High energy second-harmonic generation of Nd:glass laser radiation with large aperture CsLiB6O10 crystals.
We have demonstrated the generation of a high-energy green laser pulse using large aperture CsLiB6O10 (CLBO) crystals for the first time to our knowledge. A pulsed energy of 25 J at 532-nm was generated using the 1064-nm incident Nd:glass laser radiation with an energy of 34 J. High conversion efficiency of 74 % at intensities of only 370 MW/cm2 was obtained using a two-stage crystal architecture. This result represents the highest green pulse energy ever reported using the CLBO crystals.


Findings from a mobile application-based cohort are consistent with established knowledge of the menstrual cycle, fertile window, and conception.
To investigate the validity of self-reported fertility data generated by a mobile application-based cohort in comparison with data collected by traditional clinical methodologies. Data were collected from July 2013 to July 2018 through a mobile application designed to track fertility. Bayesian hierarchical models were used to assess day-specific pregnancy probabilities. Descriptive statistics were used to estimate differences in day of ovulation and lengths of menstrual phases and to assess changes in the cervix and ovulation-related symptoms drawing closer to the day of ovulation. Not applicable. Data consisted of 225,596 menstrual cycles from 98,903 women. None. Day-specific probabilities of pregnancy, variability in lengths of the follicular and luteal phases, trends in prevalence of symptoms and cervix changes across the fertile window. Analyses were consistent with established clinical knowledge. Probability of conception was highest during the 5 days before and day of ovulation, with the highest probability occurring the day before ovulation. The average cycle length was 29.6 days, and average lengths of the follicular and luteal phases were 15.8 and 13.7 days, respectively. Closer to day of ovulation, women were more likely to report changes in the cervix corresponding to fluid consistency, feel, position, and openness and symptoms associated with ovulation, including pelvic pain, tender breasts, increased sex drive, and cramps. Components of the menstrual cycle and fertile window, when re-evaluated with a mobile application-based cohort, were found to be consistent with established clinical knowledge, suggesting an agreement between traditional and modern data collection methodologies.


ERICA: prevalence of metabolic syndrome in Brazilian adolescents.
OBJECTIVE To determine the prevalence of metabolic syndrome and its components in Brazilian adolescents. METHODS We evaluated 37,504 adolescents who were participants in the Study of Cardiovascular Risks in Adolescents (ERICA), a cross-sectional, school-based, national study. The adolescents, aged from 12 to 17 years, lived in cities with populations greater than 100,000 inhabitants. The sample was stratified and clustered into schools and classes. The criteria set out by the International Diabetes Federation were used to define metabolic syndrome. Prevalences of metabolic syndrome were estimated according to sex, age group, school type and nutritional status. RESULTS Of the 37,504 adolescents who were evaluated: 50.2% were female; 54.3% were aged from 15 to 17 years, and 73.3% were from public schools. The prevalence of metabolic syndrome was 2.6% (95%CI 2.3-2.9), slightly higher in males and in those aged from 15 to 17 years in most macro-regions. The prevalence was the highest in residents from the South macro-region, in the younger female adolescents and in the older male adolescents. The prevalence was higher in public schools (2.8% [95%CI 2.4-3.2]), when compared with private schools (1.9% [95%CI 1.4-2.4]) and higher in obese adolescents when compared with nonobese ones. The most common combinations of components, referring to 3/4 of combinations, were: enlarged waist circumference (WC), low HDL-cholesterol (HDL-c) and high blood pressure; followed by enlarged WC, low HDL-c and high triglycerides; and enlarged WC, low HDL-c, high triglycerides and blood pressure. Low HDL was the second most frequent component, but the highest prevalence of metabolic syndrome (26.8%) was observed in the presence of high triglycerides. CONCLUSIONS ERICA is the first Brazilian nation-wide study to present the prevalence of metabolic syndrome and describe the role of its components. Despite the prevalence of Metabolic Syndrome being low, the high prevalences of some components and participation of others in the syndrome composition shows the importance of early diagnosis of this changes, even if not grouped within the metabolic syndrome.


Enumeration in Alzheimer's disease and other late life psychiatric syndromes.
Previous studies suggest that visual enumeration is spared in normal aging but impaired in abnormal aging (late stage Alzheimer's disease, AD), raising the task's potential as a marker of dementia. Experiment 1 compared speeded enumeration of 1-9 random dots in early stage AD, vascular dementia (VAD), depression, and age-matched controls. Previous deficits were replicated but they were not specific to AD, with the rate of counting larger numerosities similarly slowed relative to controls by both AD and VAD. Determination of subitizing span was complicated by the surprisingly slower enumeration of one than of two items, especially in AD patients. Experiment 2 showed that AD patients' relative difficulty with one item persisted with further practice and extended to the enumeration of targets among distractors. However, it was abolished when pattern recognition was possible (enumerating dots on a die). Although an enumeration test is unlikely to help differentiate early AD from other common dementias, the unexpected pattern of patients' performance challenges current models of enumeration and requires further investigation.


