Cachectin/tumor necrosis factor induces cachexia, anemia, and inflammation.
Cachexia is a potentially lethal syndrome of unknown etiology characterized by anorexia, weight loss, and protein wasting that frequently complicates the treatment of chronic inflammation and cancer. Cachectin/TNF was isolated during the search for a humoral mediator of cachexia and found to stimulate the breakdown of energy stores from adipocytes and myocytes in vitro, but the chronic effects of the monokine in vivo are not known. Sublethal doses of recombinant human cachectin administered twice daily for 7-10 d caused cachexia in rats, as evidenced by reduced food intake, weight loss, and depletion of whole-body lipid and protein stores. Significant anemia is also observed and found to be the result of decreased red blood cell mass, not expanded plasma volume. Leukocytosis and histopathological evidence of tissue injury and inflammation are observed in several organs, including omentum, liver, spleen, and heart. These data suggests that the exposure of the normal host to cachectin is capable of inducing a pathophysiological syndrome of cachexia, anemia, and inflammation similar to that observed during inflammatory states or malignancy.


Salivary cortisol in two professions: daily cortisol profiles in school teachers and firefighters.
It's indicated negative-perceived stress could induce worse health status and change of cortisol secretion. To assess salivary cortisol levels in two occupations with a high psychosocial workload, but different features, teachers and firefighters. The study population consisted of 142 school teachers and 136 firefighters. Four saliva samples were collected from pedagogical participants during their busiest workday. The cortisol measures used were: morning values, evening values, slope of decline, ratio (evening value divided by morning value), and area under the curve (AUC). The salivary cortisol measurements in both genders were almost equal regarding morning values, slope, and AUC increase. Evening values were lower and the relative reactivity was higher (lower ratio) for female teachers, compared to male teachers. There was a tendency of a lower total daytime output of cortisol (AUC ground) among female teachers. Firefighters had lower levels of cortisol, lower total daytime output, and higher relative reactivity (lower ratio), but lower absolute reactivity, regarding both slope and AUC increase. Overall, male teachers might be the group most affected by stress in this study, even if some of their cortisol values were almost equal to the female teachers' values. Male teachers also seemed to be more affected by stress, according to salivary cortisol, compared to male firefighters, even if there were some inconsistencies.


Meaningful silences: how dopamine listens to the ACh pause.
Mesostriatal dopaminergic neurons (DANs) and striatal cholinergic neurons (tonically active neurons, TANs) participate in signalling the behavioural or reward-related significance of stimuli in the environment. An antagonistic balance between dopamine (DA) and ACh is well known to regulate postsynaptic signal integration in the striatum. Recent findings have revealed additional presynaptic ACh-DA interactions of previously unappreciated sophistication. Striatal ACh acts presynaptically to polarize powerfully how opposing DAN activities are transduced into DA release. Furthermore, characteristic reward-related activities of TANs and DANs are temporally coincident but differently variant with reward probability. Reward-related DA signals could therefore be governed by the concomitant activity in TANs. This article discusses the dynamic implications for DA signalling when these phenomena act in concert. TAN pauses might powerfully enhance the contrast, or salience, of DA signals offered by reward-related bursts, and even by reward omission-related pauses, in DANs. Through such mechanisms, TAN-DAN interactions would be functionally cooperative.


Accuracy of Optical Heart Rate Sensing Technology in Wearable Fitness Trackers for Young and Older Adults: Validation and Comparison Study.
Wearable fitness trackers are devices that can record and enhance physical activity among users. Recently, photoplethysmography (PPG) devices that use optical heart rate sensors to detect heart rate in real time have become popular and help in monitoring and controlling exercise intensity. Although the benefits of using optical heart rate monitors have been highlighted through studies, the accuracy of the readouts these commercial devices generate has not been widely assessed for different age groups, especially for the East Asian population with Fitzpatrick skin type III or IV. This study aimed to examine the accuracy of 2 wearable fitness trackers with PPG to monitor heart rate in real time during moderate exercise in young and older adults. A total of 20 young adults and 20 older adults were recruited for this study. All participants were asked to undergo a series of sedentary and moderate physical activities using indoor aerobic exercise equipment. In this study, the Polar H7 chest-strapped heart rate monitor was used as the criterion measure in 2 fitness trackers, namely Xiaomi Mi Band 2 and Garmin Vivosmart HR+. The real-time, second-by-second heart rate data obtained from both devices were recorded using the broadcast heart rate mode. To critically analyze the results, multiple statistical parameters including the mean absolute percentage error (MAPE), Lin concordance correlation coefficient (CCC), intraclass correlation coefficient, the Pearson product moment correlation coefficient, and the Bland-Altman coefficient were determined to examine the performances of the devices. Both test devices exhibited acceptable overall accuracy as heart rate sensors based on several statistical tests. Notably, the MAPE values were below 10% (the designated threshold) in both devices (GarminYoung=3.77%; GarminSenior=4.73%; XiaomiYoung=7.69%; and XiaomiSenior=6.04%). The scores for reliability test of CCC for Garmin were 0.92 (Young) and 0.80 (Senior), whereas those for Xiaomi were 0.76 (Young) and 0.73 (Senior). However, the results obtained using the Bland-Altman analysis indicated that both test optical devices underestimated the average heart rate. More importantly, the study documented some unexpected outlier readings reported by these devices when used on certain participants. The study reveals that commonly used optical heart rate sensors, such as the ones used herein, generally produce accurate heart rate readings irrespective of the age of the user. However, users should avoid relying entirely on these readings to indicate exercise intensities, as these devices have a tendency to produce erroneous, extreme readings, which might misinterpret the real-time exercise intensity. Future studies should therefore emphasize the occurrence rate of such errors, as this will likely benefit the development of improved models of heart rate sensors.


Infective endocarditis in the Netherlands: current epidemiological profile and mortality : An analysis based on partial ESC EORP collected data.
Infective endocarditis (IE) is associated with a high in-hospital and long term mortality. Although progress has been made in diagnostic approach and management of IE, morbidity and mortality of IE remain high. In the latest European guidelines, the importance of the multi-modality imaging in diagnosis and follow up of IE is emphasized. The aim was to provide information regarding mortality and adverse events of IE, to determine IE characteristics and to assess current use of imaging in the diagnostic workup of IE. This is a prospective observational cohort study. We used data from the EURO-ENDO registry. Seven hospitals in the Netherlands have participated and included patients with IE between April 2016 and April 2018. A total of 139 IE patients were included. Prosthetic valve endocarditis constituted 32.4% of the cases, cardiac device related IE 7.2% and aortic root prosthesis IE 3.6%. In-hospital mortality was 14.4% (20 patients) and one-year mortality was 21.6% (30 patients). The incidence of embolic events under treatment was 16.5%, while congestive heart failure or cardiogenic shock occurred in 15.1% of the patients. Transthoracic and transoesophageal echocardiography were performed most frequently (97.8%; 81.3%) and within 3 days after IE suspicion, followed by 18F‑fluorodeoxyglucose positron emission tomography/computed tomography (45.3%) within 6 days and multi-slice computed tomography (42.4%) within 7 days. We observed a high percentage of prosthetic valve endocarditis, rapid and extensive use of imaging and a relatively low in-hospital and one-year mortality of IE in the Netherlands. Limitations include possible selection bias.


Short-term, high-fat overfeeding impairs glycaemic control but does not alter gut hormone responses to a mixed meal tolerance test in healthy, normal-weight individuals.
Obesity is undoubtedly caused by a chronic positive energy balance. However, the early metabolic and hormonal responses to overeating are poorly described. This study determined glycaemic control and selected gut hormone responses to nutrient intake before and after 7 d of high-fat overfeeding. Nine healthy individuals (five males, four females) performed a mixed meal tolerance test (MTT) before and after consuming a high-fat (65 %), high-energy (+50 %) diet for 7 d. Measurements of plasma glucose, NEFA, acylated ghrelin, glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP) and serum insulin were taken before (fasting) and at 30-min intervals throughout the 180-min MTT (postprandial). Body mass increased by 0·79 (sem 0·14) kg after high-fat overfeeding (P<0·0001), and BMI increased by 0·27 (sem 0·05) kg/m2 (P=0·002). High-fat overfeeding also resulted in an 11·6 % increase in postprandial glucose AUC (P=0·007) and a 25·9 % increase in postprandial insulin AUC (P=0·005). Acylated ghrelin, GLP-1 and GIP responses to the MTT were all unaffected by the high-fat, high-energy diet. These findings demonstrate that even brief periods of overeating are sufficient to disrupt glycaemic control. However, as the postprandial orexigenic (ghrelin) and anorexigenic/insulintropic (GLP-1 and GIP) hormone responses were unaffected by the diet intervention, it appears that these hormones are resistant to short-term changes in energy balance, and that they do not play a role in the rapid reduction in glycaemic control.


Models of interaction between metabolic genes and environmental exposure in cancer susceptibility.
Polymorphic metabolic genes that confer enhanced genetic susceptibility to the carcinogenic effects of certain environmental carcinogens act according to a type 2 interaction between genetic and environmental risk factors. This type of interaction, for which the gene has no effect on disease outcome by itself but only modifies the risk associated with exposure, must be treated differently from other types of gene-environment interaction. We present a method to analyze different dose effects often seen in studies involving these genes. We define a low exposure-gene effect, when a greater degree of gene environment interaction appears at lower doses of exposure (the interaction follows an inverse dose function), and a converse high exposure-gene effect, when the interaction increases as a function of dose. Using a standard logistic regression model, we define a new term, alpha, that can be determined asa function of exposure dose in order to analyze epidemiological studies for the type of exposure-gene effect. These models are illustrated by the use of hypothetical case-control data as well as examples from the literature.


