed little or no difference in breast cancer-specific or overall survival. Alternative definitions of low risk based on combinations of age and grade produced similar results. The proposed trial was unlikely to show noninferiority of omitting radiotherapy even using alternative definitions of low-risk, as the endpoint included local recurrence. Future trials regarding radiotherapy should address absolute reduction in recurrence and impact of type of recurrence on the patient.


Graphical assessment of incremental value of novel markers in prediction models: From statistical to decision analytical perspectives.
New markers may improve prediction of diagnostic and prognostic outcomes. We aimed to review options for graphical display and summary measures to assess the predictive value of markers over standard, readily available predictors. We illustrated various approaches using previously published data on 3264 participants from the Framingham Heart Study, where 183 developed coronary heart disease (10-year risk 5.6%). We considered performance measures for the incremental value of adding HDL cholesterol to a prediction model. An initial assessment may consider statistical significance (HR = 0.65, 95% confidence interval 0.53 to 0.80; likelihood ratio p < 0.001), and distributions of predicted risks (densities or box plots) with various summary measures. A range of decision thresholds is considered in predictiveness and receiver operating characteristic curves, where the area under the curve (AUC) increased from 0.762 to 0.774 by adding HDL. We can furthermore focus on reclassification of participants with and without an event in a reclassification graph, with the continuous net reclassification improvement (NRI) as a summary measure. When we focus on one particular decision threshold, the changes in sensitivity and specificity are central. We propose a net reclassification risk graph, which allows us to focus on the number of reclassified persons and their event rates. Summary measures include the binary AUC, the two-category NRI, and decision analytic variants such as the net benefit (NB). Various graphs and summary measures can be used to assess the incremental predictive value of a marker. Important insights for impact on decision making are provided by a simple graph for the net reclassification risk.


Outcomes of Adjuvant Mitotane after Resection of Adrenocortical Carcinoma: A 13-Institution Study by the US Adrenocortical Carcinoma Group.
Current treatment guidelines recommend adjuvant mitotane after resection of adrenocortical carcinoma with high-risk features (eg, tumor rupture, positive margins, positive lymph nodes, high grade, elevated mitotic index, and advanced stage). Limited data exist on the outcomes associated with these practice guidelines. Patients who underwent resection of adrenocortical carcinoma from 1993 to 2014 at the 13 academic institutions of the US Adrenocortical Carcinoma Group were included. Factors associated with mitotane administration were determined. Primary end points were recurrence-free survival (RFS) and overall survival (OS). Of 207 patients, 88 (43%) received adjuvant mitotane. Receipt of mitotane was associated with hormonal secretion (58% vs 32%; p = 0.001), advanced TNM stage (stage IV: 42% vs 23%; p = 0.021), adjuvant chemotherapy (37% vs 5%; p < 0.001), and adjuvant radiation (17% vs 5%; p = 0.01), but was not associated with tumor rupture, margin status, or N-stage. Median follow-up was 44 months. Adjuvant mitotane was associated with decreased RFS (10.0 vs 27.9 months; p = 0.007) and OS (31.7 vs 58.9 months; p = 0.006). On multivariable analysis, mitotane was not independently associated with RFS or OS, and margin status, advanced TNM stage, and receipt of chemotherapy were associated with survival. After excluding all patients who received chemotherapy, adjuvant mitotane remained associated with decreased RFS and similar OS; multivariable analyses again showed no association with recurrence or survival. Stage-specific analyses in both cohorts revealed no association between adjuvant mitotane and improved RFS or OS. When accounting for stage and adverse tumor and treatment-related factors, adjuvant mitotane after resection of adrenocortical carcinoma is not associated with improved RFS or OS. Current guidelines should be revisited and prospective trials are needed.


Confidence intervals permit, but do not guarantee, better inference than statistical significance testing.
A statistically significant result, and a non-significant result may differ little, although significance status may tempt an interpretation of difference. Two studies are reported that compared interpretation of such results presented using null hypothesis significance testing (NHST), or confidence intervals (CIs). Authors of articles published in psychology, behavioral neuroscience, and medical journals were asked, via email, to interpret two fictitious studies that found similar results, one statistically significant, and the other non-significant. Responses from 330 authors varied greatly, but interpretation was generally poor, whether results were presented as CIs or using NHST. However, when interpreting CIs respondents who mentioned NHST were 60% likely to conclude, unjustifiably, the two results conflicted, whereas those who interpreted CIs without reference to NHST were 95% likely to conclude, justifiably, the two results were consistent. Findings were generally similar for all three disciplines. An email survey of academic psychologists confirmed that CIs elicit better interpretations if NHST is not invoked. Improved statistical inference can result from encouragement of meta-analytic thinking and use of CIs but, for full benefit, such highly desirable statistical reform requires also that researchers interpret CIs without recourse to NHST.


Efficacy of Lactic Acid Bacteria (LAB) supplement in management of constipation among nursing home residents.
Constipation is a significant problem in the elderly, specifically nursing home and/or extended-care facility residents are reported to suffer from constipation. Lactic acid bacteria (LAB) are beneficial probiotic organisms that contribute to improved nutrition, microbial balance, and immuno-enhancement of the intestinal tract, as well as diarrhea and constipation effect. The objective of this study was to investigate the efficacy of this LAB supplement in the management of nursing home residents. Nineteen subjects (8M, 11F; mean age 77.1 +/- 10.1) suffering with chronic constipation were assigned to receive LAB (3.0 x 10(11) CFU/g) twice (to be taken 30 minutes after breakfast and dinner) a day for 2 weeks in November 2008. Subjects draw up a questionnaire on defecation habits (frequency of defecation, amount and state of stool), and we collected fecal samples from the subjects both before entering and after ending the trial, to investigate LAB levels and inhibition of harmful enzyme activities. Results were tested with SAS and Student's t-test. Analysis of questionnaire showed that there was an increase in the frequency of defecation and amount of stool excreted in defecation habit after LAB treatment, but there were no significant changes. And it also affects the intestinal environment, through significantly increase (p < 0.05) fecal LAB levels. In addition, tryptophanase and urease among harmful enzyme activities of intestinal microflora were significantly decreased (p < 0.05) after LAB treatment. LAB, when added to the standard treatment regimen for nursing home residents with chronic constipation, increased defecation habit such as frequency of defecation, amount and state of stool. So, it may be used as functional probiotics to improve human health by helping to prevent constipation.


Fate plasticity in the intestine: The devil is in the detail.
The intestinal epithelium possesses a remarkable ability for both proliferation and regeneration. The last two decades have generated major advances in our understanding of the stem cell populations responsible for its maintenance during homeostasis and more recently the events that occur during injury induced regeneration. These fundamental discoveries have capitalised on the use of transgenic mouse models and in vivo lineage tracing to make their conclusions. It is evident that maintenance is driven by rapidly proliferating crypt base stem cells, but complexities associated with the technicality of mouse modelling have led to several overlapping populations being held responsible for the same behaviour. Similarly, it has been shown that essentially any population in the intestinal crypt can revert to a stem cell state given the correct stimulus during epithelial regeneration. Whilst these observations are profound it is uncertain how relevant they are to human intestinal homeostasis and pathology. Here, these recent studies are presented, in context with technical considerations of the models used, to argue that their conclusions may indeed not be applicable in understanding "homeostatic regeneration" and experimental suggestions presented for validating their results in human tissue.


Treatment of maxillary sinus carcinoma: a comparison of the 1997 and 1977 American Joint Committee on cancer staging systems.
This study was conducted to assess the effectiveness of the 1997 American Joint Committee on Cancer (AJCC) staging system to predict survival and local control of patients with maxillary sinus carcinoma and to identify significant factors for overall survival, local control, and distant metastases in patients with these tumors. Ninety-seven patients with maxillary sinus carcinoma were treated with radiotherapy at Stanford University and the University of California, San Francisco between 1959-1996. The histologic type of carcinoma among the 97 patients were: 58 squamous cell carcinomas, 4 adenocarcinomas, 16 undifferentiated carcinomas, and 19 adenoid cystic carcinomas. All patients were restaged clinically according to the 1977 and 1997 AJCC staging systems. The T classification of the tumors of the patients was as follows: 8 with T2, 18 with T3, and 71 with T4 according to the 1977 system and 8 with T2, 36 with T3, and 53 with T4 according to the 1997 system. Eleven patients had lymph node involvement at diagnosis. Thirty-six patients were treated with radiotherapy alone and 61 received a combination of surgical and radiation treatments. The median follow-up for surviving patients was 78 months. The 5-year and 10-year actuarial survival rates for all patients were 34% and 31%, respectively. The 5-year survival estimate by the 1977 AJCC system (P = 0.06) was 75% for Stage II, 19% for Stage III, and 34% for Stage IV and by the 1997 AJCC system (P = 0.006) was 75% for Stage II, 37% for Stage III, and 28% for Stage IV. Significant prognostic factors for survival by multivariate analysis included age (favoring younger age, P<0.001), 1997 T classification (favoring T2-3, P = 0. 001), lymph node involvement at diagnosis (favoring N0, P = 0.002), treatment modality of the primary tumor site (favoring surgery and radiotherapy, P = 0.009), and gender (favoring female patients, P = 0.04). The overall radiation time was of borderline significance (favoring shorter time, P = 0.06). The actuarial 5-year local control rate was 43%. By the 1977 AJCC system (P = 0.78) it was 62% with T2, 36% with T3, and 45% with T4 and using the 1997 AJCC system (P = 0.29) it was 62% with T2, 53% with T3, and 36% with T4. The only significant prognostic factor for local control for all patients by multivariate analysis was local therapy, favoring surgery and radiotherapy over radiotherapy alone (P< 0.001). For patients treated with surgery, pathologic margin status correlated with local control (P = 0.007) and for patients treated with radiation alone, higher tumor dose (P = 0.007) and shorter overall treatment time (P = 0.04) were associated with fewer local recurrences. The 5-year estimate of freedom from distant metastases was 66%. The 1997 T classification, N classification, and lymph node recurrence were adverse prognostic factors for distant metastases on multivariate analysis. There were 22 complications in 16 patients, representing a 30% actuarial risk of developing late complications at 10 years. The 1997 AJCC staging system was found to be superior to the 1977 AJCC staging system in predicting both survival and local control in this patient population. Combined surgical and radiation treatment to the primary tumor yielded higher survival and local control than radiotherapy alone. Other significant prognostic factors for survival were patient age, gender, and lymph node (N) classification. Prolonged overall radiation time was associated with poorer survival and local control. Late severe toxicity from the treatment of these tumors was a significant problem in long term survivors. Improved radiotherapy techniques should lead to decreased injury to the surrounding normal tissues. (c) 1999 American Cancer Society.