Hypervirulent group A Streptococcus emergence in an acaspular background is associated with marked remodeling of the bacterial cell surface.
Inactivating mutations in the control of virulence two-component regulatory system (covRS) often account for the hypervirulent phenotype in severe, invasive group A streptococcal (GAS) infections. As CovR represses production of the anti-phagocytic hyaluronic acid capsule, high level capsule production is generally considered critical to the hypervirulent phenotype induced by CovRS inactivation. There have recently been large outbreaks of GAS strains lacking capsule, but there are currently no data on the virulence of covRS-mutated, acapsular strains in vivo. We investigated the impact of CovRS inactivation in acapsular serotype M4 strains using a wild-type (M4-SC-1) and a naturally-occurring CovS-inactivated strain (M4-LC-1) that contains an 11bp covS insertion. M4-LC-1 was significantly more virulent in a mouse bacteremia model but caused smaller lesions in a subcutaneous mouse model. Over 10% of the genome showed significantly different transcript levels in M4-LC-1 vs. M4-SC-1 strain. Notably, the Mga regulon and multiple cell surface protein-encoding genes were strongly upregulated-a finding not observed for CovS-inactivated, encapsulated M1 or M3 GAS strains. Consistent with the transcriptomic data, transmission electron microscopy revealed markedly altered cell surface morphology of M4-LC-1 compared to M4-SC-1. Insertional inactivation of covS in M4-SC-1 recapitulated the transcriptome and cell surface morphology. Analysis of the cell surface following CovS-inactivation revealed that the upregulated proteins were part of the Mga regulon. Inactivation of mga in M4-LC-1 reduced transcript levels of multiple cell surface proteins and reversed the cell surface alterations consistent with the effect of CovS inactivation on cell surface composition being mediated by Mga. CovRS-inactivating mutations were detected in 20% of current invasive serotype M4 strains in the United States. Thus, we discovered that hypervirulent M4 GAS strains with covRS mutations can arise in an acapsular background and that such hypervirulence is associated with profound alteration of the cell surface.


Rapid prototyping of an EEG-based brain-computer interface (BCI).
The electroencephalogram (EEG) is modified by motor imagery and can be used by patients with severe motor impairments (e.g., late stage of amyotrophic lateral sclerosis) to communicate with their environment. Such a direct connection between the brain and the computer is known as an EEG-based brain-computer interface (BCI). This paper describes a new type of BCI system that uses rapid prototyping to enable a fast transition of various types of parameter estimation and classification algorithms to real-time implementation and testing. Rapid prototyping is possible by using Matlab, Simulink, and the Real-Time Workshop. It is shown how to automate real-time experiments and perform the interplay between on-line experiments and offline analysis. The system is able to process multiple EEG channels on-line and operates under Windows 95 in real-time on a standard PC without an additional digital signal processor (DSP) board. The BCI can be controlled over the Internet, LAN or modem. This BCI was tested on 3 subjects whose task it was to imagine either left or right hand movement. A classification accuracy between 70% and 95% could be achieved with two EEG channels after some sessions with feedback using an adaptive autoregressive (AAR) model and linear discriminant analysis (LDA).


Functional interrogation of adult hypothalamic neurogenesis with focal radiological inhibition.
The functional characterization of adult-born neurons remains a significant challenge. Approaches to inhibit adult neurogenesis via invasive viral delivery or transgenic animals have potential confounds that make interpretation of results from these studies difficult. New radiological tools are emerging, however, that allow one to noninvasively investigate the function of select groups of adult-born neurons through accurate and precise anatomical targeting in small animals. Focal ionizing radiation inhibits the birth and differentiation of new neurons, and allows targeting of specific neural progenitor regions. In order to illuminate the potential functional role that adult hypothalamic neurogenesis plays in the regulation of physiological processes, we developed a noninvasive focal irradiation technique to selectively inhibit the birth of adult-born neurons in the hypothalamic median eminence. We describe a method for Computer tomography-guided focal irradiation (CFIR) delivery to enable precise and accurate anatomical targeting in small animals. CFIR uses three-dimensional volumetric image guidance for localization and targeting of the radiation dose, minimizes radiation exposure to nontargeted brain regions, and allows for conformal dose distribution with sharp beam boundaries. This protocol allows one to ask questions regarding the function of adult-born neurons, but also opens areas to questions in areas of radiobiology, tumor biology, and immunology. These radiological tools will facilitate the translation of discoveries at the bench to the bedside.


Positive video-assisted thoracoscopic pericardial window management of a right ventricle stab wound with minimally invasive technique.
This is a case report of a successful right ventricle stab wound suture through a video-assisted pericardial thoracoscopic window, avoiding the need of a thoracotomy diminishing its associated risks, morbidity and costs. A 22-year-old patient was admitted to the emergency room with a stab wound on the left side of his chest, the patient showed symptoms of dyspnea and signs of pulmonary hypoventilation on his left lung, a chest tube were placed on the affected side with an improvement on his symptoms. A video-assisted thoracoscopic pericardial window (VATPW) was performed within the next 24 hours to rule out underlying heart wound. A VATPW shows a 1 cm right ventricle wound which was treated through the same portals avoiding a thoracotomy. The left chest tube was removed 48 hours after de procedure and the patient underwent a control echocardiogram, with no abnormalities reported and no symptoms of dyspnea, respiratory distress or palpitation the patient was subsequently discharged. The VATPW is a feasible and safe procedure to rule out underlying heart injury in individualized cases and it provides a minimally invasive treatment option in selected patients avoiding major surgery like thoracotomy or sternotomy and the added morbidity that carry with them.


Spontaneous Coronary Artery Dissection Causing Cardiac Arrest in a Post-Partum Patient - A Case Report.
Spontaneous coronary artery dissection is a rare condition that can precipitate acute coronary syndrome in pregnant and peripartum women. A 32-year-old previously healthy female, 2-weeks post-partum, presented to the emergency department after sudden cardiac arrest. Return of spontaneous circulation was achieved after multiple rounds of resuscitation. Electrocardiogram revealed ST elevations in the anterolateral leads with reciprocal changes. She was taken to the catheterization lab by cardiology and was found to have a dissection of the distal left anterior descending coronary artery. The patient was subsequently treated medically with heparin and antiplatelet therapy, but ultimately died of anoxic encephalopathy. The purpose of this report is to describe the risk factors, presentation, and management of spontaneous coronary artery dissection which can be easily overlooked given its rarity. Spontaneous coronary artery dissection, out-of-hospital cardiac arrest, peri-partum complications.