The HEART Camp Exercise Intervention Improves Exercise Adherence, Physical Function, and Patient-Reported Outcomes in Adults With Preserved Ejection Fraction Heart Failure.
Despite exercise being one of few strategies to improve outcomes for individuals with heart failure with preserved ejection fraction (HFpEF), exercise clinical trials in HFpEF are plagued by poor interventional adherence. Over the last 2 decades, our research team has developed, tested, and refined Heart failure Exercise And Resistance Training (HEART) Camp, a multicomponent behavioral intervention to promote adherence to exercise in HF. We evaluated the effects of this intervention designed to promote adherence to exercise in HF focusing on subgroups of participants with HFpEF and heart failure with reduced ejection fraction (HFrEF). This randomized controlled trial included 204 adults with stable, chronic HF. Of those enrolled, 59 had HFpEF and 145 had HFrEF. We tested adherence to exercise (defined as ≥120 minutes of moderate-intensity [40%-80% of heart rate reserve] exercise per week validated with a heart rate monitor) at 6, 12, and 18 months. We also tested intervention effects on symptoms (Patient-Reported Outcomes Measurement Information System-29 and dyspnea-fatigue index), HF-related health status (Kansas City Cardiomyopathy Questionnaire), and physical function (6-minute walk test). Participants with HFpEF (n = 59) were a mean of 64.6 ± 9.3 years old, 54% male, and 46% non-White with a mean ejection fraction of 55 ± 6%. Participants with HFpEF in the HEART Camp intervention group had significantly greater adherence compared with enhanced usual care at both 12 (43% vs 14%, phi = 0.32, medium effect) and 18 months (56% vs 0%, phi = 0.67, large effect). HEART Camp significantly improved walking distance on the 6-minute walk test (η2 = 0.13, large effect) and the Kansas City Cardiomyopathy Questionnaire overall (η2 = 0.09, medium effect), clinical summary (η2 = 0.16, large effect), and total symptom (η2 = 0.14, large effect) scores. In the HFrEF subgroup, only patient-reported anxiety improved significantly in the intervention group. A multicomponent, behavioral intervention is associated with improvements in long-term adherence to exercise, physical function, and patient-reported outcomes in adults with HFpEF and anxiety in HFrEF. Our results provide a strong rationale for a large HFpEF clinical trial to validate these findings and examine interventional mechanisms and delivery modes that may further promote adherence and improve clinical outcomes in this population. URL: https://clinicaltrials.gov/. Unique identifier: NCT01658670.


Histone Peptide Recognition by KDM5B-PHD1: A Case Study.
A detailed understanding of the energetic contributions to histone peptide recognition would be valuable for a better understanding of chromatin anchoring mechanisms and histone diagnostic design. Here, we probed the energetic contributions to recognize the same unmodified histone H3 by three different plant homeodomain (PHD) H3K4me0 readers: hKDM5B-PHD1 (first PHD finger of hKDM5B), hBAZ2A-PHD, and hAIRE-PHD1. The energetic contributions of residues differ significantly from one complex to the next. For example, H3K4A substitution completely aborts the formation of the hAIRE-histone peptide complex, while it has only a small destabilizing effect on binding of the other readers, even though H3K4 methylation disrupts all three complexes. Packing density suggests that methylation of more tightly packed Lys/Arg residues can disrupt binding, even if the energetic contribution is small. The binding behavior of hKDM5B-PHD1 and hBAZ2A-PHD is similar, and like PHD H3R2 readers, both possess a pair of Asp residues in the treble clef for interaction with H3R2. PHD subtype sequences, especially the tandem PHD-PHD fingers, show enrichment in the treble clef Asp residues, suggesting that it is a subtype-specific property. These Asp residues make significant energetic contributions to the formation of the hKDM5B-histone peptide complex, suggesting that there are interactions in addition to those reported in the recent NMR structure. However, the presence of the treble clef Asp in PHD sequences may not always be sufficient for histone peptide binding. This study showcases reader-histone peptide interactions in the context of residue conservation, energetic contributions, interfacial packing, and sequence-based reader subtype predictability.


A novel delta-subdivision proteobacterial lineage from the lower ocean surface layer.
A small-subunit ribosomal RNA (16S rRNA) gene lineage (SAR324) affiliated with the delta-subdivision of the class Proteobacteria (DP) was discovered in a 16S rRNA gene clone library prepared from a water sample collected from 250 m in the western Sargasso Sea. This clone library of nearly full-length amplicons of bacterial 16S rRNA genes has been the subject of previous studies aimed at identifying bacteria that inhibit the lower ocean surface layer. The novel lineage was identified by randomly sequencing clones that did not hybridize to oligonucleotide probes specific for several abundant bacterioplankton groups identified in previous studies. Phylogenetic analysis indicated that SAR324 was most closely affiliated with the DP, although it showed no specific relationship to any DP 16S rRNA genes in databases. Eight of the clones in the library of 148 clones were identified as members of the SAR324 lineage by hybridization to an oligonucleotide probe specific for SAR324. Subsequent hybridizations showed that the SAR324 group is stratified in the lower surface layer of both the Atlantic and Pacific Oceans, with maxima between 160 and 500 m. The repeated discovery of sequences belonging to different gene clusters with similar distributions in this region of the water column suggests that microbial communities in the lower surface layer may be functionally specialized.


[Neonatal cystic fibrosis screening program in the state of Paraná: evaluation 30 months after implementation].
To present and analyze the results of the National Neonatal Cystic Fibrosis Screening Program in Paraná, 30 months after its implementation. This is a descriptive study, with an analysis of the data from the screening of around 98% of all neonates in the period from September 2001 to April 2004, undertaken at the Neonatal Screening Program laboratory of the Fundação Ecumênica de Proteção ao Excepcional do Paraná. Blood samples for the Guthrie test were collected on hospital discharge, ideally between the second and sixth days postpartum, and filter papers were sent for immunoreactive trypsin assay by the immunofluorometric method. Children whose immunoreactive trypsin assay results were > or = 70 ng/ml for two distinct samples during the first 30 days of life, were referred for sweat conductivity testing by the Wescor method. In cases when the result was greater than 50 mMol/l quantitative chlorine and/or sodium in sweat was assayed (iontophoresis with pilocarpine). From a total of 456,982 tests, 4,028 (0.9%) children presented a first immunoreactive trypsin assay above the cutoff point set. Four hundred and seventy-eight of these (12.5%) also had a second blood sample assayed with immunoreactive trypsin above 70 ng/ml and 56 (11.7%) of these were referred to specialized clinics after their sweat conductivity test results were above 50 mMol/l and 48 (0.01% of the total number of children screened) had a diagnosis of cystic fibrosis confirmed. The incidence for the state of Paraná was 1:9,520, although some children have not yet been fully investigated. Neonatal screening for cystic fibrosis in the State of Paraná, in accordance with Health Ministry directives, was a pioneering initiative for Brazil. Many patients were diagnosed early, even asymptomatic ones, which is a challenge to improving prognosis with this fatal disease.


Long-term exposure to outdoor and household air pollution and blood pressure in the Prospective Urban and Rural Epidemiological (PURE) study.
Exposure to air pollution has been linked to elevated blood pressure (BP) and hypertension, but most research has focused on short-term (hours, days, or months) exposures at relatively low concentrations. We examined the associations between long-term (3-year average) concentrations of outdoor PM2.5 and household air pollution (HAP) from cooking with solid fuels with BP and hypertension in the Prospective Urban and Rural Epidemiology (PURE) study. Outdoor PM2.5 exposures were estimated at year of enrollment for 137,809 adults aged 35-70 years from 640 urban and rural communities in 21 countries using satellite and ground-based methods. Primary use of solid fuel for cooking was used as an indicator of HAP exposure, with analyses restricted to rural participants (n = 43,313) in 27 study centers in 10 countries. BP was measured following a standardized procedure and associations with air pollution examined with mixed-effect regression models, after adjustment for a comprehensive set of potential confounding factors. Baseline outdoor PM2.5 exposure ranged from 3 to 97 μg/m3 across study communities and was associated with an increased odds ratio (OR) of 1.04 (95% CI: 1.01, 1.07) for hypertension, per 10 μg/m3 increase in concentration. This association demonstrated non-linearity and was strongest for the fourth (PM2.5 > 62 μg/m3) compared to the first (PM2.5 < 14 μg/m3) quartiles (OR = 1.36, 95% CI: 1.10, 1.69). Similar non-linear patterns were observed for systolic BP (β = 2.15 mmHg, 95% CI: -0.59, 4.89) and diastolic BP (β = 1.35, 95% CI: -0.20, 2.89), while there was no overall increase in ORs across the full exposure distribution. Individuals who used solid fuels for cooking had lower BP measures compared to clean fuel users (e.g. 34% of solid fuels users compared to 42% of clean fuel users had hypertension), and even in fully adjusted models had slightly decreased odds of hypertension (OR = 0.93; 95% CI: 0.88, 0.99) and reductions in systolic (-0.51 mmHg; 95% CI: -0.99, -0.03) and diastolic (-0.46 mmHg; 95% CI: -0.75, -0.18) BP. In this large international multi-center study, chronic exposures to outdoor PM2.5 was associated with increased BP and hypertension while there were small inverse associations with HAP.


Brain activity associated with dual-task management differs depending on the combinations of response modalities.
Several functional imaging studies have demonstrated the importance of fronto-parietal network in dual-task management. However, neural correlates underlying the difference in intensity of dual-task interference between the same and different response modalities remain unknown. Therefore, we investigated the relationship between brain activity associated with dual-task management and the combinations of response modalities. We used the dual-task requiring bilateral finger responses (DT-same condition) and that requiring finger and oral responses (DT-different condition) to visual and auditory stimuli. The right premotor cortex, precuneus and right posterior parietal cortex were significantly activated in the DT-same condition. The neural activities in the right premotor cortex significantly correlated to the delayed responses in the DT-same condition relative to the single-task conditions, indicating that the right premotor cortex is partly associated with dual-task management (i.e., the regulation of information flow). In addition, neural activity in this brain region was significantly higher in the DT-same condition than in the DT-different condition, suggesting that the difference in intensity between the same and different response modalities is partly associated with difference in the load on the premotor cortex between the DT-same and DT-different conditions. The significant activation of the parietal cortex also differed between the DT-same and DT-different conditions. These results demonstrate that brain activity associated with dual-task management differs depending on the combination of response modalities and that such a difference in brain activity, particularly in the right premotor cortex, might be partly associated with the difference in intensity of dual-task interference between the DT-same and DT-different conditions.