Hemispheric asymmetry: contributions from brain imaging.
A series of studies using functional and structural magnetic resonance imaging, including diffusion tensor imaging measures also, to elucidate the aspects of hemispheric asymmetry are reviewed. It is suggested that laterality evolved as a response to the demands of language and the need for air-based communication which may have necessitated a division of labor between the hemispheres in order to avoid having duplicate copies in both the hemispheres that would increase processing redundancy. This would have put pressure on brain structures related to the evolution of language and speech, such as the left peri-Sylvian region. MRI data are provided showing structural and functional asymmetry in this region of the brain and how fibers connecting the right and left peri-Sylvian regions pass through the corpus callosum. It is further suggested that the so-called Yakelovian-torque, i.e., the twisting of the brain along the longitudinal axis, with the right frontal and left occipital poles protruding beyond the corresponding left and right sides, was necessary for the expansion of the left peri-Sylvian region and the right occipito-parietal regions subserving the processing of spatial relations. Functional magnetic resonance imaging data related to sex differences for visuo-spatial processing are presented showing enhanced right-sided activation in posterior parts of the brain in both sexes, and frontal activation including Broca's area in the female group only, suggesting that males and females use different strategies when solving a cognitive task. The paper ends with a discussion of the role of the corpus callosum in laterality and the role played by structural asymmetry in understanding corresponding functional asymmetry. WIREs Cogni Sci 2011 2 461-478 DOI: 10.1002/wcs.122 For further resources related to this article, please visit the WIREs website.


"This is the medicine:" A Kenyan community responds to a sexual concurrency reduction intervention.
We report the results of the first study designed to evaluate the feasibility and acceptability of an HIV prevention intervention focused on concurrent sexual partnerships. Mathematical models and longitudinal studies of stable couples indicate concurrency plays a critical role in sustaining generalized HIV epidemics in heterosexual populations, and East and Southern African nations identified concurrency reduction as a priority for HIV prevention. "Know Your Network" (KYN) is a single-session community-level concurrency awareness intervention designed to address this need. It is rooted in traditional social network research, but takes advantage of new network methodology and years of participatory action research with communities living in a region of Kenya with the highest HIV prevalence nationally. KYN combines didactic presentation, interactive exercises, high-impact graphics, and a network survey with immediate visualization of the results, to prompt a community conversation about sexual norms. We combined focus group discussions and the traditional east African baraza to evaluate the feasibility and acceptability of KYN for use with adults living in rural Nyanza Province, Kenya. We were able to implement KYN with fidelity to its components. Participants understood the intervention's messages about concurrency and its role in HIV transmission through sexual networks. They agreed to provide anonymous egocentric data on their sexual partnerships, and in return we successfully simulated a representation of their local network for them to view and discuss. This launched a dynamic conversation about concurrency and sexual norms that persisted after the intervention. The concurrency message was novel, but resonant to participants, who reported sharing it with their children, friends, and sexual partners. With clear evidence of KYN's feasibility and acceptability, it would be appropriate to evaluate the effectiveness of the intervention using a community-randomized trial. If effective, KYN would offer an inexpensive complement to ongoing comprehensive HIV prevention efforts in generalized epidemic settings.


Methodology developed to make the Quebec indoor radon potential map.
This paper presents a relevant approach to predict the indoor radon potential based on the combination of the radiogeochemical data and the indoor radon measurements in the Quebec province territory (Canada). The Quebec ministry of health asked for such a map to identify the radon-prone areas to manage the risk for the population related to indoor radon exposure. Three radiogeochemical criteria including (1) equivalent uranium (eU) concentration from airborne surface gamma-ray surveys, (2) uranium concentration measurements in sediments, (3) bedrock and surficial geology were combined with 3082 basement radon concentration measurements to identify the radon-prone areas. It was shown that it is possible to determine thresholds for the three criteria that implied statistically significant different levels of radon potential using Kruskal-Wallis one way analyses of variance by ranks. The three discretized radiogeochemical datasets were combined into a total predicted radon potential that sampled 98% of the studied area. The combination process was also based on Kruskal-Wallis one way ANOVA. Four statistically significant different predicted radon potential levels were created: low, medium, high and very high. Respectively 10 and 13% of the dwellings exceed the Canadian radon guideline of 200 Bq/m(3) in low and medium predicted radon potentials. These proportions rise up to 22 and 45% respectively for high and very high predicted radon potentials. This predictive map of indoor radon potential based on the radiogeochemical data was validated using a map of confirmed radon exposure in homes based on the basement radon measurements. It was shown that the map of predicted radon potential based on the radiogeochemical data was reliable to identify radon-prone areas even in zones where no indoor radon measurement exists.


Pneumonia research to reduce childhood mortality in the developing world.
Pneumonia is an illness, usually caused by infection, in which the lungs become inflamed and congested, reducing oxygen exchange and leading to cough and breathlessness. It affects individuals of all ages but occurs most frequently in children and the elderly. Among children, pneumonia is the most common cause of death worldwide. Historically, in developed countries, deaths from pneumonia have been reduced by improvements in living conditions, air quality, and nutrition. In the developing world today, many deaths from pneumonia are also preventable by immunization or access to simple, effective treatments. However, as we highlight here, there are critical gaps in our understanding of the epidemiology, etiology, and pathophysiology of pneumonia that, if filled, could accelerate the control of pneumonia and reduce early childhood mortality.


First-person body view modulates the neural substrates of episodic memory and autonoetic consciousness: A functional connectivity study.
Episodic memory (EM) is classically conceived as a memory for events, localized in space and time, and characterized by autonoetic consciousness (ANC) allowing to mentally travel back in time and subjectively relive an event. Building on recent evidence that the first-person visual co-perception of one's own body during encoding impacts EM, we used a scene recognition task in immersive virtual reality (VR) and measured how first-person body view would modulate peri-encoding resting-state fMRI, EM performance, and ANC. Specifically, we investigated the impact of body view on post-encoding functional connectivity in an a priori network of regions related either to EM or multisensory bodily processing and used these regions in a seed-to-whole brain analysis. Post-encoding connectivity between right hippocampus (rHC) and right parahippocampus (rPHC) was enhanced when participants encoded scenes while seeing their body. Moreover, the strength of connectivity between the rHC, rPHC and the neocortex displayed two main patterns with respect to body view. The connectivity with a sensorimotor fronto-parietal network, comprising primary somatosensory and primary motor cortices, correlated with ANC after - but not before - encoding, depending on body view. The opposite change of connectivity was found between rHC, rPHC and the medial parietal cortex (from being correlated with ANC before encoding to an absence of correlation after encoding), but irrespective of body view. Linking immersive VR and fMRI for the study of EM and ANC, these findings suggest that seeing one's own body during encoding impacts the brain activity related to EM formation by modulating the connectivity between the right hippocampal formation and the neocortical regions involved in the processing of multisensory bodily signals and self-consciousness.


Outcomes of acute and chronic patients with magnetic resonance imaging-confirmed symptomatic lumbar disc herniations receiving high-velocity, low-amplitude, spinal manipulative therapy: a prospective observational cohort study with one-year follow-up.
The purposes of this study were to evaluate patients with low-back pain (LBP) and leg pain due to magnetic resonance imaging-confirmed disc herniation who are treated with high-velocity, low-amplitude spinal manipulation in terms of their short-, medium-, and long-term outcomes of self-reported global impression of change and pain levels at various time points up to 1 year and to determine if outcomes differ between acute and chronic patients using a prospective, cohort design. This prospective cohort outcomes study includes 148 patients (between ages of 18 and 65 years) with LBP, leg pain, and physical examination abnormalities with concordant lumbar disc herniations. Baseline numerical rating scale (NRS) data for LBP, leg pain, and the Oswestry questionnaire were obtained. The specific lumbar spinal manipulation was dependent upon whether the disc herniation was intraforaminal or paramedian as seen on the magnetic resonance images and was performed by a doctor of chiropractic. Outcomes included the patient's global impression of change scale for overall improvement, the NRS for LBP, leg pain, and the Oswestry questionnaire at 2 weeks, 1, 3, and 6 months, and 1 year after the first treatment. The proportion of patients reporting "improvement" on the patient's global impression of change scale was calculated for all patients and acute vs chronic patients. Pretreatment and posttreatment NRS scores were compared using the paired t test. Baseline and follow-up Oswestry scores were compared using the Wilcoxon test. Numerical rating scale and Oswestry scores for acute vs chronic patients were compared using the unpaired t test for NRS scores and the Mann-Whitney U test for Oswestry scores. Logistic regression analysis compared baseline variables with "improvement." Significant improvement for all outcomes at all time points was reported (P < .0001). At 3 months, 90.5% of patients were "improved" with 88.0% "improved" at 1 year. Although acute patients improved faster by 3 months, 81.8% of chronic patients reported "improvement" with 89.2% "improved" at 1 year. There were no adverse events reported. A large percentage of acute and importantly chronic lumbar disc herniation patients treated with chiropractic spinal manipulation reported clinically relevant improvement.