Interaction of Candida albicans with adherent human peripheral blood mononuclear cells increases C. albicans biofilm formation and results in differential expression of pro- and anti-inflammatory cytokines.
Monocytes and macrophages are the cell types most commonly associated with the innate immune response against Candida albicans infection. Interactions between the host immune system and Candida organisms have been investigated for planktonic Candida cells, but no studies have addressed these interactions in a biofilm environment. In this study, for the first time, we evaluated the ability of C. albicans to form biofilms in the presence or absence of adherent peripheral blood mononuclear cells (PBMCs; enriched for monocytes and macrophages by adherence). Our analyses using scanning electron and confocal scanning laser microscopy showed that the presence of PBMCs enhanced the ability of C. albicans to form biofilms and that the majority of PBMCs were localized to the basal and middle layers of the biofilm. In contrast to the interactions of PBMCs with planktonic C. albicans, where PBMCs phagocytose fungal cells, PBMCs did not appear to phagocytose fungal cells in biofilms. Furthermore, time-lapse laser microscopy revealed dynamic interactions between C. albicans and PBMCs in a biofilm. Additionally, we found that (i) only viable PBMCs influence Candida biofilm formation, (ii) cell surface components of PBMCs did not contribute to the enhancement of C. albicans biofilm, (iii) the biofilm-enhancing effect of PBMCs is mediated by a soluble factor released into the coculture medium of PBMCs with C. albicans, and (iv) supernatant collected from this coculture contained differential levels of pro- and anti-inflammatory cytokines. Our studies provide new insight into the interaction between Candida biofilm and host immune cells and demonstrate that immunocytes may influence the ability of C. albicans to form biofilms.


Simultaneous reduction of particulate matter and NO(x) emissions using 4-way catalyzed filtration systems.
The next generation of diesel emission control devices includes 4-way catalyzed filtration systems (4WCFS) consisting of both NOx and diesel particulate matter (DPM) control. A methodology was developed to simultaneously evaluate the NOx and DPM control performance of miniature 4WCFS made from acicular mullite, an advanced ceramic material (ACM), that were challenged with diesel exhaust. The impact of catalyst loading and substrate porosity on catalytic performance of the NOx trap was evaluated. Simultaneously with NOx measurements, the real-time solid particle filtration performance of catalyst-coated standard and high porosity filters was determined for steady-state and regenerative conditions. The use of high porosity ACM 4-way catalyzed filtration systems reduced NOx by 99% and solid and total particulate matter by 95% when averaged over 10 regeneration cycles. A "regeneration cycle" refers to an oxidizing ("lean") exhaust condition followed by a reducing ("rich") exhaust condition resulting in NOx storage and NOx reduction (i.e., trap "regeneration"), respectively. Standard porosity ACM 4-way catalyzed filtration systems reduced NOx by 60-75% and exhibited 99.9% filtration efficiency. The rich/lean cycling used to regenerate the filter had almost no impact on solid particle filtration efficiency but impacted NOx control. Cycling resulted in the formation of very low concentrations of semivolatile nucleation mode particles for some 4WCFS formulations. Overall, 4WCFS show promise for significantly reducing diesel emissions into the atmosphere in a single control device.


Risk and response adapted therapy following autologous stem cell transplant in patients with newly diagnosed multiple myeloma (RADAR (UK-MRA Myeloma XV Trial): study protocol for a phase II/III randomised controlled trial.
Multiple myeloma is a plasma cell malignancy that accounts for 1%-2% of newly diagnosed cancers.At diagnosis, approximately 20% of patients can be identified, using cytogenetics, to have inferior survival (high-risk). Additionally, standard-risk patients, with detectable disease (minimal residual disease (MRD)-positive) postautologus stem cell transplant (ASCT), fare worse compared with those who do not (MRD-negative). Research is required to determine whether a risk-adapted approach post-ASCT could further improve patient outcomes. RADAR is a UK, multicentre, risk-adapted, response-guided, open-label, randomised controlled trial for transplant-eligible newly diagnosed multiple myeloma patients, using combinations of lenalidomide (R), cyclophosphamide (Cy), bortezomib (Bor), dexamethasone (D) and isatuximab (Isa).Participants receive RCyBorD(x4) induction therapy, followed by high-dose melphalan and ASCT. Post-ASCT, there are three pathways as follows:A phase III discontinuation design to assess de-escalating therapy in standard-risk MRD-negative patients. Participants receive 12 cycles of Isa maintenance. Those who remain MRD-negative are randomised to either continue or stop treatment.A phase II/III multiarm multistage design to test treatment strategies for treatment escalation in standard-risk MRD-positive patients. Participants are randomised to either; R, RBorD(x4) +R, RIsa, or RBorIsaD(x4) + RIsa.A phase II design to assess the activity of intensive treatment strategies in high-risk patients. Participants are randomised to RBorD(x4) +R or RBorIsaD(x4) + RIsa.1400 participants will be registered to allow for 500, 450 and 172 participants in each pathway. Randomisations are equal and treatment is given until disease progression or intolerance. Ethical approval was granted by the London-Central Research Ethics Committee (20/LO/0238) and capacity and capability confirmed by the appropriate local research and development department for each participating centre prior to opening recruitment. Participant informed consent is required before trial registration and reconfirmed post-ASCT. Results will be disseminated by conference presentations and peer-reviewed publications. ISCRTN46841867.