Structural heterogeneity of the C3b/C4b receptor (Cr 1) on human peripheral blood cells.
In these studies CR 1 polymorphism previously demonstrated on erythrocytes (E) was also found on CR 1-bearing peripheral blood leukocytes including polymorphonuclear (PMN), eosinophils, monocytes, and B lymphocytes. However several cell-specific differences in CR1 were found: (a) an approximately 5,000-dalton increase in CR 1 on PMN and eosinophils, (b) unequal band intensity among heterozygotes suggests that there is preferential expression of 220,000- or 225,000-dalton receptors on leukocytes compared to E, and (c) "minor" bands, approximately 15,000 daltons larger than the major receptor molecule, were found on E but not on leukocytes. These observations constitute a unique example of heterogeneity of an integral membrane receptor.


Control and prevention of tuberculosis in Britain: an updated code of practice. Subcommittee of the Joint Tuberculosis Committee of the British Thoracic Society.
A subcommitte was appointed by the Joint Tuberculosis Committee of the British Thoracic Society to review and bring up to date guidelines on control measures for tuberculosis. The updated code of practice emphasises that all cases of tuberculosis must be notified. A minority of patients need admission, and those with positive sputum smears should be regarded as infectious until they have received two weeks of chemotherapy. NHS staff at risk should be protected, and evidence of infectious tuberculosis should be sought as routine among certain prospective NHS employees, schoolteachers, and others. Contact tracing should be vigorously pursued, and all entrants to Britain from countries where tuberculosis is common should be screened. BCG vaccination should be offered in selected instances, and local organisation of tuberculosis services should be extended.


Motivation of health surveillance assistants in Malawi: A qualitative study.
Motivation of health workers is a critical component of performance and is shaped by multiple factors. This study explored factors that influence motivation of health surveillance assistants (HSAs) in Malawi, with the aim of identifying interventions that can be applied to enhance motivation and performance of HSAs. A qualitative study capturing the perspectives of purposively selected participants was conducted in two districts: Salima and Mchinji. Participants included HSAs, health managers, and various community members. Data were collected through focus group discussions (n = 16) and in-depth interviews (n = 44). The study sample was comprised of 112 women and 65 men. Qualitative data analysis was informed by existing frameworks on factors influencing health worker motivation. Our analysis identified five key themes shaping HSA motivation: salary, accommodation, human resource management, supplies and logistics, and community links. Each of these played out at different levels-individual, family, community, and organisational-with either positive or negative effects. Demotivating factors related primarily to the organisational level, while motivating factors were more often related to individual, family, and community levels. A lack of financial incentives and shortages of basic supplies and materials were key factors demotivating HSAs. Supervision was generally perceived as unsupportive, uncoordinated, and top-down. Most HSAs complained of heavy workload. Many HSAs felt further recognition and support from the Ministry of Health, and the development of a clear career pathway would improve their motivation. Factors shaping motivation of HSAs are complex and multilayered; experiences at one level will impact other levels. Interventions are required to enhance HSA motivation, including strengthening the supervision system, developing career progression pathways, and ensuring clear and transparent incentives. HSAs have unique experiences, and there is need to hear and address these to better enable HSAs to cope with the challenging conditions they work in.


Hyperthermia and radiotherapy with or without chemotherapy in locally advanced cervical cancer: a systematic review with conventional and network meta-analyses.
A systematic review with conventional and network meta-analyses (NMA) was conducted to examine the outcomes of loco-regional hyperthermia (HT) with radiotherapy (RT) and/or chemotherapy (CT) in locally advanced cervix cancer, IIB-IVA (LACC). A total of 217 abstracts were screened from five databases and reported as per PRISMA guidelines. Only randomised trials with HT and RT ± CT were considered. The outcomes evaluated were complete response (CR), long-term loco-regional control (LRC), patients alive, acute and late grade III/IV toxicities. Eight articles were finally retained. Six randomised trials with HTRT (n = 215) vs. RT (n = 212) were subjected to meta-analysis. The risk difference for achieving CR and LRC was greater by 22% (p < .001) and 23% (p < .001), respectively, with HTRT compared to RT. A non-significant survival advantage of 8.4% with HTRT was noted with no differences in acute or late toxicities. The only HTCTRT vs. RT trial documented a CR of 83.3% vs. 46.7% (risk difference: 36.7%, p = .001). No other end points were reported. Bayesian NMA, incorporating 13 studies (n = 1000 patients) for CR and 12 studies for patients alive (n = 807 patients), comparing HTCTRT, HTRT, CTRT and RT alone, was conducted. The pairwise comparison of various groups showed that HTRTCT was the best option for both CR and patient survival. This was also evident on ranking treatment modalities based on the "surface under cumulative ranking" values. In LACC, HTRT demonstrates a therapeutic advantage over RT without significant acute or late morbidities. On NMA, HTCTRT appears promising, but needs further confirmation through prospective randomised trials.


Faculty Vitality in Osteopathic Medical Schools: A Pilot Study.
Faculty vitality is defined as the synergy between high levels of satisfaction, productivity, and engagement that enables faculty members to maximize their professional success and achieve goals in concert with institutional goals. Many studies have examined faculty development efforts with regard to satisfaction, retention, or vitality, but, to the authors' knowledge, they have all been conducted in allopathic medical schools and academic health centers. To examine faculty vitality in osteopathic medical schools and address contributors to productivity, engagement, and career satisfaction. This multi-institutional exploratory survey-based study included faculty members from 4 osteopathic medical schools. Surveys with items related to productivity, engagement, career satisfaction, primary department climate and leadership, professional development, and career and life management were sent to faculty members at the 4 participating schools. Most item responses were ranked on Likert-type scales, ranging from 1 (low) to 5 (high). Open-ended questions that explored the participants' experience at their college, factors outside the institution that may affect vitality, and perceived faculty development needs were included at the end of the survey. The overall vitality index was calculated by taking the average of the 3 vitality indicator scores (ie, productivity, engagement, and career satisfaction). Of 236 potential participants, 105 returned the survey for analysis. The mean overall faculty vitality index was 3.2 (range, 1-5). Regarding the 3 contributors to faculty vitality, the mean productivity score was 2.3; professional engagement, 3.5; and career satisfaction, 3.7. Primary department climate and leadership was a significant predictor of faculty vitality (P=.001). The influence of individual vitality factors did not differ between basic science and clinical faculty members. Open-ended questions generated the following themes related to faculty vitality: leadership support, organizational climate, collegiality and value, workload, research funding climate, and family/home life. Participants listed a variety of faculty development needs in the areas of teaching, research, leadership, and professional development. The results of this study suggest that career satisfaction is a significant contributor to vitality in osteopathic medical school faculty members. Additionally, primary department climate and leadership is a significant predictor of faculty vitality. Responses to the open-ended questions further elucidated extrinsic factors that positively and negatively affect vitality, including family and home life and dwindling funding from national medical research agencies. Faculty development efforts should be directed toward enhancing contributors to vitality.


Immunohistochemical Expression of E- and N-Cadherin in Nodular Prostatic Hyperplasia and Prostatic Carcinoma.
Different theories have been postulated to explain the development of nodular prostatic hyperplasia (NPH). Epithelial to mesenchymal transition (EMT) is a physiologic process in which the epithelial cells lose their polarity and cell-cell adhesion and acquire a mesenchymal phenotype. The aim of the present study is to investigate the potential role of E- and N-cadherin in the induction of EMT in NPH and prostatic carcinoma. This study was carried out on 55 cases of NPH and 20 cases prostatic carcinoma for evaluation of immunohistochemical expression of E and N cadherins. Most NPH (54/55 cases, 98.2%) and all cases of prostatic carcinoma showed positive N-cadherin expression in prostatic glands and stroma. High percentage of N-cadherin expression by stromal cells was significantly in favor of prostatic carcinoma compared to NPH. High percentage of N-cadherin expression by epithelial cells of carcinoma group was significantly associated with young age while its high expression by stromal cells was significantly associated with multicentricity. About 96.4% of NPH and 75% of prostatic carcinoma showed positive E-cadherin expression with a significant difference. No significant association between E-cadherin and N-cadherins in both NPH and prostatic carcinoma was identified. The prominent expression of N-cadherin in large numbers of NPH and prostate carcinoma cases in the epithelial and stromal components could point to the occurrence of EMT in those diseases. It also opens a new gate for treatment of those patients by targeting N-cadherin molecule. The absence of inverse association between E-cadherin and N-cadherins in NPH and prostatic carcinoma may indicate that cadherin switch is not an essential step for the development of EMT.


Golden Rice--five years on the road--five years to go?
Provitamin A accumulates in the grain of Golden Rice as a result of genetic transformation. In developing countries, where vitamin A deficiency prevails, grain from Golden Rice is expected to provide this important micronutrient sustainably through agriculture. Since its original production, the prototype Golden Rice has undergone intense research to increase the provitamin A content, to establish the scientific basis for its carotenoid complement, and to better comply with regulatory requirements. Today, the current focus is on how to get Golden Rice effectively into the hands of farmers, which is a novel avenue for public sector research, carried out with the aid of international research consortia. Additional new research is underway to further increase the nutritional value of Golden Rice.


Integrating genetic, transcriptional, and functional analyses to identify 5 novel genes for atrial fibrillation.
Atrial fibrillation (AF) affects >30 million individuals worldwide and is associated with an increased risk of stroke, heart failure, and death. AF is highly heritable, yet the genetic basis for the arrhythmia remains incompletely understood. To identify new AF-related genes, we used a multifaceted approach, combining large-scale genotyping in 2 ethnically distinct populations, cis-eQTL (expression quantitative trait loci) mapping, and functional validation. Four novel loci were identified in individuals of European descent near the genes NEURL (rs12415501; relative risk [RR]=1.18; 95% confidence interval [CI], 1.13-1.23; P=6.5×10(-16)), GJA1 (rs13216675; RR=1.10; 95% CI, 1.06-1.14; P=2.2×10(-8)), TBX5 (rs10507248; RR=1.12; 95% CI, 1.08-1.16; P=5.7×10(-11)), and CAND2 (rs4642101; RR=1.10; 95% CI, 1.06-1.14; P=9.8×10(-9)). In Japanese, novel loci were identified near NEURL (rs6584555; RR=1.32; 95% CI, 1.26-1.39; P=2.0×10(-25)) and CUX2 (rs6490029; RR=1.12; 95% CI, 1.08-1.16; P=3.9×10(-9)). The top single-nucleotide polymorphisms or their proxies were identified as cis-eQTLs for the genes CAND2 (P=2.6×10(-19)), GJA1 (P=2.66×10(-6)), and TBX5 (P=1.36×10(-5)). Knockdown of the zebrafish orthologs of NEURL and CAND2 resulted in prolongation of the atrial action potential duration (17% and 45%, respectively). We have identified 5 novel loci for AF. Our results expand the diversity of genetic pathways implicated in AF and provide novel molecular targets for future biological and pharmacological investigation.