Dental utilization by children in Hispanic agricultural worker families in California.
Agricultural worker families encounter multiple barriers to accessing all needed dental care. This study investigated predisposing, enabling, and need factors associated with children's past year dental utilization among Hispanic agricultural worker families in central California. Oral health survey and clinical data were collected from families participating in a larger, population-based study in 2006-7. Generalized estimating equation logit regression assessed effects on a dental visit among children aged 0-17 (n=405). Analyses adjusted for clustering of children in the same household. Predisposing (sociodemographics), enabling (child's dental insurance, usual source of dental care, caregiver past year dental visit, acculturation level, income and education), and need (caregiver's oral health rating, perception of cavities, and clinically-determined treatment urgency) factors were examined. Half (51%) the children had a past year dental visit, while 23% had never been to a dentist. In the final model, children were less likely to have a past year dental visit if they were foreign-born, male, had caregivers that thought they had cavities or were unsure, and if the dentist recommended treatment 'at earliest convenience'. Children aged 6-12, with a regular dental care source, and whose caregivers had a recent dentist visit were more likely to have a past year dental visit. Children were more likely to have a past year dental visit if they had a usual source of dental care (OR =4.78, CI=2.51-9.08), and if the caregiver had a past year dental visit (OR=1.88, CI=1.04-3.38). Emphasis should be placed on these two modifiable factors to increase children's dental utilization.


Structural and functional characterization of the actin-1 gene promoter from the Antheraea pernyi (Lepidoptera: Saturniidae).
The Chinese oak silkworm, Antheraea pernyi, is an economically important insect of the Saturniidae family. In this study, genome walking was performed to obtain an A. pernyi actin promoter, which can be employed in transgenic or stable cell line expression systems. The putative promoter was analyzed by the online promoter analysis programs at the Berkeley Drosophila Genome Project and the Web Promoter Scan Service, which led to the recognition of several functional elements. With respect to these elements, a series of actin A1 promoter fragments with 5'-deletions were generated that were then used to construct different vectors expressing Green Fluorescent Protein (GFP). The plasmids were transfected into Sf9 cells and GFP expression was determined by observing GFP fluorescence in cells and by measuring GFP mRNA levels with real-time polymerase chain reaction. Sequence comparisons indicated that the sequence cloned from A. pernyi was the actin A1 promoter. The basic function of the promoter was verified by constructing expression vectors and observing GFP expression. In addition, real-time polymerase chain reaction revealed a strong inhibitory element may exist upstream of the TATA box, which downregulated gene expression. The actin A1 promoter is an ideal candidate for use in A. pernyi transgenic systems.


The Impact of Surgical Amputation and Valproic Acid on Pain and Functional Trajectory: Results from the Veterans Integrated Pain Evaluation Research (VIPER) Randomized, Double-Blinded Placebo-Controlled Trial.
To determine if the perioperative administration of valproic acid reduces the incidence of chronic pain three months after amputation or revision surgery. Multicenter, randomized, double-blind, placebo-controlled trial. Academic, military, and veteran medical centers. One hundred twenty-eight patients undergoing amputation or amputation revision surgery at Duke University Hospital, Walter Reed National Military Medical Center, or the Durham Veterans Affairs Medical Center for either medical disease or trauma. Patients were randomized to placebo or valproic acid for the duration of hospitalization and treated with multimodal analgesic care, including regional anesthetic blockade. Primary outcome was the proportion of patients with chronic pain at three months (average numeric pain score intensity of 3/10 or greater). Secondary outcomes included functional trajectories (assessed with the Brief Pain Inventory short form and the Defense and Veterans Pain Rating Scale). The overall rate of chronic pain was 68.2% in the 107 patients who completed the end point assessment. There was no significant effect of perioperative valproic acid administration, with a rate of 65.45% (N = 36) in the treatment group and a rate of 71.15% (N = 37) in the placebo group. Overall, pain scores decreased from baseline to follow-up (median = -2 on the numeric pain scale). Patients additionally experienced improvements in self-perceived function. The rate of chronic pain after amputation surgery is not significantly improved with the perioperative administration of valproic acid. In this cohort treated with multimodal perioperative analgesia and regional anesthetic blockade, we observed improvements in both pain severity and function.


Recognition memory for 2,578 monosyllabic words.
In two studies, participants studied 30 lists of 50 words and were tested on 30 lists of 100 words. Item-level multiple regression analyses were conducted on hits, false alarms, hits minus false alarms, d', and C. The predictor variables were objective frequency, subjective frequency, imageability, orthographic similarity, phonological similarity, phonological-to-orthographic N (PON), age of acquisition (AoA), and word length. The regression equations accounted for 45.9% of the variance in hit rates, 14.9% of the variance in false alarm rates, and 29.2% of the variance in hits minus false alarms. Other noteworthy results were that: (a) hit rates positively correlated with false alarms, (b) objective frequency negatively correlated with both hit rates and false alarm rates, (c) AoA positively correlated with hit rates and negatively correlated with false alarm rates, (d) length negatively correlated with hit rates and positively correlated with false alarm rates, (e) orthographic uniqueness was positively correlated with hit rates and negatively correlated with false alarms, (f) PON positively correlated with false alarm rates, (g) imageability produced the typical mirror pattern, and (h) imageability and length were the strongest predictors of performance. Results were largely compatible with predictions made by single- and dual-process theories of recognition memory.


Protective Effect of Amyloid-β Peptides Against Herpes Simplex Virus-1 Infection in a Neuronal Cell Culture Model.
Senile amyloid plaques are one of the main hallmarks of Alzheimer's disease (AD). They correspond to insoluble deposits of amyloid-β peptides (Aβ) and are responsible for the inflammatory response and neurodegeneration that lead to loss of memory. Recent data suggest that Aβ possess antimicrobial and anti-viral activity in vitro. Here, we have used cocultures of neuroglioma (H4) and glioblastoma (U118-MG) cells as a minimal in vitro model to investigate whether Aβ is produced by neuroglioma cells and whether this could result in protective anti-viral activity against HSV-1 infection. Results showed that H4 cells secreted Aβ42 in response to HSV-1 challenge and that U118-MG cells could rapidly internalize Aβ42. Production of pro-inflammatory cytokines TNFα and IL-1β by H4 and U118-MG cells occurred under basal conditions but infection of the cells with HSV-1 did not significantly upregulate production. Both cell lines produced low levels of IFNα. However, extraneous Aβ42 induced strong production of these cytokines. A combination of Aβ42 and HSV-1 induced production of pro-inflammatory cytokines TNFα and IL-1β, and IFNα in the cell lines. The reported anti-viral protection of Aβ42 was revealed in transfer experiments involving conditioned medium (CM) of HSV-1-infected H4 cells. CM conferred Aβ-dependent protection against HSV-1 replication in de novo cultures of H4 cells challenged with HSV-1. Type 1 interferons did not play a role in these assays. Our data established that H4 neuroglioma cells produced Aβ42 in response to HSV-1 infection thus inhibiting secondary replication. This mechanism may play a role in the etiology of AD.


Impact of prior exercise on hamstring flexibility: a comparison of proprioceptive neuromuscular facilitation and static stretching.
Position stands from the American College of Sports Medicine and the Surgeon General site a need for strategies capable of enhancing the effectiveness of stretching on flexibility and joint range of motion. One strategy for enhancing flexibility that has received anecdotal support but lacks substantial experimental evidence is the impact of prior exercise. This study compared 5 minutes of static stretching and proprioceptive neuromuscular facilitation (PNF) on hamstring flexibility performed with and without exercise. Forty undergraduate student-athletes participated in a repeated measure, counterbalanced experimental design. Within-group comparisons indicated that PNF resulted in a significant (p < 0.05) increase in flexibility after 60 minutes of exercise when compared with baseline (9.6%) and without exercise (7.8%). No differences were observed with static stretching across time. In addition, no differences were observed between the groups at any time point. Results demonstrated that PNF performed after exercise enhanced acute hamstring flexibility, and implementing a PNF stretching routine following exercise may augment current stretching practices among athletes.


Occurrence of Poecilochirus austroasiaticus (Acari: Parasitidae) in forensic autopsies and its application on postmortem interval estimation.
Despite the fact that mites were used at the dawn of forensic entomology to elucidate the postmortem interval, their use in current cases remains quite low for procedural reasons such as inadequate taxonomic knowledge. A special interest is focused on the phoretic stages of some mite species, because the phoront-host specificity allows us to deduce in many occasions the presence of the carrier (usually Diptera or Coleoptera) although it has not been seen in the sampling performed in situ or in the autopsy room. In this article, we describe two cases where Poecilochirus austroasiaticus Vitzthum (Acari: Parasitidae) was sampled in the autopsy room. In the first case, we could sample the host, Thanatophilus ruficornis (Küster) (Coleoptera: Silphidae), which was still carrying phoretic stages of the mite on the body. That attachment allowed, by observing starvation/feeding periods as a function of the digestive tract filling, the establishment of chronological cycles of phoretic behavior, showing maximum peaks of phoronts during arrival and departure from the corpse and the lowest values in the phase of host feeding. From the sarcosaprophagous fauna, we were able to determine in this case a minimum postmortem interval of 10 days. In the second case, we found no Silphidae at the place where the corpse was found or at the autopsy, but a postmortem interval of 13 days could be established by the high specificity of this interspecific relationship and the departure from the corpse of this family of Coleoptera.