Polysialic acid glycomimetics promote myelination and functional recovery after peripheral nerve injury in mice.
alpha2,8 Polysialic acid (PSA) is a carbohydrate attached to the glycoprotein backbone of the neural cell adhesion molecule (NCAM) and implicated in nervous system development and repair. Here, we investigated whether PSA can improve functional recovery after peripheral nerve lesion in adult mice. We applied a functional PSA mimicking peptide or a control peptide in a polyethylene cuff used to surgically reconnect the severed stumps of the femoral nerve before it bifurcates into the motor and sensory branches. Using video-based motion analysis to monitor motor recovery over a 3 month postoperative period, we observed a better functional outcome in the PSA mimetic-treated than in control mice receiving a control peptide or phosphate buffered saline. Retrograde tracing of regenerated motoneurons and morphometric analyses showed that motoneuron survival, motoneuron soma size and axonal diameters were not affected by treatment with the PSA mimetic. However, remyelination of regenerated axons distal to the injury site was considerably improved by the PSA mimetic indicating that effects on Schwann cells in the denervated nerve may underlie the functional effects seen in motor recovery. In line with this notion was the observation that the PSA mimetic enhanced the elongation of Schwann cell processes and Schwann cell proliferation in vitro, when compared with the control peptide. Moreover, Schwann cell proliferation in vivo was enhanced in both motor and sensory branches of the femoral nerve by application of the PSA mimetic. These effects were likely mediated by NCAM through its interaction with the fibroblast growth factor receptor (FGFR), since they were not observed when the PSA mimetic was applied to NCAM-deficient Schwann cells, and since application of two different FGFR inhibitors reduced process elongation from Schwann cells in vitro. Our results indicate the potential of PSA mimetics as therapeutic agents promoting motor recovery and myelination after peripheral nerve injury.


Occurrence of Amblyomma dissimile on wild crocodylians in southern Mexico.
Ticks are common ectoparasites of amphibians and reptiles but very few reports of such parasites on crocodylians exist worldwide. Herein, we report the first detailed observations of Amblyomma dissimile Koch, 1844 on the 3 crocodylian species present in Mexico, with the first report of tick parasitism on Crocodylus acutus and the second on Caiman crocodilus chiapasius. This is also the first report of A. dissimile in the state of Quintana Roo. Proportions of infested individuals found in this study ranged from 0.51 to 1.96%, suggesting that tick parasitism in crocodylians is likely opportunistic and occurs when individuals leave the water for terrestrial activities. Tick parasitism does not represent a major threat to crocodylians. The increasing habitat destruction/fragmentation and cattle expansion in southeastern Mexico, however, could increase tick populations and trigger tick parasitism and tick-borne diseases in herpetofauna and other vertebrates, including humans. Thus, studies are needed to better understand these relationships.


Smoking among women following heart transplantation: should we be concerned?
The serious detrimental effects of smoking after heart transplantation (HTX) are well established, but data that demonstrate the effects on female HTX recipients are scarce. The purpose of this study was to describe tobacco use, exposure to second hand smoke (ESHS), and health perceptions of female HTX recipients and examine relationships between these variables of interest and demographic and clinical characteristics of women following HTX. Seventy-two women (mean age, 54.3+/-12.7 years; mean time since transplant, 5.5+/-4.5 years) were enrolled from a single HTX center. Demographic and clinical data, tobacco use, ESHS, and health perceptions were obtained through self-report and chart reviews. Tobacco use was verified by measurement of urine cotinine levels. Twenty-four women were nonsmokers before and after HTX. Eighteen (37.5%) of the 48 women who were former smokers before HTX had returned to tobacco abuse. Only 4 of the 18 accurately reported their smoking behaviors. Forty percent of nonsmokers reported ESHS. Tobacco use and ESHS were highest among African American women. Forty percent of the sample perceived their health status as fair-poor; the remaining 60% reported good-excellent health. In a multivariate analysis, current tobacco use (odds ratio [OR], 5.20; confidence interval [CI], 3.83-9.13) and ESHS (OR, 1.82; CI, 1.17-2.82) were independent predictors of lower health perceptions. Although a majority of the female recipients who used tobacco ceased smoking before HTX, a substantial proportion demonstrated recurrent tobacco use after HTX. Our findings suggest the need for aggressive screening and risk factor interventions to promote smoking cessation before and after HTX in this unique population of female HTX recipients.


An insight into the public acceptance of nutrigenomic-based personalised nutrition.
It is predicted that non-communicable diseases will account for over 73 % of global mortality in 2020. Given that the majority of these deaths occur in developed countries such as the UK, and that up to 80 % of chronic disease could be prevented through improvements in diet and lifestyle, it is imperative that dietary guidelines and disease prevention strategies are reviewed in order to improve their efficacy. Since the completion of the human genome project our understanding of complex interactions between environmental factors such as diet and genes has progressed considerably, as has the potential to individualise diets using dietary, phenotypic and genotypic data. Thus, there is an ambition for dietary interventions to move away from population-based guidance towards 'personalised nutrition'. The present paper reviews current evidence for the public acceptance of genetic testing and personalised nutrition in disease prevention. Health and clear consumer benefits have been identified as key motivators in the uptake of genetic testing, with individuals reporting personal experience of disease, such as those with specific symptoms, being more willing to undergo genetic testing for the purpose of personalised nutrition. This greater perceived susceptibility to disease may also improve motivation to change behaviour which is a key barrier in the success of any nutrition intervention. Several consumer concerns have been identified in the literature which should be addressed before the introduction of a nutrigenomic-based personalised nutrition service. Future research should focus on the efficacy and implementation of nutrigenomic-based personalised nutrition.