Role of Gonococcal Neisserial Surface Protein A (NspA) in Serum Resistance and Comparison of Its Factor H Binding Properties with Those of Its Meningococcal Counterpart.
Neisseria gonorrhoeae, the causative agent of gonorrhea, has evolved several mechanisms to subvert complement, including binding of the complement inhibitor factor H (FH). We previously reported FH binding to N. gonorrhoeae independently of lipooligosaccharide (LOS) sialylation. Here we report that factor H-like protein 1 (FHL-1), which contains FH domains 1 through 7 and possesses complement-inhibitory activity, also binds to N. gonorrhoeae The ligand for both FH and FHL-1 was identified as neisserial surface protein A (NspA), which has previously been identified as a ligand for these molecules on Neisseria meningitidis As with N. meningitidis NspA (Nm-NspA), N. gonorrhoeae NspA (Ng-NspA) bound FH/FHL-1 through FH domains 6 and 7. Binding of FH/FHL-1 to NspA was human specific; the histidine (H) at position 337 of domain 6 contributed to human-specific FH binding to both Ng- and Nm-NspA. FH/FHL-1 bound Nm-NspA better than Ng-NspA; introducing Q at position 73 (loop 2, present in Ng-NspA) or replacing V and D at positions 112 and 113 in Nm-NspA loop 3 with A and H (Ng-NspA), respectively, reduced FH/FHL-1 binding. The converse Ng-NspA to Nm-NspA mutations increased FH/FHL-1 binding. Binding of FH/FHL-1 through domains 6 and 7 to N. gonorrhoeae increased with truncation of the heptose I (HepI) chain of LOS and decreased with LOS sialylation. Loss of NspA significantly decreased serum resistance of N. gonorrhoeae with either wild-type or truncated LOS. This report highlights the role for NspA in enabling N. gonorrhoeae to subvert complement despite LOS phase variation. Knowledge of FH-NspA interactions will inform the design of vaccines and immunotherapies against the global threat of multidrug-resistant gonorrhea.


Label-free optical imaging technologies for rapid translation and use during intraoperative surgical and tumor margin assessment.
The biannual International Conference on Biophotonics was recently held on April 30 to May 1, 2017, in Fremantle, Western Australia. This continuing conference series brought together key opinion leaders in biophotonics to present their latest results and, importantly, to participate in discussions on the future of the field and what opportunities exist when we collectively work together for using biophotonics for biological discovery and medical applications. One session in this conference, entitled "Tumor Margin Identification: Critiquing Technologies," challenged invited speakers and attendees to review and critique representative label-free optical imaging technologies and their application for intraoperative assessment and guidance in surgical oncology. We are pleased to share a summary in this outlook paper, with the intent to motivate more research inquiry and investigations, to challenge these and other optical imaging modalities to evaluate and improve performance, to spur translation and adoption, and ultimately, to improve the care and outcomes of patients.


Learning styles of medical students, general surgery residents, and general surgeons: implications for surgical education.
Surgical education is evolving under the dual pressures of an enlarging body of knowledge required during residency and mounting work-hour restrictions. Changes in surgical residency training need to be based on available educational models and research to ensure successful training of surgeons. Experiential learning theory, developed by David Kolb, demonstrates the importance of individual learning styles in improving learning. This study helps elucidate the way in which medical students, surgical residents, and surgical faculty learn. The Kolb Learning Style Inventory, which divides individual learning styles into Accommodating, Diverging, Converging, and Assimilating categories, was administered to the second year undergraduate medical students, general surgery resident body, and general surgery faculty at the University of Alberta. A total of 241 faculty, residents, and students were surveyed with an overall response rate of 73%. The predominant learning style of the medical students was assimilating and this was statistically significant (p < 0.03) from the converging learning style found in the residents and faculty. The predominant learning styles of the residents and faculty were convergent and accommodative, with no statistically significant differences between the residents and the faculty. We conclude that medical students have a significantly different learning style from general surgical trainees and general surgeons. This has important implications in the education of general surgery residents.


Early graft failure after infrainguinal arterial bypass.
Early graft failure (EGF), defined as failure within 30 days of an index procedure, is a serious complication after infrainguinal arterial bypass. EGF has not been examined by the use of national data since the widespread adoption of percutaneous treatments for arterial occlusive disease. We used data from the American College of Surgeons National Surgical Quality Improvement Program. Patients who underwent infrainguinal arterial bypass from 2005 to 2011 were selected from the American College of Surgeons National Surgical Quality Improvement Program database. The frequency of 30-day EGF was determined. Univariate and multivariate analyses evaluated risk factors for EGF. Of 23,468 patients who underwent open infrainguinal arterial bypass, 1,065 (4.5%) had EGF. Patients who had EGF were more likely to have a prolonged duration of stay (34.8% vs 12.0%, P < .001), greater rates of reoperation (82.1% vs 14.3%, P < .001) and increased 30-day mortality (5.1% vs 2.1%, P < .001). The rate of additional complications in patients who experienced EGF was 42.0%, compared with 25.4% in those who did not have EGF (P < .001). Patients who experienced complications in addition to EGF were more likely to have complications after graft failure (69.5% vs 31.3%). In multivariable analysis, EGF was associated with younger age, female sex, black race, obesity, thrombocytosis, increased international normalized ratio, femoral-to-tibial bypass, prosthetic graft, and emergent operation. The incidence of EGF after open lower extremity arterial bypass has not increased in an era of increased use of percutaneous techniques. Nevertheless, EGF occurs in almost 5% of patients and is strongly associated with additional complications and mortality. Identifying patients at risk for EGF may facilitate modification of contributing factors. Diminishing the incidence of graft occlusion will lead to decreased morbidity and mortality in this cohort of patients.


Echinoderms: an autoradiographic study of assimilation of dissolved organic molecules.
In a holothurian and an ophiuroid, tritiated glucose and glycine in great dilution are removed from seawater by uptake through the skin. Cells differ in their competence to metabolize specific nutrients, an indication that there are specialized cellular responses to exogenous organic molecules. Embryonic ophiuroid tissues have an exceptional capacity for assimilation.


Experimental observation of invariance of spectral degree of coherence with change in bandwidth of light.
An experimental study is conducted to show the effect of the change in bandwidth of light on the spectral degree of coherence at a pair of points in the cross section of a beam. For this purpose a polychromatic source and a monochromator with variable entrance and exit slits were used to produce a variable bandwidth source. The classic Young's interferometer was used to produce an interference pattern. The spectral measurements of the visibility of the interference fringes show that the spectral degree of coherence remains unaffected by the change in the frequency passband of the light.


The safety and efficacy of antitumour necrosis factor-alpha therapy for inflammatory bowel disease in patients post liver transplantation: a case series.
The role of antitumour necrosis factor-alpha (anti-TNF) therapy for inflammatory bowel disease (IBD) among liver transplant recipients is largely unknown given the rarity of this population and the paucity of literature on the subject. To investigate the safety and efficacy of anti-TNF therapy for refractory IBD in the post liver transplant population. The liver transplant database at London Health Sciences Centre was searched to identify adult patients with IBD treated with anti-TNF therapy post transplantation. Six patients (five men, one woman) were identified, aged 28-65. All patients had cadaveric orthotopic liver transplants. Four patients required transplantation due to primary sclerosing cholangitis, one due to autoimmune hepatitis, and one due to biliary atresia. Five patients suffered from Crohn's disease and the remaining patient from indeterminate colitis. All patients were treated with infliximab 5 mg/kg every 8 weeks after undergoing induction at weeks 0, 2 and 6, with the exception of one patient. The duration of infliximab therapy ranged from 8 weeks to 4 years. Four patients treated with infliximab experienced sustained improvement of their IBD symptoms post transplantation, as documented by Harvey-Bradshaw Index scores demonstrating clinical remission. Of the remaining two patients, neither had sustained improvement of their IBD with infliximab or subsequent adalimumab. One patient was diagnosed with systemic lupus erythematosus and another with colorectal adenocarcinoma following anti-TNF therapy. Otherwise, no side effects were attributed to anti-TNF therapy. Based on this case series, anti-TNF therapy appears to be safe and effective for treating refractory IBD in patients post liver transplantation. These patients respond to anti-TNF therapy similar to those who have not been previously transplanted.


Depolarizing action of a red-tide dinoflagellate brevetoxin on axonal membranes.
The neurotoxic actions of T17 , a toxin isolated from the red-tide dinoflagellate Ptychodiscus brevis, on membrane excitability were investigated by the intracellular microelectrode technique on the crayfish giant axons and by the voltage clamp experiments on the squid giant axons. External application of T17 toxin caused a concentration-dependent depolarization, transient repetitive discharges, followed by depression of the action potential leading to a complete block of excitability. The reversibility of the depolarizing action upon washing decreased as the time of toxin treatment was increased. The T17 -induced depolarization was effectively reversed by 0.3 microM tetrodotoxin or 1 mM Na external solution. Pretreatment with tetrodotoxin completely antagonized the T17 depolarizing action. However, upon washing the axon with the normal external solution, depolarization occurred. Pretreatment with either procaine or dibucaine at high doses also offered protection against the depolarization. The toxin action was greatly potentiated by the sea anemone toxin, anthopleurin-A. The voltage clamp experiments showed that T17 toxin affected sodium current only. The activation voltage for sodium current was shifted in the hyperpolarizing direction by more than 35 mV. T17 toxin also greatly depressed the fast inactivation of sodium current. However, there was no significant change in the kinetics of the sodium tail current. These results indicate that T17 toxin depolarizes the membrane by selectively opening sodium channels at fairly negative potentials and by inhibiting the fast sodium inactivation. We also infer that the binding site for T17 toxin is different from those for tetrodotoxin and sea anemone toxin.