Epigenetic regulation of the tumor suppressor gene TCF21 on 6q23-q24 in lung and head and neck cancer.
The identification of tumor suppressor genes has classically depended on their localization within recurrent regions of loss of heterozygosity. According to Knudson's two-hit hypothesis, the remaining allele is lost, either genetically or, more recently identified, through epigenetic events. To date, retrospective analyses have determined promoter methylation as a common alternative alteration in cancer cells to silence cancer-related genes. Here we report an application of restriction landmark genomic scanning that allows for DNA methylation profiling along a region of recurrent loss of heterozygosity at chromosome 6q23-q24. This approach resulted in the identification of a tumor suppressor gene, TCF21, which is frequently lost in human malignancies. We demonstrate that TCF21 is expressed in normal lung airway epithelial cells and aberrantly methylated and silenced in the majority of head and neck squamous cell carcinomas and non-small-cell lung cancers analyzed. TCF21 is known to regulate mesenchymal cell transition into epithelial cells, a property that has been shown to be deficient in carcinomas. We further demonstrate that exogenous expression of TCF21 in cells that have silenced the endogenous TCF21 locus resulted in a reduction of tumor properties in vitro and in vivo.


Identification of carbohydrate anomers using ion mobility-mass spectrometry.
Carbohydrates are ubiquitous biological polymers that are important in a broad range of biological processes. However, owing to their branched structures and the presence of stereogenic centres at each glycosidic linkage between monomers, carbohydrates are harder to characterize than are peptides and oligonucleotides. Methods such as nuclear magnetic resonance spectroscopy can be used to characterize glycosidic linkages, but this technique requires milligram amounts of material and cannot detect small amounts of coexisting isomers. Mass spectrometry, on the other hand, can provide information on carbohydrate composition and connectivity for even small amounts of sample, but it cannot be used to distinguish between stereoisomers. Here, we demonstrate that ion mobility-mass spectrometry--a method that separates molecules according to their mass, charge, size, and shape--can unambiguously identify carbohydrate linkage-isomers and stereoisomers. We analysed six synthetic carbohydrate isomers that differ in composition, connectivity, or configuration. Our data show that coexisting carbohydrate isomers can be identified, and relative concentrations of the minor isomer as low as 0.1 per cent can be detected. In addition, the analysis is rapid, and requires no derivatization and only small amounts of sample. These results indicate that ion mobility-mass spectrometry is an effective tool for the analysis of complex carbohydrates. This method could have an impact on the field of carbohydrate synthesis similar to that of the advent of high-performance liquid chromatography on the field of peptide assembly in the late 1970s.


Assessing statistical competencies in clinical and translational science education: one size does not fit all.
Statistics is an essential training component for a career in clinical and translational science (CTS). Given the increasing complexity of statistics, learners may have difficulty selecting appropriate courses. Our question was: what depth of statistical knowledge do different CTS learners require? For three types of CTS learners (principal investigator, co-investigator, informed reader of the literature), each with different backgrounds in research (no previous research experience, reader of the research literature, previous research experience), 18 experts in biostatistics, epidemiology, and research design proposed levels for 21 statistical competencies. Statistical competencies were categorized as fundamental, intermediate, or specialized. CTS learners who intend to become independent principal investigators require more specialized training, while those intending to become informed consumers of the medical literature require more fundamental education. For most competencies, less training was proposed for those with more research background. When selecting statistical coursework, the learner's research background and career goal should guide the decision. Some statistical competencies are considered to be more important than others. Baseline knowledge assessments may help learners identify appropriate coursework. Rather than one size fits all, tailoring education to baseline knowledge, learner background, and future goals increases learning potential while minimizing classroom time.


How often does alpha-methylacyl-CoA-racemase contribute to resolving an atypical diagnosis on prostate needle biopsy beyond that provided by basal cell markers?
Alpha-methylacyl-CoA-racemase (AMACR), a recently discovered tumor marker for prostate cancer, is being used increasingly in conjunction with hematoxylin and eosin (H&E) histology and basal cell markers in the workup of difficult prostate needle biopsies. However, it is not known how often a positive AMACR staining is used merely to support a malignant diagnosis that could otherwise be established based on routine H&E histology and negative basal cell staining. This study included 307 prostate needle biopsies that were sent to us for consultation diagnosed as "atypical" by contributing pathologists. Immunohistochemistry for AMACR, high molecular weight cytokeratin, and p63 was performed. AMACR staining intensity was graded as negative, weak, moderate, and strong. Only staining that was significantly stronger than that of background benign glands was considered positive. An "expert review" diagnosis was first rendered as benign, atypical, or cancer based on the H&E-stained section and basal cell marker stains without the knowledge of AMACR expression. The AMACR stains were then reviewed and a final diagnosis was rendered. A total of 215 cases had a final diagnosis of cancer following evaluation of the H&E-stained section, basal cell markers, and AMACR. Of these 215 cases, 176 (81.9%) were positive and 39 (18.1%) were negative for AMACR staining. Of 81 cases with a final diagnosis of atypical following review of all material, 42 (51.9%) were positive and 39 (48.1%) were negative for AMACR staining. When AMACR staining was negative, in no case was the initial cancer, atypical, or benign diagnosis (based on routine histology and negative basal cell markers) changed based on AMACR stain results. Of 115 cases called atypical after expert review, 76 were positive for AMACR; of these 76 cases, 34 (44.7%) were changed to a final diagnosis of cancer. AMACR expression was positive, with moderate and strong staining in 30 of the 34 cases (88.2%), for which the immunohistochemical result converted the expert review atypical diagnosis to a final cancer diagnosis. Of these 34 cases, 11 underwent radical prostatectomy, and cancer was found in all cases. Three additional patients underwent repeat biopsy, and cancer was present in the repeat biopsy in 2 patients. The cases whose diagnosis was changed from "atypical" on expert review to cancer were all highly suspicious for cancer based on H&E histology and negative basal cell markers, yet a definitive cancer diagnosis could not be established because of small size, insufficient cytologic atypia, or biopsy artifact. Interpretation and use of AMACR staining should be executed with caution. A negative AMACR stain can be seen in approximately 18% of cases considered to be cancer based on H&E stain combined with negative basal cell markers. A positive AMACR staining converted an atypical diagnosis, based on suspicious histology and negative basal cell marker stains, to cancer in approximately 10% (34 of 307) of cases thought to be atypical by contributing pathologists and in approximately 50% (34 of 76) of cases thought be atypical on expert review by a specialist in genitourinary pathology.


Evaluation of the persistence of transformation products from ozonation of trace organic compounds - a critical review.
Ozonation is an efficient treatment system to reduce the concentration of trace organic compounds (TrOCs) from technical aquatic systems such as drinking water, wastewater and industrial water, etc. Although it is well established that ozonation generally improves the removal of organic matter in biological post-treatment, little is known about the biodegradability of individual transformation products resulting from ozonation of TrOCs. This publication provides a qualified assessment of the persistence of ozone-induced transformation products based on a review of published product studies and an evaluation of the biodegradability of transformation products with the biodegradability probability program (BIOWIN) and the University of Minnesota Pathway Prediction System (UM-PPS). The oxidation of TrOCs containing the four major ozone-reactive sites (olefins, amines, aromatics and sulfur-containing compounds) follows well described reaction pathways leading to characteristic transformation products. Assessment of biodegradability revealed a high sensitivity to the formed products and hence the ozone-reactive site present in the target compound. Based on BIOWIN, efficient removal can be expected for products from cleavage of olefin groups and aromatic rings. In contrast, estimations and literature indicate that hydroxylamines and N-oxides, the major products from ozonation of secondary and tertiary amines are not necessarily better removed in biological post-treatment. According to UM-PPS, degradation of these products might even occur via reformation of the corresponding amine. Some product studies with sulfide-containing TrOCs showed a stoichiometric formation of sulfoxides from oxygen transfer reactions. However, conclusions on the fate of transformation products in biological post-treatment cannot be drawn based on BIOWIN and UM-PPS.


Intraoperative hyperspectral label-free imaging: from system design to first-in-patient translation.
Despite advances in intraoperative surgical imaging, reliable discrimination of critical tissue during surgery remains challenging. As a result, decisions with potentially life-changing consequences for patients are still based on the surgeon's subjective visual assessment. Hyperspectral imaging (HSI) provides a promising solution for objective intraoperative tissue characterisation, with the advantages of being non-contact, non-ionising and non-invasive. However, while its potential to aid surgical decision-making has been investigated for a range of applications, to date no real-time intraoperative HSI (iHSI) system has been presented that follows critical design considerations to ensure a satisfactory integration into the surgical workflow. By establishing functional and technical requirements of an intraoperative system for surgery, we present an iHSI system design that allows for real-time wide-field HSI and responsive surgical guidance in a highly constrained operating theatre. Two systems exploiting state-of-the-art industrial HSI cameras, respectively using linescan and snapshot imaging technology, were designed and investigated by performing assessments against established design criteria and ex vivo tissue experiments. Finally, we report the use of our real-time iHSI system in a clinical feasibility case study as part of a spinal fusion surgery. Our results demonstrate seamless integration into existing surgical workflows.