Inhibition of CLU4A exhibits a cardioprotective role in hypoxia/reoxygenation-induced injury by an ERK-dependent pathway.
CLU4A is identified as a proto-oncogene in various human cancers. CLU4A was reported to be up-regulated in myocardial ischemia/reperfusion injury, but the precise role of CLU4A played in myocardial ischemia/reperfusion injury remains unknown; and the underlying mechanism of CLU4A in myocardial ischemia/reperfusion injury needs to be investigated. CLU4A expression was measured after myocardial ischemia/reperfusion in mice and in H9C2 cells with hypoxia/reoxygenation treatment by q-PCR and western blotting. The cardioprotective effect of CLU4A inhibition was detected by monitoring the cell viability, cell apoptosis, and LDH activity in vitro and in vivo, and examining the infarct size and cardiac function in vivo. The molecular mechanism was further determined by examining the effects of PD98059, a specific inhibitor of the ERK signaling pathways in H9C2 cells with hypoxia/reoxygenation treatment. CLU4A expression was up-regulated after myocardial ischemia/reperfusion in mice and in H9C2 cells with hypoxia/reoxygenation treatment. Inhibition of CLU4A improved the cell viability, restrained the cell apoptosis, and suppressed LDH activity in vitro. Consistently, knockdown of CLU4A reduced the myocardial infarct size and improved cardiac function in vivo. si-CLU4A treatment increased phosphorylated ERK (p-ERK) in vitro, but the protection role of si-CLU4A was abolished by the ERK inhibitor, PD98059. In conclusion, CLU4A expression was up-regulated in myocardial ischemia/reperfusion. Inhibition of CLU4A exhibited a cardioprotective role by an ERK-dependent pathway.


Global Electric Heterogeneity Risk Score for Prediction of Sudden Cardiac Death in the General Population: The Atherosclerosis Risk in Communities (ARIC) and Cardiovascular Health (CHS) Studies.
Asymptomatic individuals account for the majority of sudden cardiac deaths (SCDs). Development of effective, low-cost, and noninvasive SCD risk stratification tools is necessary. Participants from the Atherosclerosis Risk in Communities study and Cardiovascular Health Study (n=20 177; age, 59.3±10.1 years; age range, 44-100 years; 56% female; 77% white) were followed up for 14.0 years (median). Five ECG markers of global electric heterogeneity (GEH; sum absolute QRST integral, spatial QRST angle, spatial ventricular gradient [SVG] magnitude, SVG elevation, and SVG azimuth) were measured on standard 12-lead ECGs. Cox proportional hazards and competing risks models evaluated associations between GEH electrocardiographic parameters and SCD. An SCD competing risks score was derived from demographics, comorbidities, and GEH parameters. SCD incidence was 1.86 per 1000 person-years. After multivariable adjustment, baseline GEH parameters and large increases in GEH parameters over time were independently associated with SCD. Final SCD risk scores included age, sex, race, diabetes mellitus, hypertension, coronary heart disease, stroke, and GEH parameters as continuous variables. When GEH parameters were added to clinical/demographic factors, the C statistic increased from 0.777 to 0.790 (P=0.008), the risk score classified 10-year SCD risk as high (>5%) in 7.2% of participants, 10% of SCD victims were appropriately reclassified into a high-risk category, and only 1.4% of SCD victims were inappropriately reclassified from high to intermediate risk. The net reclassification index was 18.3%. Abnormal electrophysiological substrate quantified by GEH parameters is independently associated with SCD in the general population. The addition of GEH parameters to clinical characteristics improves SCD risk prediction.


Chronic disease relapses: A cross-sectional study of the associated factors and socioeconomic inequalities during the COVID-19 pandemic in Peru.
To investigate the prevalence, associated factors and socioeconomic inequalities in chronic disease relapses (CDR) during 2020 in Peru. A secondary analysis was made of the National Household Survey on Living Conditions and Poverty (ENAHO) 2020. Participants older than 18 years who suffered from a chronic disease and with information about the occurrence of a CDR in the last 4 weeks prior to the survey were included. Adjusted prevalence ratios (aPRs) were estimated to determine the associated factors. Socioeconomic inequality in CDR was estimated using concentration curves (CC) and the Erreygers concentration index (ECI). Data from 38,662 participants were analyzed; the prevalence of CDR in the last 4 weeks prior to the survey was 16.5% (95% CI: 15.8-17.2). Being female (aPR 1.29; 95% CI: 1.21-1.37), with regards to being male; being 30-39 (aPR 1.22; 95% CI: 1.05-1.42), 40-49 (aPR 1.29; 95% CI: 1.12-1.48), 50-59 (aPR 1.60; 95% CI: 1.41-1.82), and 60 years or older (aPR 1.80; 95% CI: 1.58-2.04), compared to 18-29; reaching up to primary (aPR 1.18; 95% CI: 1.07-1.31), or secondary education (aPR 1.13; 95% CI: 1.02-1.24), in contrast to tertiary education; presenting some physical, psychological or cognitive limitation (aPR 1.33; 95% CI: 1.21-1.46), with respect to experiencing no limitations; and being affiliated to a health insurance (aPR 1.18; CI 95%: 1.09-1.29), opposed to not having health insurance; were associated with a higher probability of CDR. Residing in the natural region of the coastal area (aPR 0.83; 95% CI: 0.74-0.92) was associated with a lower probability of relapse compared to residing in the jungle area. In people with limitations and residents of the jungle areas, the prevalence of CDR was concentrated in those with higher per capita spending. Approximately 1 in 6 Peruvians with chronic diseases had a relapse within the last 4 weeks prior to the survey of 2020 and certain geographic and sociodemographic factors were found to be associated with CDR. It was also found that a higher concentration of CDR was observed in the population with the highest per capita spending with some limitations, as well as in residents of the jungle, implying the need for appropriate policy interventions that address CDR with a special focus on these populations.