Preparation and clinical evaluation of a high viscosity saliva substitute.
Twenty-five xerostomic patients were given an artificial saliva substitute we had prepared. In this study we evaluated its effect, period of relief, frequency of use, taste, smell, colour, aftertaste, consistency and desire for continued use. Improvement in the patients' complaints after use was assessed by means of a Chi-square test. Although the majority of patients were satisfied with the artificial saliva and there was a change for the better in their condition, only the dry mouth complaint showed a statistically significant level of improvement.


Environmental and hormonal regulation of the activity-dormancy cycle in the cambial meristem involves stage-specific modulation of transcriptional and metabolic networks.
We have performed transcript and metabolite profiling of isolated cambial meristem cells of the model tree aspen during the course of their activity-dormancy cycle to better understand the environmental and hormonal regulation of this process in perennial plants. Considerable modulation of cambial transcriptome and metabolome occurs throughout the activity-dormancy cycle. However, in addition to transcription, post-transcriptional control is also an important regulatory mechanism as exemplified by the regulation of cell-cycle genes during the reactivation of cambial cell division in the spring. Genes related to cold hardiness display temporally distinct induction patterns in the autumn which could explain the step-wise development of cold hardiness. Factors other than low temperature regulate the induction of early cold hardiness-related genes whereas abscisic acid (ABA) could potentially regulate the induction of late cold hardiness-related genes in the autumn. Starch breakdown in the autumn appears to be regulated by the 'short day' signal and plays a key role in providing substrates for the production of energy, fatty acids and cryoprotectants. Catabolism of sucrose and fats provides energy during the early stages of reactivation in the spring, whereas the reducing equivalents are generated through activation of the pentose phosphate shunt. Modulation of gibberellin (GA) signaling and biosynthesis could play a key role in the regulation of cambial activity during the activity-dormancy cycle as suggested by the induction of PttRGA which encodes a negative regulator of growth in the autumn and that of a GA-20 oxidase, a key gibberellin biosynthesis gene during reactivation in spring. In summary, our data reveal the dynamics of transcriptional and metabolic networks and identify potential targets of environmental and hormonal signals in the regulation of the activity-dormancy cycle in cambial meristem.


Rs12970134 near MC4R is associated with appetite and beverage intake in overweight and obese children: A family-based association study in Chinese population.
Recent studies indicated that eating behaviors are under genetic influence, and the melanocortin 4 receptor (MC4R) gene polymorphisms can affect the total energy intake and the consumption of fat, protein and carbohydrates. Our study aims at investigating the association of the MC4R polymorphism with appetite and food intake among Chinese children. A family-based association study was conducted among 151 Chinese trios whose offsprings were overweight/obese children aged 9-15 years. The rs12970134 near MC4R was genotyped, and the Children Eating Behavior Questionnaire (CEBQ) and a self-designed questionnaire measuring food intake were performed. The FBAT and PBAT software packages were used. The family-based association analysis showed that there was a significant association between rs12970134 and obesity (Z = 2.449, P = 0.014). After adjusting for age, gender and standardized BMI, rs12970134 was significantly associated with food responsiveness (FR) among children (β'b = 0.077, Pb = 0.028), and with satiety responsiveness (SR) in trios (P = -0.026). The polymorphism was associated with beverage intake (β'b = 0.331, Pb = 0.00016 in children; P = 0.043 in trios), but not significantly associated with vegetable, fruit or meat intake (P>0.050). We further found a significant mediation effect among the rs12970134, FR and beverage intake (b = 0.177, P = 0.047). Our study is the first to report that rs12970134 near MC4R was associated with appetite and beverage intake, and food responsiveness could mediate the effect of rs12970134 on beverage intake in overweight and obese Chinese children population. Further studies are needed to uncover the genetic basis for eating behaviors, which could lead to develop and implement effective interventional strategies early in life.


Genetic counseling and testing for breast-ovarian cancer susceptibility: what do women want?
To assess preferences for the content and process of genetic counseling and testing for breast-ovarian cancer susceptibility among women at high risk for breast cancer. Ninety-eight healthy women who had a family history of breast cancer in at least two first-degree relatives participated in a structured telephone survey that evaluated preferences for type of provider and the content and process of pretest education and posttest genetic counseling. Forty-two percent of women preferred that pretest education be delivered by a genetic counselor, while 22% preferred an oncologist. This preference was positively associated with a desire to discuss psychosocial issues during the session (P = .001). For posttest counseling, 38% of women preferred an oncologist, while 20% preferred a genetic counselor. However, women who desired supportive counseling during this session were significantly more likely to prefer a genetic counselor to an oncologist (P = .02). Fewer women wished to see a primary care physician or gynecologist for pretest education (11%) or posttest counseling (22%). With regard to the counseling process, 82% of women wished to self-refer for genetic counseling, but 63% desired advice and recommendations about whether to be tested. When feasible, the optimal approach may be for oncologists to work with genetic counselors to provide pretest education and medical recommendations. Elicitation of patients' preferences may be useful to determine the level of counseling services needed.


Current and future carbon stocks in coastal wetlands within the Great Barrier Reef catchments.
Australia's Great Barrier Reef (GBR) catchments include some of the world's most intact coastal wetlands comprising diverse mangrove, seagrass and tidal marsh ecosystems. Although these ecosystems are highly efficient at storing carbon in marine sediments, their soil organic carbon (SOC) stocks and the potential changes resulting from climate impacts, including sea level rise are not well understood. For the first time, we estimated SOC stocks and their drivers within the range of coastal wetlands of GBR catchments using boosted regression trees (i.e. a machine learning approach and ensemble method for modelling the relationship between response and explanatory variables) and identified the potential changes in future stocks due to sea level rise. We found levels of SOC stocks of mangrove and seagrass meadows have different drivers, with climatic variables such as temperature, rainfall and solar radiation, showing significant contributions in accounting for variation in SOC stocks in mangroves. In contrast, soil type accounted for most of the variability in seagrass meadows. Total SOC stock in the GBR catchments, including mangroves, seagrass meadows and tidal marshes, is approximately 137 Tg C, which represents 9%-13% of Australia's total SOC stock while encompassing only 4%-6% of the total extent of Australian coastal wetlands. In a global context, this could represent 0.5%-1.4% of global SOC stock. Our study suggests that landward migration due to projected sea level rise has the potential to enhance carbon accumulation with total carbon gains between 0.16 and 0.46 Tg C and provides an opportunity for future restoration to enhance blue carbon.


The efficacy of ventricular pacing with device automaticity in paediatric patients.
To compare pacemaker reprogramming and re-intervention rates in children with AutoCapture (AC) and conventionally (Conv) programmed devices, and to assess reliability of device automaticity. Data of children with AC (group AC, n = 49) and conventionally programmed devices (group Conv, n = 41) were analysed. A total of 1106 outpatient visits and 147 Holter recordings were screened for device reprogramming and invasive re-intervention. At 2 and 5 years, freedom from reprogramming differed significantly between groups (AC: 63/35% vs. Conv: 13/4%; P < 0.0001), whereas freedom from re-intervention was not different (AC: 95/90% vs. Conv: 95/85%; P = 0.26). Mean yearly rate of reprogramming was lower in group AC (AC: 0.67 +/- 0.55 vs. Conv: 1.13 +/- 0.82; P = 0.005). Follow-up duration correlated with a decreasing number of reprogramming per year in group Conv (rho = -0.73, P < 0.001). No ventricular output reprogramming was required in group AC. Holter recordings required 0.07 +/- 0.13 reprogramming per year in group Conv, none in group AC (P < 0.001). Holter-detected lead dysfunction prompted re-intervention in one patient of each group. Estimated freedom from as well as total yearly rate of device reprogramming was favourable for AC-programmed devices. No difference was seen for the incidence of invasive re-interventions. AC ventricular output control was effective. Structured device follow-up and Holter recordings in specific patient groups remain mandatory for all devices in paediatric patients.


Challenges and opportunities in the creation and implementation of cancer-control plans in Africa.
Cancer on the African continent is quickly becoming an overt public health crisis due to an aging population and changes in lifestyle. The World Health Organization (WHO) states that a national cancer-control programme should aim to reduce cancer incidence and mortality and improve quality of life of cancer patients, through a national cancer-control plan (NCCP) that is systematic, equitable and evidence-based. Despite this, only 11 countries in Africa have a current NCCP. Participants in a US National Cancer Institute-supported, multi-year, technical assistance programme for cancer-control planning noted three main opportunities to improve how plans are created and implemented: 1) mobilisation of resources and partners for plan implementation; 2) accurate surveillance data to promote better resourcing of NCCPs; and, 3) sustainable and innovative partnership models to strengthen capacity to implement NCCPs. Most countries in the region face similar challenges in the development and implementation of an NCCP, including inadequate human, technical, and financial resources. Collaborative partnerships increase access to evidence-based cancer-control planning tools, mentoring and technical assistance, and have the potential to bridge the capacity gap and catalyse better implementation of NCCPs. Challenges can be overcome by better leveraging these opportunities to address the gaps that inhibit cancer control in Africa.


Why Are Newborns Brought to the Emergency Department?
Neonatal period is a peculiar life stage. This study aimed to characterize newborns' visits to the emergency department (ED) of a secondary care hospital. Retrospective analysis of infants up to 28 days, who resorted to the ED between January and December of 2014, was performed. The data included newborn and maternal demographic characteristics and characterization of visits in the ED. From 378 newborns' visits in the ED, 77 were excluded because the visits did not meet the inclusion criteria. From the remaining 301 visits, corresponding to 266 newborns, 56 newborns were referred to hospital care by another doctor, and 34 returned to ED in the neonatal period. The majority of newborns were full term (94%), born by vaginal delivery (55.1%), and had an appropriate birth weight for gestational age (94%). The main reasons for ED visits were gastrointestinal symptoms (33.8%), mucocutaneous lesions (21.4%), and jaundice (16.2%). Half (53%) of the newborns' visits were considered nonurgent. Emergency department visits for reasons justifying medical evaluation were higher in those referred by another doctor (P < 0.001). The rate of hospitalization or guidance for consultation was higher in newborns referred by another doctor (P = 0.017), in those whose color attributed by Manchester Triage System was yellow or orange (P = 0.029) and in newborns older than 7 days (P = 0.035). The majority of ED visits is owing to insufficient caretaker knowledge or benign symptoms without necessity of immediate medical evaluation. These results emphasize the need for parents' education by health professionals.