Genetic and environmental factors shape the host response to Helicobacter hepaticus: insights into IBD pathogenesis.
Pathobionts are members of the gut microbiota with the capacity to cause disease when there is malfunctioning intestinal homeostasis. These organisms are thought to be major contributors to the pathogenesis of inflammatory bowel disease (IBD), a group of chronic inflammatory disorders driven by dysregulated responses towards the microbiota. Over two decades have passed since the discovery of Helicobacter hepaticus, a mouse pathobiont which causes colitis in the context of immune deficiency. During this time, we have developed a detailed understanding of the cellular players and cytokine networks which drive H. hepaticus immunopathology. However, we are just beginning to understand the microbial factors that enable H. hepaticus to interact with the host and influence colonic health and disease. Here we review key H. hepaticus-host interactions, their relevance to other exemplar pathobionts and how when maladapted they drive colitis. Further understanding of these pathways may offer new therapeutic approaches for IBD.


All-optical half adder using cross gain modulation in semiconductor optical amplifiers.
By using the gain nonlinearity characteristics of semiconductor optical amplifier, an all-optical binary half adder at 10 Gbps is demonstrated. The half adder operates in a single mechanism, which is cross gain modulation. The half adder utilizes two logic functions of SUM and CARRY, which can be demonstrated by using XOR and AND gates, respectively. The extinction ratios of both XOR and AND gates are about 6.1 dB. By achieving this experiment, we also explored the possibilities for the enhanced complex logic operation and higher chances for multiple logic integration.


Methylation Tolerance-Based Functional Assay to Assess Variants of Unknown Significance in the MLH1 and MSH2 Genes and Identify Patients With Lynch Syndrome.
Approximately 75% of patients with suspected Lynch syndrome carry variants in MLH1 or MSH2, proteins encoded by these genes are required for DNA mismatch repair (MMR). However, 30% of these are variants of unknown significance (VUS). A assay that measures cell response to the cytotoxic effects of a methylating agent can determine the effects of VUS in MMR genes and identify patients with constitutional MMR-deficiency syndrome. We adapted this method to test the effects of VUS in MLH1 and MSH2 genes found in patients with suspected Lynch syndrome. We transiently expressed MLH1 or MSH2 variants in MLH1- or MSH2-null human colorectal cancer cell lines (HCT116 or LoVo), respectively. The MMR process causes death of cells with methylation-damaged DNA bases, so we measured proportions of cells that undergo death following exposure to the methylating agent; cells that escaped its toxicity were considered to have variants that affect function of the gene product. Using this assay, we analyzed 88 variants (mainly missense variants), comprising a validation set of 40 previously classified variants (19 in MLH1 and 21 in MSH2) and a prospective set of 48 VUS (25 in MLH1 and 23 in MSH2). Prediction scores were calculated for all VUS according to the recommendations of the American College of Medical Genetics and Genomics, based on clinical, somatic, in silico, population, and functional data. The assay correctly classified 39 of 40 variants in the validation set. The assay identified 12 VUS that did alter function of the gene product and 28 VUS that did not; the remaining 8 VUS had intermediate effects on MMR capacity and could not be classified. Comparison of assay results with prediction scores confirmed the ability of the assay to discriminate VUS that affected the function of the gene products from those that did not. Using an assay that measures the ability of the cells to undergo death following DNA damage induction by a methylating agent, we were able to assess whether variants in MLH1 and MSH2 cause defects in DNA MMR. This assay might be used to help assessing the pathogenicity of VUS in MLH1 and MSH2 found in patients with suspected Lynch syndrome.


Social participation and coronary heart disease risk in a large prospective study of UK women.
Participation in social activities is thought to prevent heart disease, but evidence is inconclusive. We assessed whether participating in social activities reduces the risk of coronary heart disease (CHD) in a large prospective study of 735,159 middle-aged UK women. Women reported their participation in eight social activities (religious group, voluntary work, adult education, art/craft/music, dancing, sports club, yoga, bingo) and were followed for first CHD event (hospital admission or death) over the next 8.6 years. Cox regression models were used to estimate relative risks for CHD incidence by participation in each and in any of the social activities. After adjustment for age and region only, every activity except bingo was associated with a reduced risk of CHD (n = 30,756 cases in total). However, after additional adjustment for 11 factors (deprivation, education, smoking, physical activity, body mass index, alcohol, marital status, self-rated health, happiness, hypertension, diabetes), every relative risk estimate moved close to 1.0. For example, for participation in any of the activities compared with none, the relative risk adjusted for age and region only was 0.83 (99% confidence interval 0.81-0.86), but changed to 1.06 (99% confidence interval 1.02-1.09) after additional adjustment. Adjustment for education, self-rated health, smoking and physical activity attenuated the associations most strongly. Residual confounding and other unmeasured factors may well account for any small remaining associations. Associations between participation in various social activities and CHD risk appear to be largely or wholly due to confounding by personal characteristics of the participants.


Tgfb1 expressed in the Tgfb3 locus partially rescues the cleft palate phenotype of Tgfb3 null mutants.
Although TGF-beta isoforms (TGF-beta1-3) display very similar biochemical characteristics in vitro, it has been determined that they demonstrate different or even opposing effects in vivo. During embryogenesis, TGF-betas play important roles in several developmental processes. Tgfb3 is strongly expressed in the prefusion palatal epithelium, and mice lacking Tgfb3 display a cleft of the secondary palate. To test whether the effect of TGF-beta3 in palatogenesis is isoform-specific in vivo, we generated a knockin mouse by replacing the coding region of exon1 in the Tgfb3 gene with the full-length Tgfb1 cDNA, which resulted in the expression of Tgfb1 in the Tgfb3 expressing domain. The homozygote knockin mice display a complete fusion at the mid-portion of the secondary palate, while the most anterior and posterior regions fail to fuse appropriately indicating that in vivo replacement of TGF-beta3 with TGF-beta1 can only partially correct the epithelial fusion defect of Tgfb3 knockout embryos. Palatal shelves of Tgfb1 knockin homozygote mice adhere, intercalate, and form characteristic epithelial triangles. However, decreased apoptosis in the midline epithelium, slower breakdown of the basement membrane and a general delay in epithelial fusion were observed when compared to control littermates. These results demonstrate an isoform-specific role for TGF-beta3 in the palatal epithelium during palate formation, which cannot be fully substituted with TGF-beta1.


A two-qubit molecular architecture for electron-mediated nuclear quantum simulation.
A switchable interaction between pairs of highly coherent qubits is a crucial ingredient for the physical realization of quantum information processing. One promising route to enable quantum logic operations involves the use of nuclear spins as protected elementary units of information, qubits. Here we propose a simple way to use fast electronic spin excitations to switch the effective interaction between nuclear spin qubits and the realization of a two-qubit molecular architecture based on highly coherent vanadyl moieties to implement quantum logic operations. Controlled generation of entanglement between qubits is possible here through chemically tuned magnetic coupling between electronic spins, which is clearly evidenced by the splitting of the vanadium(iv) hyperfine lines in the continuous-wave electron paramagnetic resonance spectrum. The system has been further characterized by pulsed electron paramagnetic resonance spectroscopy, evidencing remarkably long coherence times. The experimentally derived spin Hamiltonian parameters have been used to simulate the system dynamics under the sequence of pulses required to implement quantum gates in a realistic description that includes also the harmful effect of decoherence. This demonstrates the possibility of using this molecular complex to implement a control-Z (CZ) gate and simple quantum simulations. Indeed, we also propose a proof-of-principle experiment based on the simulation of the quantum tunneling of the magnetization in a S = 1 spin system.


Evolution and population structure of Salmonella enterica serovar Newport.
Salmonellosis caused by Salmonella enterica serovar Newport is a major global public health concern, particularly because S. Newport isolates that are resistant to multiple drugs (MDR), including third-generation cephalosporins (MDR-AmpC phenotype), have been commonly isolated from food animals. We analyzed 384 S. Newport isolates from various sources by a multilocus sequence typing (MLST) scheme to study the evolution and population structure of the serovar. These were compared to the population structure of S. enterica serovars Enteritidis, Kentucky, Paratyphi B, and Typhimurium. Our S. Newport collection fell into three lineages, Newport-I, Newport-II, and Newport-III, each of which contained multiple sequence types (STs). Newport-I has only a few STs, unlike Newport-II or Newport-III, and has possibly emerged recently. Newport-I is more prevalent among humans in Europe than in North America, whereas Newport-II is preferentially associated with animals. Two STs of Newport-II encompassed all MDR-AmpC isolates, suggesting recent global spread after the acquisition of the bla(CMY-2) gene. In contrast, most Newport-III isolates were from humans in North America and were pansusceptible to antibiotics. Newport was intermediate in population structure to the other serovars, which varied from a single monophyletic lineage in S. Enteritidis or S. Typhimurium to four discrete lineages within S. Paratyphi B. Both mutation and homologous recombination are responsible for diversification within each of these lineages, but the relative frequencies differed with the lineage. We conclude that serovars of S. enterica provide a variety of different population structures.