The anomalies associated with congenital solitary functioning kidney in children.
The aim of this study was to determine the incidence of associated urological and non-urological anomalies as well as the renal outcome in patients with a congenital solitary func-tioning kidney (CSFK). A retrospective review of 30 consecutive cases of CSFK seen at the pediatric renal service at the Jordan University Hospital between 2004 and 2008 was performed. There were 20 males and 10 females, whose ages ranged from five days to 14 years. In 20 patients (67%), the left kidney was absent. Associated anomalies were detected in 23 (77%) of the 30 patients; urological anomalies accounted for 47% (14/30) and non-urological anomalies were found in 19/30 (53%) patients. The latter included anomalies of the ear, nose and throat (ENT) in 9/30 (30%), musculoskeletal system (one with hypermobile joints) in 8/30 (27%), gastrointestinal (GI) in 7/30 (23%), cardiovascular (CV) in 4/30 (13%) and dermatological with epidermolysis bullosa, endocrine (euthyroid goiter) and gynecological (cervical cyst) in one patient each (3%). Proteinuria was seen in 6/30 (20%) and hypertension in 2/30 (7%) patients. Chronic renal failure (CRF) was seen in 6/30 (20%) patients, of whom three had end-stage renal failure (ESRF). CRF was seen mainly in patients with more than two associated urological anomalies. Idiopathic hyperuricosuria was found in five of the six tested patients (83%). In our study, the most common associated anomalies with CSFK were urological. The presence of more than two associated urological anomalies increased the risk of CRF.


"Blind spots" in forensic autopsy: improved detection of retrobulbar hemorrhage and orbital lesions by postmortem computed tomography (PMCT).
The purpose of this study was to correlate the occurrence of retrobulbar hemorrhage (RBH) with mechanism of injury, external signs and autopsy findings to postmortem computed tomography (PMCT). Six-teen subjects presented with RBH and underwent PMCT, external inspection and conventional autopsy. External inspection was evaluated for findings of the bulbs, black eye, raccoon eyes and Battle's sign. Fractures of the viscerocranium, orbital lesions and RBH were evaluated by PMCT. Autopsy and PMCT was evaluated for orbital roof and basilar skull fracture. The leading manner of death was accident with central regulatory failure in cases of RBH (31.25%). Imaging showed a high sensitivity in detection of orbital roof and basilar skull fractures (100%), but was less specific compared to autopsy. Volume of RBH (0.1-2.4ml) correlated positively to the presence of Battle's sign (p<0.06) and the postmortem interval. Ecchymosis on external inspection correlated with RBH. There was a statistical significant correlation between bulbar lesion and RBH. Orbital roof fracture count weakly correlated with the total PMCT derived RBH volume. Maxillary hemosinus correlated to maxillary fractures, but not to RBH. RBH are a specific finding in forensically relevant head trauma. PMCT is an excellent tool in detecting and quantifying morphological trauma findings particularly in the viscerocranium, one of the most relevant "blind spots" of classic autopsy. PMCT was superior in detecting osseous lesions, scrutinizing autopsy as the gold standard.


Bioactive ginger constituents alleviate protein glycation by trapping methylglyoxal.
Considerable evidence suggests that long-term pathological diabetes is a result of the accumulation of tissue macromolecules that have been progressively modified by nonenzymatic glycation of protein. Methylglyoxal (MGO) is a highly reactive endogenous dicarbonyl metabolite derived from multiple sources such as glucose and lipids and is thought to contribute greatly to protein glycation and the formation of advanced glycation end products (AGEs). In this study, we demonstrated for the first time that both [6]-shogaol (6S) and [6]-gingerol (6G), the major active components in ginger, markedly trapped MGO in vitro and consequently formed mono-MGO adducts, 6S-MGO and 6G-MGO, which were purified from the respective chemical reaction and characterized as novel compounds by NMR experiments and LC-MS/MS approaches. We revealed that the α-carbon of the carbonyl group in the side chain of 6S or 6G is the major active site for trapping MGO. We also demonstrated that 6S and 6G could effectively inhibit the formation of MGO-induced AGEs via trapping MGO in a time-dependent manner in the human serum albumin (HSA)-MGO system. Mono-MGO adducts, 6S-MGO and 6G-MGO, were determined to be the major conjugates in 6S- and 6G-treated HSA-MGO assays, respectively, using LC-ESI-MS techniques. These findings showed the potential effects of 6S and 6G on the prevention of protein glycation, suggesting regular consumption of ginger root extract may attenuate the progression of MGO-associated diabetic complications in patients.