Anti-TNFalpha therapy in rheumatoid arthritis and autoimmunity.
The aim of the study was to evaluate a panel of autoantibodies in patients affected by rheumatoid arthritis (RA) treated with anti-TNFalpha blockers, and to consider a different autoantibody induction effect by infliximab and etanercept; and in addition to evaluate in these cases a relationship between antinuclear antibody (ANA) titre and both C-reactive protein (CRP) and Blys levels. Fifty-four patients (8 men, 46 women, mean age 51.4 years, mean duration of disease 13.6 years) affected by refractory RA were treated with anti-TNFalpha blockers for 12 consecutive months; 43 patients were given infliximab and 11 etanercept. At baseline and every 4 months a panel of autoantibodies consisting of rheumatoid factor, antinuclear, anti-double-stranded DNA, anti-ENA, anti-mitochondrial, anti-thyroid and anti-neutrophil cytoplasmic antibodies (ANCA) was tested. At the same time CRP level was measured. Blys level was determined at baseline and after 1 year in five cases that developed a strong positivity for ANA during infliximab therapy. In 41 cases (95.3%) treated with infliximab, ANA were detected on at least one occasion, and in almost half of these cases the titre was very high, equal to or higher than 1:1.280. On the other hand, patients treated with etanercept presented ANA positivity in a lower percentage of cases and at a low titre. No correlation was found between ANA titre and CRP level; Blys level did not present a constant trend in patients who developed a very high positivity for ANA. Anti-double-stranded DNA, anti-thyroid or ANCA were found only in a few patients, in the absence of a clinical picture indicative of systemic lupus erythematosus, autoimmune thyroiditis or ANCA-associated vasculitis. A different incidence of ANA positivity was found in infliximab- and etanercept-treated RA patients; this finding might be due to the partially different method of inhibition of TNFalpha between the two drugs. Both CRP and Blys do not seem to participate in this phenomenon. Other autoantibodies were detected in a few patients, but no case of onset of new autoimmune disorders was observed.


Cinnamon from the selection of traditional applications to its novel effects on the inhibition of angiogenesis in cancer cells and prevention of Alzheimer's disease, and a series of functions such as antioxidant, anticholesterol, antidiabetes, antibacterial, antifungal, nematicidal, acaracidal, and repellent activities.
The purpose of this article is to use search engines such as PubMed and Scifinder to locate scholarly articles and reports pertaining to Cinnamon ( ròu guì), its novel effects, preparation, analysis, and use in the prevention and treatment of serious illnesses, such as diabetes, cardiovascular diseases, Alzheimer's disease, and cancer. Cinnamon has been used traditionally in food preparations and as an herbal medicine to treat a variety of ailments and their symptoms. Cinnamon is known to have antioxidant, antibacterial, anti-inflammatory, and other therapeutic properties. New studies reaffirm the importance of cinnamon as a spice but also suggest that it may be a natural remedy to treat serious diseases such as type 2 diabetes, chronic digestion problems, cardiovascular diseases, and even cancer and Alzheimer's disease. This article presents a comprehensive analysis of the botanical, chemical, and pharmacological aspects of cinnamon.


Rapid Design of Knowledge-Based Scoring Potentials for Enrichment of Near-Native Geometries in Protein-Protein Docking.
Protein-protein docking protocols aim to predict the structures of protein-protein complexes based on the structure of individual partners. Docking protocols usually include several steps of sampling, clustering, refinement and re-scoring. The scoring step is one of the bottlenecks in the performance of many state-of-the-art protocols. The performance of scoring functions depends on the quality of the generated structures and its coupling to the sampling algorithm. A tool kit, GRADSCOPT (GRid Accelerated Directly SCoring OPTimizing), was designed to allow rapid development and optimization of different knowledge-based scoring potentials for specific objectives in protein-protein docking. Different atomistic and coarse-grained potentials can be created by a grid-accelerated directly scoring dependent Monte-Carlo annealing or by a linear regression optimization. We demonstrate that the scoring functions generated by our approach are similar to or even outperform state-of-the-art scoring functions for predicting near-native solutions. Of additional importance, we find that potentials specifically trained to identify the native bound complex perform rather poorly on identifying acceptable or medium quality (near-native) solutions. In contrast, atomistic long-range contact potentials can increase the average fraction of near-native poses by up to a factor 2.5 in the best scored 1% decoys (compared to existing scoring), emphasizing the need of specific docking potentials for different steps in the docking protocol.


Changing Body Movement Patterns in 9-Year-Old Baseball Pitchers: A Pilot Study.
Arm injuries in throwing athletes continue to increase. Injuries may be due to multiple variables, including inefficient body movement patterns, especially in young baseball throwers. It is unclear whether these patterns can be efficiently altered in this population. To investigate the effect of a novel 21-day throwing program on body movement patterns in youth baseball players using common practical tools. Our hypothesis was that this program would change body movement patterns over a relatively short period. Descriptive laboratory study. Ten 9-year-old baseball athletes were asked to participate in a 21-consecutive day throwing program focused on decreasing inefficiencies. All participants underwent video evaluation from 2 vantage points as well as radar evaluation before and after the programs. Throwing arm humerothoracic and antecubital angles as well as pelvic angles in the frontal view were measured at the time of front (directional) leg heel/toe down (late cocking) for each of 3 pitches. Glove-side humerothoracic angles and back leg minimum popliteal angles were measured from behind for each of 3 additional pitches. Velocity was measured using a radar gun. All angular measurements were performed by a physical therapist blinded to the purposes of the program and study as well as to video chronology. Throwing arm antecubital angle (P = .01) and humerothoracic angle (P = .03) as well as back leg minimum popliteal angle (P = .03) all decreased, with mean decreases of 35°, 10°, and 8°, respectively. Velocity increased with decreased back leg popliteal angles (P = .019); mean velocity increased 2.6 mph (P = .016). Young baseball throwers can quickly retrain their bodies to accomplish different movement patterns. This novel throwing program may have implications for injury prevention and treatment as we identify better baseball-throwing movement patterns.


Activated human NK cells can stimulate resting B cells to secrete immunoglobulin.
In addition to their cytotoxic function, NK cells can either suppress or enhance Ab production. Upon activation, NK cells generally amplify Ig secretion by activated B cells. We now report that activated NK cells prepared from human peripheral blood can induce resting B cells to produce IgM and IgG. This was demonstrated by adding IL-2 or pokeweed mitogen to purified NK cells and B cells. The addition of IL-2-activated NK cells to B cells also had this effect. The responding B cells did not require activation. Moreover, following fractionation of B cells on Percoll gradients, responsive B cells were found in the high density as well as the low density fractions. The NK cell stimulatory effect was a two-step process. The first step induced B cells to respond to soluble mediators and was mediated by unstimulated NK cells, but not CD4 nor CD8 T cells. Physical contact between NK cells and B cells was required, and mAbs to CD11a and CD54 blocked this interaction. The second step was the production of as yet unidentified cytokine(s) by activated NK cells. These direct T cell-independent stimulatory effects of NK cells on B cells may be important in autoimmune and other chronic inflammatory diseases in which the suppressive effects of NK cells may be blocked.


PTX3 genetic variation and dizygotic twinning in the Gambia: could pleiotropy with innate immunity explain common dizygotic twinning in Africa?
Dizygotic (DZ) twinning has a genetic component and is common among sub-Saharan Africans; in The Gambia its frequency is up to 3% of live births. Variation in PTX3, encoding Pentraxin 3, a soluble pattern recognition receptor that plays an important role both in innate immunity and in female fertility, has been associated with resistance to Mycobacterium tuberculosis pulmonary disease and to Pseudomonas aeruginosa infection in cystic fibrosis patients. We tested whether PTX3 variants in Gambian women associate with DZ twinning, by genotyping five PTX3 single nucleotide polymorphisms (SNPs) in 130 sister pairs (96 full sibs and 34 half sibs) who had DZ twins. Two, three and five SNP haplotypes differed in frequency between twinning mothers and those without a history of twinning (from P = 0.006 to 3.03e-06 for two SNP and three SNP haplotypes, respectively). Twinning mothers and West African tuberculosis-controls from a previous study shared several frequent haplotypes. Most importantly, our data are consistent with an independently reported association of PTX3 and female fertility in a sample from Ghana. Taken together, these results indicate that selective pressure on PTX3 variants that affect the innate immune response to infectious agents, could also produce the observed high incidence of DZ twinning in Gambians.


Graphene and graphene oxide induce ROS production in human HaCaT skin keratinocytes: the role of xanthine oxidase and NADH dehydrogenase.
The extraordinary physicochemical properties of graphene-based nanomaterials (GBNs) make them promising tools in nanotechnology and biomedicine. Considering the skin contact as one of the most feasible exposure routes to GBNs, the mechanism of toxicity of two GBNs (few-layer-graphene, FLG, and graphene oxide, GO) towards human HaCaT skin keratinocytes was investigated. Both materials induced a significant mitochondrial membrane depolarization: 72 h cell exposure to 100 μg mL-1 FLG or GO increased mitochondrial depolarization by 44% and 56%, respectively, while the positive control valinomycin (0.1 μg mL-1) increased mitochondrial depolarization by 48%. Since the effect was not prevented by cyclosporine-A, it appears to be unrelated to mitochondrial transition pore opening. By contrast, it seems to be mediated by reactive oxygen species (ROS) production: FLG and GO induced time- and concentration-dependent cellular ROS production, significant already at the concentration of 0.4 μg mL-1 after 24 h exposure. Among a panel of specific inhibitors of the major ROS-producing enzymes, diphenyliodonium, rotenone and allopurinol significantly reverted or even abolished FLG- or GO-induced ROS production. Intriguingly, the same inhibitors also significantly reduced FLG- or GO-induced mitochondrial depolarization and cytotoxicity. This study shows that FLG and GO induce a cytotoxic effect due to a sustained mitochondrial depolarization. This seems to be mediated by a significant cellular ROS production, caused by the activation of flavoprotein-based oxidative enzymes, such as NADH dehydrogenase and xanthine oxidase.