Comparison of crystalloids and colloids for hemodilution in a model of focal cerebral ischemia.
Forty dogs were subjected to 6 hours of occlusion of the left internal carotid and middle cerebral arteries. They were divided into two "hemodilution groups" of 13 dogs each and a control "nonhemodiluted group" of 14 dogs. Thirty minutes after arterial occlusion, isovolemic hemodilution was performed by phlebotomy and infusions of low-molecular weight (MW) dextran in one group and of lactated Ringer's solution in the other group. The animals were sacrificed 1 week after temporary arterial occlusion. Hemodilution reduced the hematocrit to a level of 33% to 34%, which lasted throughout the week in both groups. After hemodilution there was a very significant reduction in blood viscosity, plasma total protein content, and fibrinogen levels in both groups in the acute stage; these levels gradually returned to baseline by the end of the week. In the group with lactated Ringer's solution hemodilution, both osmotic and oncotic pressures were decreased by hemodilution in the acute stage. In the control and low-MW dextran groups, osmotic and oncotic pressure remained unaltered throughout the week. Hemodilution resulted in a slight decrease in mean arterial blood pressure in all groups in the acute stage, but there were no significant changes in central venous, pulmonary arterial, or pulmonary wedge pressures. During the week of study, there were no differences in the cardiac index and total blood volume between the groups, and no significant changes in hematological parameters with the exception of a slight increase in bleeding time immediately after hemodilution with low-MW dextran. Daily neurological assessment showed consistently poorer condition during the first 5 days in the group with lactated Ringer's solution compared to either the control group or the group receiving low-MW dextran. Based on Mann-Whitney U-testing, the infarct volume of the lactated Ringer's solution recipients, expressed as a percentage of the total volume of that hemisphere (median 15.7%, range 6.6% to 25.2%) was significantly larger than that of the group receiving low-MW dextran (median 2.2%, range 0% to 15.8%) and that of the control group (median 11.9%, range 0% to 39.9%). The results indicate that, in this model, hemodilution with colloids was beneficial, whereas hemodilution with crystalloids was deleterious. It is likely that the decrease in oncotic pressure observed after hemodilution with lactated Ringer's solution is one of the most important reasons for its detrimental effect.


Transcatheter arterial chemoembolization of liver tumors: effects of embolization protocol on injectable volume of chemotherapy and subsequent arterial patency.
The purpose of this study was to determine whether transcatheter arterial chemoembolization (TACE) protocol affects the total volume of chemotherapy injected into the liver as well as subsequent arterial patency. A total of 160 patients with primary or secondary liver cancer were treated with 3 different chemoembolization protocols at a single institution. Data were analyzed retrospectively. Group 1 (n = 36) consisted of slurry of chemotherapy, oil and polyvinyl alcohol particles (PVA), group 2 (n = 91), chemotherapy and oil followed by PVA, and group 3 (n = 33), chemotherapy and oil followed by Gelfoam pledgets. The total volume of chemotherapy injected into the liver was recorded. Arterial patency was determined during subsequent chemoembolizations. The mean percentage of total intended chemotherapy dose administered was 54.6% for group 1, 75.3% for group 2, and 80.6% for group 3. Arterial patency at follow-up angiography was 56% for group 1, 74% for group 2, and 81% for group 3. The slurry protocol (group 1) significantly reduced arterial patency and injectable volume of chemotherapy during TACE.


Cryofouling avoidance in the Antarctic scallop Adamussium colbecki.
The presence of supercooled water in polar regions causes anchor ice to grow on submerged objects, generating costly problems for engineered materials and life-endangering risks for benthic communities. The factors driving underwater ice accretion are poorly understood, and passive prevention mechanisms remain unknown. Here we report that the Antarctic scallop Adamussium colbecki appears to remain ice-free in shallow Antarctic marine environments where underwater ice growth is prevalent. In contrast, scallops colonized by bush sponges in the same microhabitat grow ice and are removed from the population. Characterization of the Antarctic scallop shells revealed a hierarchical micro-ridge structure with sub-micron nano-ridges which promotes directed icing. This concentrates the formation of ice on the growth rings while leaving the regions in between free of ice, and appears to reduce ice-to-shell adhesion when compared to temperate species that do not possess highly ordered surface structures. The ability to control the formation of ice may enable passive underwater anti-icing protection, with the removal of ice possibly facilitated by ocean currents or scallop movements. We term this behavior cryofouling avoidance. We posit that the evolution of natural anti-icing structures is a key trait for the survival of Antarctic scallops in anchor ice zones.


Postexposure prophylaxis, preexposure prophylaxis or universal test and treat: the strategic use of antiretroviral drugs to prevent HIV acquisition and transmission.
This review considers the use of antiretroviral drugs specifically to prevent HIV transmission. Antiretroviral therapy (ART) can be implemented for the protection of uninfected individuals both before (preexposure prophylaxis) and after (postexposure prophylaxis) exposure to HIV infection. Preexposure prophylaxis may be used coitally dependently when individuals are intermittently exposed or by continuous daily dosing for those constantly exposed; postexposure prophylaxis is used in 28-day courses. Alternatively, ART can be used strategically to reduce the viral load and consequent infectiousness of an HIV-infected individual, thereby limiting the risk of onward viral transmission. A policy of universal HIV testing to enhance the identification of all HIV-positive individuals followed by immediate treatment of all HIV-positive individuals, irrespective of their CD4 cell counts (universal test and treat), has been postulated as a potential tool capable of reducing HIV incidence at a population level. This concept represents a paradigm shift in the use of ART, targeting infectious individuals for prevention rather than protecting uninfected exposed populations. This strategy could have the advantage of preventing transmission and reducing HIV incidence at a population level, as well as delivering universal access to therapy for all people living with HIV and AIDS, potentially eliminating mother-to-child HIV transmission and limiting concomitant diseases such as tuberculosis. This review critically examines the scientific basis of ART for HIV prevention, summarizing the risks and opportunities of the potential expansion of ART for prevention. Specifically, we consider the evidences for and against targeting HIV-uninfected individuals compared with enhanced HIV testing and treatment of HIV-infected individuals in terms of impact on viral transmission.


Rupture of the femoral component and severe metallosis of the knee 10 years after unicompartmental knee arthroplasty (UKA): a case report.
A case of a 71-year-old man with femoral and tibial osteolysis and severe metallosis of the knee, resulting from abrasive wears of the metal components of a unicompartmental knee arthroplasty, that leaded to the rupture of the femoral component of the prosthesis is reported. An unicompartmental prosthesis, in a varus knee, was implanted in 2007. In March 2017, the patient felt that his knee was becoming increasingly unstable with pain and increasing disability. At clinical evaluation there was an effusion, 110° of flexion and - 10° of extension and a slight instability at the varus/valgus stress tests. BMI was 35. In a CT scan performed in June 2017 no signs of alteration were evident, but an X-Ray performed in January 2018 showed a rupture of the femoral component. A revision surgery was performed in February 2018. At the time of revision surgery, the synovitis and the metallosis were evident. A cemented total knee arthroplasty was performed. Samples of the fluid and surface did not show any bacterial growth. Histological examination confirmed the presence of a massive metallosis. The patient had a satisfactory rehabilitation. According to the literature, metallosis and rupture of the prosthetic components due to polyethylene wear after UKA is a common complication. In our case report the elevated BMI and varus knee accelerated the wear of the polyethylene. The aim of this case report is to enhance how an appropriate diagnosis (clinical and radiographic) and early treatment can lead to a successful result.


Epidemiology of alcohol dependence in UK primary care: Results from a large observational study using the Clinical Practice Research Datalink.
This study aims to investigate the incidence and annual presentation rates of alcohol dependence in general practice in the UK, and examine age-, gender-, socioeconomic-, and region-specific variation. We conducted a retrospective 'open' cohort study using the Clinical Practice Research Datalink (CPRD), an anonymised primary care database. Prior to data extraction, a case definition for alcohol dependence in CPRD was established using 47 Read codes, which included primary alcohol dependence and consequences of alcohol dependence. Directly standardised rates for incidence and annual presentation were calculated for each year between 1990 and 2013. Rates were compared by gender, age, UK home nation, and practice-level Index of Multiple Deprivation. The directly standardised annual incidence rates were 8.3 and 3.7 per 10,000 male and female patients, respectively. The estimated annual rates of presentation per 10,000 were 17.1 for males and 7.6 for females. Female to male rate ratios were: 0.40 (95% CI: 0.39-0.41) for incident cases; and 0.37 (95% CI: 0.36-0.39) for annual presentation. Rates were highest in those aged 35-54 for both measures and across genders, and lowest in those aged over 75 years. With England as the reference nation, Northern Ireland and Scotland had significantly higher rates for both measures. Patients from the most deprived areas had the highest incidence and annual presentation rates. There is unequal distribution of patients with severe alcohol dependence across population subgroups in general practice. Given the health and economic burden associated with dependent drinking, these data will be useful in informing future public health initiatives.


Bone Health and Osteoporosis.
Osteoporosis is characterized by low bone mass and microarchitectural deterioration of bone tissue leading to decreased bone strength and an increased risk of low-energy fractures. Central dual-energy X-ray absorptiometry measurements are the gold standard for determining bone mineral density. Bone loss is an inevitable consequence of the decrease in estrogen levels during and following menopause, but additional risk factors for bone loss can also contribute to osteoporosis in older women. A well-balanced diet, exercise, and smoking cessation are key to maintaining bone health as women age. Pharmacologic agents should be recommended in patients at high risk for fracture.


Tailoring and Evaluating an Intervention to Support Self-management After Stroke: Protocol for a Multi-case, Mixed Methods Comparison Study.
Self-management programs are recognized as a valuable approach to supporting people with long-term conditions, such as stroke, in managing their daily lives. Bridges Self-Management (Bridges) focuses on how practitioners interact and support patients' confidence, skills, and knowledge, and it is an example of a complex intervention. Bridges has been developed and used across multiple health care pathways in the United Kingdom and is theoretically informed by social cognition theory and self-efficacy principles. Evidence shows that self-management programs based on the construct of self-efficacy can be effective. There is still much to learn about how health care services or pathways should implement support for self-management in a sustainable way and whether this implementation process is different depending on the context or culture of the team or service provided. The aim of this study is to tailor and evaluate an intervention (Bridges) to support self-management after stroke in a Swedish context. We will use a pretest-posttest design with a case study approach to evaluate the feasibility and implementation of self-management support in two stroke settings. This project includes a complex intervention and depends on the actions of individuals, different contexts, and the adaptation of behavior over time. A mixed methods approach was chosen to understand both outcomes and mechanisms of impact. Data collection will comprise outcome measurements and assessment tools as well as qualitative interviews. Data will be collected concurrently and integrated into a mixed methods design. Recruitment and data collection for the first site of the project ran from September 1, 2021, to January 17, 2022. The intervention at the first site was conducted from November 1, 2021, to March 5, 2022. The evaluation will start after the implementation phase. The second site has been recruited, and the baseline data collection will start in spring 2022. The intervention will start in early autumn 2022. Data collection will be completed by the end of 2022. This study represents a unique, highly relevant, and innovative opportunity to maximize knowledge and minimize practice gaps in rehabilitation stroke care. The study will produce robust data on the intervention and in-depth data on the contextual factors and mechanisms related to the feasibility of the intervention and for whom it is feasible. Bridges has been used in the United Kingdom for more than 10 years, and this study will explore its contextualization and implementation within a Swedish stroke environment. The evaluation will study results at the patient, staff, and organizational levels and provide recommendations for the adoption and refinement of future efforts to support self-management. DERR1-10.2196/37672.