NMR structure of free RGS4 reveals an induced conformational change upon binding Galpha.
Heterotrimeric guanine nucleotide-binding proteins (G-proteins) are transducers in many cellular transmembrane signaling systems where regulators of G-protein signaling (RGS) act as attenuators of the G-protein signal cascade by binding to the Galpha subunit of G-proteins (G(i)(alpha)(1)) and increasing the rate of GTP hydrolysis. The high-resolution solution structure of free RGS4 has been determined using two-dimensional and three-dimensional heteronuclear NMR spectroscopy. A total of 30 structures were calculated by means of hybrid distance geometry-simulated annealing using a total of 2871 experimental NMR restraints. The atomic rms distribution about the mean coordinate positions for residues 5-134 for the 30 structures is 0.47 +/- 0.05 A for the backbone atoms, 0. 86 +/- 0.05 A for all atoms, and 0.56 +/- 0.04 A for all atoms excluding disordered side chains. The NMR solution structure of free RGS4 suggests a significant conformational change upon binding G(i)(alpha)(1) as evident by the backbone atomic rms difference of 1. 94 A between the free and bound forms of RGS4. The underlying cause of this structural change is a perturbation in the secondary structure elements in the vicinity of the G(i)(alpha)(1) binding site. A kink in the helix between residues K116-Y119 is more pronounced in the RGS4-G(i)(alpha)(1) X-ray structure relative to the free RGS4 NMR structure, resulting in a reorganization of the packing of the N-terminal and C-terminal helices. The presence of the helical disruption in the RGS4-G(i)(alpha)(1) X-ray structure allows for the formation of a hydrogen-bonding network within the binding pocket for G(i)(alpha)(1) on RGS4, where RGS4 residues D117, S118, and R121 interact with residue T182 from G(i)(alpha)(1). The binding pocket for G(i)(alpha)(1) on RGS4 is larger and more accessible in the free RGS4 NMR structure and does not present the preformed binding site observed in the RGS4-G(i)(alpha)(1) X-ray structure. This observation implies that the successful complex formation between RGS4 and G(i)(alpha)(1) is dependent on both the formation of the bound RGS4 conformation and the proper orientation of T182 from G(i)(alpha)(1). The observed changes for the free RGS4 NMR structure suggest a mechanism for its selectivity for the Galpha-GTP-Mg(2+) complex and a means to facilitate the GTPase cycle.


Family practice clinics. Survey of family practice residents' attitudes.
All residents of McGill University's Department of Family Medicine were surveyed by mail about their family practice clinic experience. Residents were generally satisfied with their training site and their supervision, but noted problems with volume and diversity of patients, learning certain procedures, and knowledge of community resources. They did not want more family medicine clinic time.


Noncanonical NF-κB mediates the Suppressive Effect of Neutrophil Elastase on IL-8/CXCL8 by Inducing NKRF in Human Airway Smooth Muscle.
Neutrophil elastase (NE) suppresses IL-8/CXCL8 in human airway smooth muscle cells (hASM) while stimulating its production in respiratory epithelial cells. This differential effect is mediated by the selective induction of NKRF and dysregulation in chronic inflammatory diseases. We hypothesized that the differential activation of NF-κB subunits confer the opposite effect of NKRF on IL-8/CXCL8 in primary hASM and A549 cells stimulated with NE. The events occurring at the promoters of NKRF and IL-8/CXCL8 were observed by ChIP assays, and the functional role of RelB was confirmed by knockdown and overexpression. Although p65 was stimulated in both cell types, RelB was only activated in NE-treated hASM, as confirmed by NF-κB DNA binding ELISA, Western blotting and confocal microscopy. Knockdown of RelB abolished the induction of NKRF and converted the suppression of IL-8/CXCL8 to stimulation. The forced expression of RelB induced NKRF production in hASM and A549 cells. NE activated the NIK/IKK1/RelB non-canonical NF-κB pathway in hASM but not in A549. The nuclear-translocated RelB was recruited to the NKRF promoter around the putative κB site, accompanied by p52 and RNA polymerase II. In conclusion, NFRF is a novel RelB-response gene, and NE is a stimulator of the non-canonical RelB/NF-κB pathway in hASM.


Genetic and phenotypic characterization of the bla(CMY) gene from Escherichia coli and Salmonella enterica isolated from food-producing animals, humans, the environment, and retail meat.
The bla(CMY-2) family of the ampC beta-lactamase genes confer broad-spectrum resistance to beta-lactam antimicrobials, including ceftriaxone and ceftiofur, as well as to beta-lactamase inhibitors, such as clavulanic acid. Organisms with the bla(CMY-2) phenotype have been recovered from the environment and from retail meat products, posing a potential public health risk. The objectives of this study were to sequence the bla(CMY-2) gene from Escherichia coli and Salmonella enterica from multiple sources that had a reduced susceptibility to ceftriaxone and to determine the effect of observed mutations in the bla(CMY-2) gene on the antimicrobial resistance phenotype (spectrum and minimum inhibitory concentration/susceptibility patterns) of the isolates. The bla(CMY-2) genes from 52 bacterial isolates were sequenced for this study. Sixty-two percent (32/52) were E. coli and 38% (20/52) were S. enterica. Of the 32 E. coli isolates, 30 were found to carry a beta-lactamase gene that was 100% homologous to bla(CMY-2). One of the E. coli isolates was found to contain a gene that was 90% homologous to bla(CMY-2). This isolate also had lower minimum inhibitory concentrations to tetracyclines, streptomycin, and the sulfonamide antimicrobials than are commonly expected for isolates containing the bla(CMY-2). Of the 20 genes obtained from Salmonella isolates, 8 (40%) were found to be homologous to bla(CMY-2), with no altered susceptibility phenotypes observed.