General and oxidative stress responses in Bacillus subtilis: cloning, expression, and mutation of the alkyl hydroperoxide reductase operon.
The AhpC subunit of the Bacillus subtilis alkyl hydroperoxide reductase was identified as a general stress protein induced in response to heat or salt stress or after entry of the organism into the stationary phase. The ahp operon, encoding the two subunits AhpC and AhpF, was cloned and localized between the gntRKPZ operon and the bglA locus. Two-dimensional gel analyses revealed an especially strong induction of AhpC and AhpF in cells subjected to oxidative stress. Transcriptional studies showed a 3- to 4-fold induction of ahp mRNA after heat or salt stress or starvation for glucose and a 20-fold induction by oxidative stress, thus confirming the protein induction data for AhpC and AhpF. Stress induction occurred at a sigmaA-dependent promoter that overlaps with operator sites similar to the per box. Compared with the wild type, the ahpC mutant was resistant to hydrogen peroxide because of the derepression of the peroxide regulon (N. Bsat, L. Chen, and J. D. Helmann, J. Bacteriol. 178:6579-6586, 1996) but more sensitive to cumene hydroperoxide (CHP) during exponential growth. In contrast, stationary-phase wild-type and ahpC mutant cells displayed complete resistance to treatment with 1 mM CHP. Moreover, a sigmaB mutant was found to be extremely sensitive to CHP during vegetative growth and in stationary phase, which indicates that sigmaB-dependent general stress proteins are involved in the protection of cells against oxidative stress.


The application of food safety interventions in primary production of beef and lamb: a review.
The production of safe red meat depends on effective control of pathogenic microorganisms at all stages of the "farm-to-fork" chain. Eight microorganisms have been selected as the focus of the PathogenCombat project: Shiga toxin producing Escherichia coli (STEC), Mycobacterium avium subspecies paratuberculosis (Map), Listeria monocytogenes, Campylobacter jejuni, Penicillium nordicum, invasive variants of Saccharomyces cerevisiae, hepatitis E virus and tick borne encephalitis virus. The need and potential for coordinated control of the selected food-borne pathogens by on-farm interventions is assessed using a decision tree and a review of the relevant scientific literature. Control measures to reduce the carriage of these pathogens in ruminants prior to slaughter are reviewed with reference to the current regulations and guidelines relating to the primary production. From the eight pathogens investigated, two (STEC and Map), are likely to be effectively controlled by interventions at farm level and the applicable interventions are described and discussed. Ruminants are the main reservoir for these two pathogens; hence a reduction of carriage in livestock should directly reduce human exposure through the consumption of beef and lamb.


Defeating feature fatigue.
Consider a coffeemaker that offers 12 drink options, a car with more than 700 features on the dashboard, and a mouse pad that's also a clock, calculator, and FM radio. All are examples of "feature bloat", or "featuritis", the result of an almost irresistible temptation to load products with lots of bells and whistles. The problem is that the more features a product boasts, the harder it is to use. Manufacturers that increase a product's capability--the number of useful functions it can perform--at the expense of its usability are exposing their customers to feature fatigue. The authors have conducted three studies to gain a better understanding of how consumers weigh a product's capability relative to its usability. They found that even though consumers know that products with more features are harder to use, they initially choose high-feature models. They also pile on more features when given the chance to customize a product for their needs. Once consumers have actually worked with a product, however, usability starts to matter more to them than capability. For managers in consumer products companies, these findings present a dilemma: Should they maximize initial sales by designing high-feature models, which consumers consistently choose, or should they limit the number of features in order to enhance the lifetime value of their customers? The authors' analytical model guides companies toward a happy middle ground: maximizing the net present value of the typical customer's profit stream. The authors also advise companies to build simpler products, help consumers learn which products suit their needs, develop products that do one thing very well, and design market research in which consumers use actual products or prototypes.


What determines the temporal changes of species degree and strength in an oceanic island plant-disperser network?
Network models of frugivory and seed dispersal are usually static. To date, most studies on mutualistic networks assert that interaction properties such as species' degree (k) and strength (s) are strongly influenced by species abundances. We evaluated how species' degree and strength change as a function of temporal variation not only in species abundance, but also in species persistence (i.e., phenology length). In a two-year study, we collected community-wide data on seed dispersal by birds and examined the seasonal dynamics of the above-mentioned interaction properties. Our analyses revealed that species abundance is an important predictor for plant strength within a given sub-network. However, our analyses also reveal that species' degree can often be best explained by the length of fruiting phenology (for plants degree) or by the number of fruiting species (for dispersers degree), which are factors that can be decoupled from the relative abundance of the species participating in the network. Moreover, our results suggest that generalist dispersers (when total study period is considered) act as temporal generalists, with degree constrained by the number of plant species displaying fruits in each span. Along with species identity, our findings underscore the need for a temporal perspective, given that seasonality is an inherent property of many mutualistic networks.


Tools for knowledge acquisition within the NeuroScholar system and their application to anatomical tract-tracing data.
Knowledge bases that summarize the published literature provide useful online references for specific areas of systems-level biology that are not otherwise supported by large-scale databases. In the field of neuroanatomy, groups of small focused teams have constructed medium size knowledge bases to summarize the literature describing tract-tracing experiments in several species. Despite years of collation and curation, these databases only provide partial coverage of the available published literature. Given that the scientists reading these papers must all generate the interpretations that would normally be entered into such a system, we attempt here to provide general-purpose annotation tools to make it easy for members of the community to contribute to the task of data collation. In this paper, we describe an open-source, freely available knowledge management system called 'NeuroScholar' that allows straightforward structured markup of the PDF files according to a well-designed schema to capture the essential details of this class of experiment. Although, the example worked through in this paper is quite specific to neuroanatomical connectivity, the design is freely extensible and could conceivably be used to construct local knowledge bases for other experiment types. Knowledge representations of the experiment are also directly linked to the contributing textual fragments from the original research article. Through the use of this system, not only could members of the community contribute to the collation task, but input data can be gathered for automated approaches to permit knowledge acquisition through the use of Natural Language Processing (NLP). We present a functional, working tool to permit users to populate knowledge bases for neuroanatomical connectivity data from the literature through the use of structured questionnaires. This system is open-source, fully functional and available for download from [1].


Demonstration of immunologic memory using serogroup C meningococcal glycoconjugate vaccine.
Studies of glycoconjugate vaccines have traditionally used an immune challenge with a plain polysaccharide vaccine to demonstrate immunologic memory. Plain polysaccharide vaccines are poorly immunogenic in children and can induce subsequent immunologic hyporesponsiveness. We therefore assessed the use of glycoconjugate vaccines as an alternative method of demonstrating immunologic memory. Children immunized with hepatitis B vaccine or serogroup C meningococcal glycoconjugate vaccine (MenCC) at age 2, 3, 4 months received a plain polysaccharide meningococcal serogroup A/C vaccine (MenACP) or MenCC at age 12 months. A post hoc analysis of serum bactericidal activity responses to MenCC assessed whether this differed in MenCC primed and MenCC naive infants. MenCC primed children displayed higher geometric mean serum bactericidal titers than MenCC naive children following MenACP (1518 compared with 30; P = 0.003). A similar difference was seen after a dose of MenCC to toddlers (MenCC primed: 8663, MenCC naive: 710; P < 0.001). The latter comparison became a borderline significance after adjusting for higher pretoddler immunization serum bactericidal geometric mean titers in the MenCC primed group (P = 0.068). Administration of glycoconjugate vaccines provides an important alternative method of demonstrating immunologic memory, avoiding the use of plain polysaccharide vaccines that are potentially deleterious in children. This has implications for the design of all future clinical trials of glycoconjugate vaccines.


Docosahexaenoic acid complexed to human albumin in experimental stroke: neuroprotective efficacy with a wide therapeutic window.
Docosahexaenoic acid (DHA) complexed to human serum albumin (Alb) is neuroprotective after experimental stroke. Here we tested using lower concentrations of albumin as part of the complex to achieve neuroprotection. We found that lower Alb concentrations extend the therapeutic window of protection beyond 5 h after stroke onset. Sprague-Dawley rats were received 2 h middle cerebral artery occlusion (MCAo). The behavior was evaluated on day 1, 2, 3 and 7 after MCAo. In the dose-response study, animals were given either DHA (5mg/kg), Alb (0.63g/kg), DHA-Alb (5mg/kg + 0.32, 0.63 or 1.25 g/kg) or saline, i.v. 3 h after onset of stroke (n=6-8 per group). In the therapeutic window study, DHA-Alb (5mg/kg + 1.25g/kg) was administered i.v. at either 3, 4, 5, 6 or 7 h after onset of stroke (n=7-9 per group). Alb (1.25g/kg) was given at 3 h or 5 h and saline at 3h after onset of reperfusion. Seven days after MCAo, infarct volumes and number of GFAP, ED-1, NeuN, SMI-71 positive cells and vessels were counted. Moderate DHA-Alb doses (0.63 and 1.25 g/kg) improved neurological scores compared to albumin-treated rats on days 1, 2, 3 and 7. All DHA-Alb doses (0.32, 0.63 and 1.25 g/kg) markedly reduced cortical (by 65-70%), striatal (by 52-63%) and total infarct volumes (by 60-64%) compared to native Alb group. In the therapeutic window study DHA-Alb led to improved neurological score and significant reductions of infarct volumes (especially in the cortical or penumbral region), even when treatment was initiated as late as 7 hours after onset of MCAo. The DHA-Alb complex affords high-grade neurobehavioral neuroprotection in focal cerebral ischemia, equaling or exceeding that afforded by native Alb or DHA, at considerably moderate doses. It has a broad therapeutic window extending to 7 h after stroke onset. Taken together, these finding support the potential clinical feasibility of administering DHA-Alb therapy to patients with acute ischemic stroke.