Mitochondria, metabolic disturbances, oxidative stress and the kynurenine system, with focus on neurodegenerative disorders.
The mitochondria have several important functions in the cell. A mitochondrial dysfunction causes an abatement in ATP production, oxidative damage and the induction of apoptosis, all of which are involved in the pathogenesis of numerous disorders. This review focuses on mitochondrial dysfunctions and discusses their consequences and potential roles in the pathomechanism of neurodegenerative disorders. Other pathogenetic factors are also briefly surveyed. The second part of the review deals with the kynurenine metabolic pathway, its alterations and their potential association with cellular energy impairment in certain neurodegenerative diseases. During energy production, most of the O(2) consumed by the mitochondria is reduced fully to water, but 1-2% of the O(2) is reduced incompletely to give the superoxide anion (O(2)(-)). If the function of one or more respiratory chain complexes is impaired for any reason, the enhanced production of free radicals further worsens the mitochondrial function by causing oxidative damage to macromolecules, and by opening the mitochondrial permeability transition pores thereby inducing apoptosis. These high-conductance pores offer a pathway which can open in response to certain stimuli, leading to the induction of the cells' own suicide program. This program plays an essential role in regulating growth and development, in the differentiation of immune cells, and in the elimination of abnormal cells from the organism. Both failure and exaggeration of apoptosis in a human body can lead to disease. The increasing amount of superoxide anions can react with nitric oxide to yield the highly toxic peroxynitrite anion, which can destroy cellular macromolecules. The roles of oxidative, nitrative and nitrosative damage are discussed. Senescence is accompanied by a higher degree of reactive oxygen species production, and by diminished functions of the endoplasmic reticulum and the proteasome system, which are responsible for maintenance of the normal protein homeostasis of the cell. In the event of a dysfunction of the endoplasmic reticulum, unfolded proteins aggregate in it, forming potentially toxic deposits which tend to be resistant to degradation. Cells possess adaptive mechanisms with which to avoid the accumulation of incorrectly folded proteins. These involve molecular chaperones that fold proteins correctly, and the ubiquitin proteasome system which degrades misfolded, unwanted proteins. Both the endoplasmic reticulum and the ubiquitin proteasome system fulfill cellular protein quality control functions. The kynurenine system: Tryptophan is metabolized via several pathways, the main one being the kynurenine pathway. A central compound of the pathway is kynurenine (KYN), which can be metabolized in two separate ways: one branch furnishing kynurenic acid, and the other 3-hydroxykynurenine and quinolinic acid, the precursors of NAD. An important feature of kynurenic acid is the fact that it is one of the few known endogenous excitatory amino acid receptor blockers with a broad spectrum of antagonistic properties in supraphysiological concentrations. One of its recently confirmed sites of action is the alpha7-nicotinic acetylcholine receptor and interestingly, a more recently identified one is a higher affinity positive modulatory binding site at the AMPA receptor. Kynurenic acid has proven to be neuroprotective in several experimental settings. On the other hand, quinolinic acid is a specific agonist at the N-methyl-d-aspartate receptors, and a potent neurotoxin with an additional and marked free radical-producing property. There are a number of neurodegenerative disorders whose pathogenesis has been demonstrated to involve multiple imbalances of the kynurenine pathway metabolism. These changes may disturb normal brain function and can add to the pathomechanisms of the diseases. In certain disorders, there is a quinolinic acid overproduction, while in others the alterations in brain kynurenic acid levels are more pronounced. A more precise knowledge of these alterations yields a basis for getting better therapeutic possibilities. The last part of the review discusses metabolic disturbances and changes in the kynurenine metabolic pathway in Parkinson's, Alzheimer's and Huntington's diseases.


Caregiver Experiences With Oral Bilingualism in Children Who Are Deaf and Hard of Hearing in the United States: Impact on Child Language Proficiency.
Best practices recommend promoting the use of the home language and allowing caregivers to choose the language(s) that they want to use with their child who is deaf or hard of hearing (DHH). We examined whether Spanish-speaking caregivers of children who are DHH receive professional recommendations on oral bilingualism that follow best practices. We also assessed whether professional recommendations, caregiver beliefs, and language practices had an impact on child language(s) proficiency. Sixty caregivers completed a questionnaire on demographic questions, language(s) use and recommendations, beliefs on bilingualism, and child language proficiency measures in English, Spanish, and American Sign Language (ASL). Professional recommendations on oral bilingualism were reported descriptively, and linear regression was used to identify the predictors of child language(s) proficiency. We found that only 23.3% of the caregivers were actively encouraged to raise their child orally bilingual. Language practices predicted child proficiency in each language (English, Spanish, and ASL), but professional recommendations and caregiver beliefs did not. Our results revealed that most caregivers received recommendations that do not follow current best practices. Professional training is still needed to promote bilingualism and increase cultural competence when providing services to caregivers who speak languages different from English. https://doi.org/10.23641/asha.21644846.


FATAL ACINETOBACTER BAUMANNII INFECTION IN THE CRITICALLY ENDANGERED EUROPEAN MINK (MUSTELA LUTREOLA).
The present study reports the first case of fatal Acinetobacter baumannii infection in the critically endangered European mink ( Mustela lutreola ). Gross examination revealed a severe, diffuse hemorrhagic pneumonia and generalized congestion as main features. Microscopically, the main lesions were an acute, severe fibrinous-hemorrhagic pneumonia associated with proliferation of coccobacilli and generalized acute-subacute congestion. Cultures yielded A. baumannii ; the species was confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and the strain presented a multidrug-resistant pattern. The results are not only of conservation concern but also of public health concern given A. baumannii is one of the most important pathogens implicated in nosocomial infections in humans.


The Weak Reality That Makes Quantum Phenomena More Natural: Novel Insights and Experiments.
While quantum reality can be probed through measurements, the Two-State Vector Formalism (TSVF) reveals a subtler reality prevailing between measurements. Under special pre- and post-selections, odd physical values emerge. This unusual picture calls for a deeper study. Instead of the common, wave-based picture of quantum mechanics, we suggest a new, particle-based perspective: Each particle possesses a definite location throughout its evolution, while some of its physical variables (characterized by deterministic operators, some of which obey nonlocal equations of motion) are carried by "mirage particles" accounting for its unique behavior. Within the time interval between pre- and post-selection, the particle gives rise to a horde of such mirage particles, of which some can be negative. What appears to be "no-particle", known to give rise to interaction-free measurement, is in fact a self-canceling pair of positive and negative mirage particles, which can be momentarily split and cancel out again. Feasible experiments can give empirical evidence for these fleeting phenomena. In this respect, the Heisenberg ontology is shown to be conceptually advantageous compared to the Schrödinger picture. We review several recent advances, discuss their foundational significance and point out possible directions for future research.


Recovery of infectious bluetongue virus from RNA.
Bluetongue virus (BTV) is an insect-vectored emerging pathogen of ruminants with the potential for devastating economic impact on European agriculture. BTV and many other members of the Reoviridae have remained stubbornly refractory to the development of methods for the rescue of infectious virus from cloned nucleic acid (reverse genetics). Partially disassembled virus particles are transcriptionally active, synthesizing viral transcripts in the cytoplasm of infected cells, in essence delivering viral nucleic acids in situ. With the goal of generating a reverse-genetics system for BTV, we examined the possibility of recovering infectious BTV by the transfection of BSR cells with BTV transcripts (single-stranded RNA [ssRNA]) synthesized in vitro using BTV core particles. Following transfection, viral-protein synthesis was detected by immunoblotting, and confocal examination of the cells showed a punctate cytoplasmic distribution of inclusion bodies similar to that seen in infected cells. Viral double-stranded RNA (dsRNA) was isolated from ssRNA-transfected cells, demonstrating that replication of the ssRNA had occurred. Additionally, infectious virus was present in the medium of transfected cells, as demonstrated by the passage of infectivity in BSR cells. Infectivity was sensitive to single-strand-specific RNase A, and cotransfection of genomic BTV dsRNA with transcribed ssRNA demonstrated that the ssRNA species, rather than dsRNA, were the active components. We conclude that it is possible to recover infectious BTV wholly from ssRNA, which suggests a means for establishing helper virus-independent reverse-genetics systems for members of the Reoviridae.