Effects of pomegranate supplementation on exercise performance and post-exercise recovery in healthy adults: a systematic review.
The functional significance of pomegranate (POM) supplementation on physiological responses during and following exercise is currently unclear. This systematic review aimed (i) to evaluate the existing literature assessing the effects of POM supplementation on exercise performance and recovery; exercise-induced muscle damage, oxidative stress, inflammation; and cardiovascular function in healthy adults and (ii) to outline the experimental conditions in which POM supplementation is more or less likely to benefit exercise performance and/or recovery. Multiple electronic databases were used to search for studies examining the effects of POM intake on physiological responses during and/or following exercise in healthy adult. Articles were included in the review if they investigated the effects of an acute or chronic POM supplementation on exercise performance, recovery and/or physiological responses during or following exercise. The existing evidence suggests that POM supplementation has the potential to confer antioxidant and anti-inflammatory effects during and following exercise, to improve cardiovascular responses during exercise, and to enhance endurance and strength performance and post-exercise recovery. However, the beneficial effects of POM supplementation appeared to be less likely when (i) unilateral eccentric exercise was employed, (ii) the POM administered was not rich in polyphenols (<1·69 g/l) and (iii) insufficient time was provided between POM-ingestion and the assessment of physiological responses/performance (≤1 h). The review indicates that POM has the potential to enhance exercise performance and to expedite recovery from intensive exercise. The findings and recommendations from this review may help to optimise POM-supplementation practice in athletes and coaches to potentially improve exercise-performance and post-exercise recovery.


Scholarship by the Clinician-Educator in Emergency Medicine.
Emergency medicine (EM) continues to grow as an academic specialty. Like most specialties, a large number of academic emergency physicians are focused on education of our graduate student learners. For promotion, clinician-educators (CEs) are required to produce scholarly work and disseminate knowledge. Although promotion requirements may vary by institution, scholarly work is a consistent requirement. Due to the clinical constraints of working in the emergency department, the unique interactions emergency physicians have with their learners, and early adoption of alternative teaching methods, EM CEs' scholarly work may not be adequately described in a traditional curriculum vitae. Using a rubric of established domains around the academic work of CEs, this article describes some of the ways EM educators address these domains. The aim of the article is to provide a guide for academic department leadership, CEs, and promotion committees about the unique ways EM has addressed the work of the CE.


Is low health literacy associated with increased emergency department utilization and recidivism?
The objective was to determine whether patients with low health literacy have higher emergency department (ED) utilization and higher ED recidivism than patients with adequate health literacy. The study was conducted at an urban academic ED with more than 95,000 annual visits that is part of a 13-hospital health system, using electronic records that are captured in a central data repository. As part of a larger, cross-sectional, convenience sample study, health literacy testing was performed using the short test of functional health literacy in adults (S-TOFHLA) and standard test thresholds identifying those with inadequate, marginal, and adequate health literacy. The authors collected patients' demographic and clinical data, including items known to affect recidivism. This was a structured electronic record review directed at determining 1) the median number of total ED visits in this health system within a 2-year period and 2) the proportion of patients with each level of health literacy who had return visits within 3, 7, and 14 days of index visits. Descriptive data for demographics and ED returns are reported, stratified by health literacy level. The Mantel-Haenszel chi-square was used to test whether there is an association between health literacy and ED recidivism. A negative binomial multivariable model was performed to examine whether health literacy affects ED use, including variables significant at the 0.1 alpha level on bivariate analysis and retaining those significant at an alpha of 0.05 in the final model. Among 431 patients evaluated, 13.2% had inadequate, 10% had marginal, and 76.3% had adequate health literacy as identified by S-TOFHLA. Patients with inadequate health literacy had higher ED utilization compared to those with adequate health literacy (p = 0.03). Variables retained in the final model included S-TOFHLA score, number of medications, having a personal doctor, being a property owner, race, insurance, age, and simple comorbidity score. During the study period, 118 unique patients each made at least one return ED visit within a 14-day period. The proportion of patients with inadequate health literacy making at least one return visit was higher than that of patients with adequate health literacy at 14 days, but was not significantly higher within 3 or 7 days. In this single-center study, higher utilization of the ED by patients with inadequate health literacy when compared to those with adequate health literacy was observed. Patients with inadequate health literacy made a higher number of return visits at 14 days but not at 3 or 7 days.


Goal-directed fluid therapy using transoesophageal echocardiographic inferior venacaval index in patients with low left ventricular ejection fraction undergoing major cytoreductive surgery: A clinical trial.
This study aims to trans oesophageal echo cardiographically (TOE) measure inferior venacava diameter (IVCD) during inspiration and expiration in poor left ventricular ejection fraction (LVEF) patients undergoing cytoreductive oncosurgery, to ascertain if any correlation exists between, caval index (DeltaIVCD), and stroke volume variation (SVV), and to compare DeltaIVCD-guided versus SVV-guided fluid therapy. In this prospective, parallel group, interventional study, seventy American Society of Anesthesiologists-III patients, aged 30-75 years, weighing 40-90 kg, with LVEF ≤40% undergoing cytoreductive surgery were included and randomised to group-D (DeltaIVCD-guided fluid therapy) and group-S (SVV-guided fluid therapy). Patients with oesophageal lesions were excluded. After standard endotracheal anaesthesia, arterial and internal jugular vein catheters were placed. A TOE probe was inserted in the interventional group-D. Quantification of IVCD respiratory variations was done. Heart rate (HR), arterial oxygen saturation (SPO2), mean arterial pressure, end tidal carbondioxide (EtCO2), central venous pressure, SVV, IVCD, and urine output (UO) were recorded every 30 min. Post-operative arterial blood gas analysis, lung-ultrasound, chest-radiograph, and serum creatinine were done. Pearson's correlation coefficient as measure of strength of linear relationship, calculation of regression equation, and unpaired t-test for normally distributed continuous variables were used. A positive correlation between DeltaIVCD and SVV (r = 0.751) was observed. A regression equation was obtained for SVV (SVV = [0.317 × DeltaIVCD] + 5.877). Serum lactate, estimated glomerular filtration rate, HR, and UO were within normal limits in group-D. There was no pulmonary oedema. DeltaIVCD-guided intravenous fluid therapy is valuable in low LVEF patients where tight fluid control is essential and any fluid overload may precipitate cardiac failure.


The planar parabolic optical antenna.
One of the simplest and most common structures used for directing light in macroscale applications is the parabolic reflector. Parabolic reflectors are ubiquitous in many technologies, from satellite dishes to hand-held flashlights. Today, there is a growing interest in the use of ultracompact metallic structures for manipulating light on the wavelength scale. Significant progress has been made in scaling radiowave antennas to the nanoscale for operation in the visible range, but similar scaling of parabolic reflectors employing ray-optics concepts has not yet been accomplished because of the difficulty in fabricating nanoscale three-dimensional surfaces. Here, we demonstrate that plasmon physics can be employed to realize a resonant elliptical cavity functioning as an essentially planar nanometallic structure that serves as a broadband unidirectional parabolic antenna at optical frequencies.


In Search of the Antimicrobial Potential of Benzimidazole Derivatives.
A broad series of 4,5,6,7-tetrahalogenated benzimidazoles and 4-(1H-benzimidazol-2-yl)-benzene-1,3-diol derivatives was tested against selected bacteria and fungi. For this study three plant pathogens Colletotrichum sp., Fusarium sp., and Sclerotinia sp., as well as Staphylococcus sp., Enterococcus sp., Escherichia sp., Enterobacter sp., Klebsiella spp. , and Candida spp. as human pathogens were used. MIC values and/or area of growth reduction method were applied in order to compare the activity of the synthesized compounds. From the presented set of 22 compounds, only 8, 16, 18 and 19 showed moderate to good inhibition against bacterial strains. Against Candida strains only compound 19 with three hydroxyl substituted benzene moiety presented high inhibition at nystatin level or lower.


Paraquat Induces Cell Death Through Impairing Mitochondrial Membrane Permeability.
Paraquat (PQ) as a Parkinsonian mimetic has been demonstrated to impair dopaminergic (DAergic) neurons and is highly correlated with the etiology of Parkinson's disease (PD) where the death of DAergic neurons has been mainly attributed to impaired mitochondrial functioning. In this study, PQ-induced cytotoxicity focusing on mitochondrial membrane permeability (MMP), which has been implicated to play a part in neurodegeneration, was investigated. Primarily, PQ-induced cytotoxicity and reactive oxygen species (ROS) were inhibited by an inhibitor of NADPH oxidase (NOX), indicating the toxic effect of PQ redox cycling. Further, dibucaine and cyclosporin A which respectively inhibit mitochondrial apoptosis-induced channels (MAC) and mitochondrial permeability transition pores (mPTP) were used and found to prevent PQ-induced mitochondrial dysfunction, such as decreased mitochondrial membrane potential and increased MMP, mitochondrial ROS, and pro-apoptotic factor release. Knockdown of bax and/or bak blocked PQ-induced mitochondrial clusterization of Bax and/or Bak and cytotoxicity, demonstrating the significance of MAC which is composed of Bax and/or Bak. This clusterization coincided with the release of mitochondrial apoptotic factors before there was an increase in inner MMP, indicating that MAC may precede mPTP formation. Besides, NOX inhibitor but not dibucaine attenuated the earlier PQ-induced cytosolic ROS formation or Bax and/or Bak clusterization indicating PQ redox cycling may account for MAC formation. In this model, we have resolved for the first that PQ cytotoxicity through redox cycling may sequentially result in increased outer (MAC) and inner (mPTP) MMP and suggested MMP could be implicated as a therapeutic target in treating neurodegenerative diseases like PD.


Myosin vc interacts with Rab32 and Rab38 proteins and works in the biogenesis and secretion of melanosomes.
Class V myosins are actin-based motors with conserved functions in vesicle and organelle trafficking. Herein we report the discovery of a function for Myosin Vc in melanosome biogenesis as an effector of melanosome-associated Rab GTPases. We isolated Myosin Vc in a yeast two-hybrid screening for proteins that interact with Rab38, a Rab protein involved in the biogenesis of melanosomes and other lysosome-related organelles. Rab38 and its close homolog Rab32 bind to Myosin Vc but not to Myosin Va or Myosin Vb. Binding depends on residues in the switch II region of Rab32 and Rab38 and regions of the Myosin Vc coiled-coil tail domain. Myosin Vc also interacts with Rab7a and Rab8a but not with Rab11, Rab17, and Rab27. Although Myosin Vc is not particularly abundant on pigmented melanosomes, its knockdown in MNT-1 melanocytes caused defects in the trafficking of integral membrane proteins to melanosomes with substantially increased surface expression of Tyrp1, nearly complete loss of Tyrp2, and significant Vamp7 mislocalization. Knockdown of Myosin Vc in MNT-1 cells more than doubled the abundance of pigmented melanosomes but did not change the number of unpigmented melanosomes. Together the data demonstrate a novel role for Myosin Vc in melanosome biogenesis and secretion.