Experimental disturbances reveal group-level costs of social instability.
In group-living species, social stability is an important trait associated with the evolution of complex behaviours such as cooperation. While the drivers of stability in small groups are relatively well studied, little is known about the potential impacts of unstable states on animal societies. Temporary changes in group composition, such as a social group splitting and recombining (i.e. a disturbance event), can result in individuals having to re-establish their social relationships, thus taking time away from other tasks such as foraging or vigilance. Here, we experimentally split socially stable groups of captive zebra finches (Taeniopygia guttata), and quantified the effects of repeated disturbance events on (1) group foraging efficiency, and (2) co-feeding associations when subgroups were recombined. We found that the efficiency of groups to deplete a rich, but ephemeral, resource patch decreased after just a single short disturbance event. Automated tracking of individuals showed that repeated disturbances reduced efficiency by causing social relationships to become more differentiated and weaker, resulting in fewer individuals simultaneously accessing the patch. Our experiment highlights how short-term disturbances can severely disrupt social structure and group functionality, revealing potential costs associated with group instability that can have consequences for the evolution of animal societies.


Video capture and editing as a tool for the storage, distribution, and illustration of morphological characters of nematodes.
Morphological identification and detailed observation of nematodes usually requires permanent slides, but these are never truly permanent and often prevent the same specimens to be used for other purposes. To efficiently record the morphology of nematodes in a format that allows easy archiving, editing, and distribution, we have assembled two micrographic video capture and editing (VCE) configurations. These assemblies allow production of short video clips that mimic multifocal observation of nematode specimens through a light microscope. Images so obtained can be used for training, management, and online access of "virtual voucher specimens" in taxonomic collections, routine screening of fixed or unfixed specimens, recording of ephemeral staining patterns, or recording of freshly dissected internal organs prior to their decomposition. We provide an overview of the components and operation of both of our systems and evaluate their efficiency and image quality. We conclude that VCE is a highly versatile approach that is likely to become widely used in nematology research and teaching.


Prevalence and Predictors of Poor Recovery from Mild Traumatic Brain Injury.
Although most patients with mild traumatic brain injury (mTBI) recover within 3 months, a subgroup of patients experience persistent symptoms. Yet, the prevalence and predictors of persistent dysfunction in patients with mTBI remain poorly understood. In a longitudinal study, we evaluated predictors of symptomatic and cognitive dysfunction in adolescents and young adults with mTBI, compared with two control groups-patients with orthopedic injuries and healthy uninjured individuals. Outcomes were assessed at 3 months post-injury. Poor symptomatic outcome was defined as exhibiting a symptom score higher than 90% of the orthopedic control (OC) group, and poor cognitive outcome was defined as exhibiting cognitive performance poorer than 90% of the OC group. At 3 months post-injury, more than half of the patients with mTBI (52%) exhibited persistently elevated symptoms, and more than a third (36.4%) exhibited poor cognitive outcome. The rate of high symptom report in mTBI was markedly greater than that of typically developing (13%) and OC (17%) groups; the proportion of those with poor cognitive performance in the mTBI group exceeded that of typically developing controls (15.8%), but was similar to that of the OC group (34.9%). Older age at injury, female sex, and acute symptom report were predictors of poor symptomatic outcome at 3 months. Socioeconomic status was the only significant predictor of poor cognitive outcome at 3 months.


The value of purpose built mental health facilities: Use of the Ward Atmosphere Scale to gauge the link between milieu and physical environment.
This study investigated changes in the 'atmosphere' of an acute adult mental health setting following relocation to a new purpose-built facility. The Ward Atmosphere Scale (WAS) was designed and validated for specific use in hospital-based psychiatric facilities, and measures several dimensions of an environment. In this study, the WAS was administered to consumers and staff at periods before and also after their relocation to a new purpose-built acute adult mental health facility. There were significant improvements in the physical atmosphere of the new facility, when compared with the old facility. In terms of ward atmosphere, however, improvements were seen to occur in only a small number of measures and there were minor differences between consumers' and staff perspectives on some indicators. Interestingly, it was found that consumers noted less 'staff control' in the new setting, raising the question of the differences in understanding of control. For staff only, there was a perception of greater levels of consumer 'involvement' in the new facility. Despite the minor differences in perception, the study does confirm that architecture is an important influence on the 'atmosphere' of a health facility, for both staff and consumers.


Mastermind mediates chromatin-specific transcription and turnover of the Notch enhancer complex.
Signaling through the Notch pathway activates the proteolytic release of the Notch intracellular domain (ICD), a dedicated transcriptional coactivator of CSL enhancer-binding proteins. Here we show that chromatin-dependent transactivation by the recombinant Notch ICD-CBF1 enhancer complex in vitro requires an additional coactivator, Mastermind (MAM). MAM provides two activation domains necessary for Notch signaling in mammalian cells and in Xenopus embryos. We show that the central MAM activation domain (TAD1) recruits CBP/p300 to promote nucleosome acetylation at Notch enhancers and activate transcription in vitro. We also find that MAM expression induces phosphorylation and relocalization of endogenous CBP/p300 proteins to nuclear foci in vivo. Moreover, we show that coexpression with MAM and CBF1 strongly enhances phosphorylation and proteolytic turnover of the Notch ICD in vivo. Enhanced phosphorylation of the ICD and p300 requires a glutamine-rich region of MAM (TAD2) that is essential for Notch transcription in vivo. Thus MAM may function as a timer to couple transcription activation with disassembly of the Notch enhancer complex on chromatin.


Diffraction analysis of Doppler signal characteristics for a cross-beam laser Doppler velocimeter.
Based on scalar diffraction theory, single particle scattering characteristics for a cross-beam laser Doppler velocimeter (LDV) have been computed for different particle sizes under varied instrumentation configurations. The modulating component of the scattered signal has been shown to depend upon particle size, shape, and collecting aperture for a given probe volume fringe spacing. Experimental verifications of some of the predictions are presented, and some of the limitations using an LDV as a particle sizing instrument are discussed.


Impact of Endometrial Preparation Protocols for Frozen Embryo Transfer on Live Birth Rates.
It has been reported that a natural cycle (NC) is similar to or even better than hormone replacement therapy (HRT) in patients with regular cycles who undergo frozen embryo transfer (FET). Hundreds of FETs are managed yearly in our clinic. Scheduling these cycles is critical in a busy unit like ours. This is why we have to prove if a NC really shows a better outcome than other endometrium preparation protocols. Hence we carried out a prospective study between June 2011 and June 2012, which included 530 patients (570 FET cycles) randomly allocated to two study groups: Group 1 (n=280 cycles), artificial cycle (HRT); or group 2 (n=290 cycles), natural cycle. Natural cycles were later divided into two groups: 169 patients scheduled with human chorionic gonadotropin (hCG) and 121 with endogenous luteinizing hormone (LH) surge. The inclusion criteria were: age <39 years, regular menstrual cycles (26-35 days), and previous IVF cycle with embryo cryopreservation. The exclusion criteria were polycystic ovarian syndrome and endometriosis stage III/IV. No statistical differences were found in the baseline characteristics among groups, nor between implantation or ongoing pregnancy rates (30.8% HRT group; 32.7% hCG group; 34.5% LH surge group). However, a higher miscarriage rate was observed in the HRT group when compared to hCG or LH surge (21.2% versus 12.9% versus 11.1%, P<0.01). Live birth rates were similar among groups, as were perinatal outcomes, for rates of natural delivery and weight and length of newborns. We conclude that scheduling FET with HRT on weekdays and avoiding work overload at weekends prove efficient and safe in cycle outcome terms. Another reason for the convenience of an HRT protocol is having fewer visits to the clinic compared to natural cycle protocols.


Genotyping of Babesia bigemina from cattle from a non-endemic area (Switzerland).
In August 2002, bovine anaplasmosis and concurrent infections with Mycoplasma sp. and piroplasms were reported in a cattle herd in an alpine region of Switzerland. The piroplasms were identified by PCR/sequencing of part of the 18S rRNA gene as Babesia bigemina and Theileria of the buffeli/sergenti/orientalis-complex, which have never been diagnosed in Switzerland before. The B. bigemina isolate was genetically characterised at two loci and compared with isolates from Italy, Spain, Turkey, Kenya and Mexico. Analysis of the internal transcribed spacer 2 (ITS2) of the rRNA genes revealed high polymorphism not only among the isolates but even within the isolates, and the presence of two types of the ITS2 in every isolate was confirmed. A dendrogram based on ITS2 sequences showed that the Swiss isolate was most closely related to a Spanish isolate but no sequences of the isolate from Switzerland were identical to any of the other isolates. The isolate from Italy was not positioned in the same cluster as the Swiss and the Spanish isolate. This had been anticipated as the nearest known endemic area of B. bigemina in Central Italy. Sequence analysis of the rhoptry-associated protein-1c gene (rap1c) confirmed the similarity of the Swiss and Spanish isolate. Hence, our molecular analyses of the Swiss B. bigemina isolate did not unequivocally track its geographical origin and the way of introduction remains obscure.


Cesarean section: requested mode of delivery?.
To constitute accurate policies for reducing the cesarean section (C/S) the authors evaluated the attitudes and knowledge of health workers and public population towards the mode of delivery, C/S on demand, and delivery complications in a large population. 1,892 female volunteers in reproductive age were enrolled in the study and 589 of them were health workers. Patients were evaluated with questionnaire about their delivery mode and their answers were analyzed. The overall cesarean rate of the study population was 45.4%. This rate were 51.4% and 28.2%, respectively, for the health workers and public group (p < 0.001). Medical indication ratio ivere 57.7% and 40.1% for the healthcare group and the public population respectively and 20.2% of health workers and 13.9% of the public group had C/S by their preference without any medical indications (p < 0.001). C/S rate is high in Turkey and an action plan is needed to decrease the rate. When a patient's preference towards the mode of the delivery is C/S on demand, obstetricians, in their capacity as patient advocate, should help guide their patient through the sophisticated detailed medical information toward a decision that respects both the patient's attitude and the physician's obligation to optimize the health of both the mother and the newborn.