Standardizing nomenclature in regional anesthesia: an ASRA-ESRA Delphi consensus study of abdominal wall, paraspinal, and chest wall blocks.
There is heterogeneity in the names and anatomical descriptions of regional anesthetic techniques. This may have adverse consequences on education, research, and implementation into clinical practice. We aimed to produce standardized nomenclature for abdominal wall, paraspinal, and chest wall regional anesthetic techniques. We conducted an international consensus study involving experts using a three-round Delphi method to produce a list of names and corresponding descriptions of anatomical targets. After long-list formulation by a Steering Committee, the first and second rounds involved anonymous electronic voting and commenting, with the third round involving a virtual round table discussion aiming to achieve consensus on items that had yet to achieve it. Novel names were presented where required for anatomical clarity and harmonization. Strong consensus was defined as ≥75% agreement and weak consensus as 50% to 74% agreement. Sixty expert Collaborators participated in this study. After three rounds and clarification, harmonization, and introduction of novel nomenclature, strong consensus was achieved for the names of 16 block names and weak consensus for four names. For anatomical descriptions, strong consensus was achieved for 19 blocks and weak consensus was achieved for one approach. Several areas requiring further research were identified. Harmonization and standardization of nomenclature may improve education, research, and ultimately patient care. We present the first international consensus on nomenclature and anatomical descriptions of blocks of the abdominal wall, chest wall, and paraspinal blocks. We recommend using the consensus results in academic and clinical practice.


Perception of the importance of chemistry research papers and comparison to citation rates.
Chemistry researchers are frequently evaluated on the perceived significance of their work with the citation count as the most commonly-used metric for gauging this property. Recent studies have called for a broader evaluation of significance that includes more nuanced bibliometrics as well as altmetrics to more completely evaluate scientific research. To better understand the relationship between metrics and peer judgements of significance in chemistry, we have conducted a survey of chemists to investigate their perceptions of previously published research. Focusing on a specific issue of the Journal of the American Chemical Society published in 2003, respondents were asked to select which articles they thought best matched importance and significance given several contexts: highest number of citations, most significant (subjectively defined), most likely to share among chemists, and most likely to share with a broader audience. The answers to the survey can be summed up in several observations. The ability of respondents to predict the citation counts of established research is markedly lower than the ability of those counts to be predicted by the h-index of the corresponding author of each article. This observation is conserved even when only considering responses from chemists whose expertise falls within the subdiscipline that best describes the work performed in an article. Respondents view both cited papers and significant papers differently than papers that should be shared with chemists. We conclude from our results that peer judgements of importance and significance differ from metrics-based measurements, and that chemists should work with bibliometricians to develop metrics that better capture the nuance of opinions on the importance of a given piece of research.


Near-infrared 808 nm light boosts complex IV-dependent respiration and rescues a Parkinson-related pink1 model.
Mitochondrial electron transport chain (ETC) defects are observed in Parkinson's disease (PD) patients and in PD fly- and mouse-models; however it remains to be tested if acute improvement of ETC function alleviates PD-relevant defects. We tested the hypothesis that 808 nm infrared light that effectively penetrates tissues rescues pink1 mutants. We show that irradiating isolated fly or mouse mitochondria with 808 nm light that is absorbed by ETC-Complex IV acutely improves Complex IV-dependent oxygen consumption and ATP production, a feature that is wavelength-specific. Irradiating Drosophila pink1 mutants using a single dose of 808 nm light results in a rescue of major systemic and mitochondrial defects. Time-course experiments indicate mitochondrial membrane potential defects are rescued prior to mitochondrial morphological defects, also in dopaminergic neurons, suggesting mitochondrial functional defects precede mitochondrial swelling. Thus, our data indicate that improvement of mitochondrial function using infrared light stimulation is a viable strategy to alleviate pink1-related defects.


FOXP3 infiltrating lymphocyte density and PD-L1 expression in operable non-small cell lung carcinoma.
Purpose/Aim: Regulatory FOXP3+ T-cells control the cytotoxic activity of effector cells and may have an essential role in the development of immune tolerance in cancer patients. Programed death ligand 1 PD-L1, expressed on cancer cell membranes also blocks the cytotoxic activity of PD1+ cytotoxic lymphocytes. Materials and Methods: We assessed the immunohistochemical detection of these immune-tolerance related markers in a series of 98 non-small cell lung carcinomas (NSCLC) treated with surgery. The Tumor Infiltration Lymphocyte TIL density (mean number per x400 optical field) and the percentage of FOXP3+ TILs were assessed. Results: PD-L1 expression was directly linked with the TIL density (p = 0.01) and with the extent of infiltration with FOXP3+ TILs, named as the FIL-score (p = 0.01). FIL-score was significantly higher in stage I disease (p = 0.04). IL6 expression was linked with high TIL-score. A low TIL-score, characterizing immune deficient tumors defined a significantly poorer prognosis subgroup of patients (p = 0.03). Stratification of these tumors according to the FIL-score showed that FOXP3 expression by TILs correlated with an even a poorer prognosis in univariate (p = 0.007; median survival 14 vs. 44 months, respectively) and in multivariate analysis (p = 0.01, hazard ratio 4.3). Conclusion: Tumor stroma infiltration by FOXP3+ Tregs is an early event in the progression of NSCLC. Low lymphocytic infiltration defines poor prognosis, which becomes worse when the small numbers of infiltrating lymphocytes characterizing these tumors contain FOXP3 + Tregs. Furthermore, the direct association of FOXP3+ Treg infiltration density with PD-L1 expression by cancer cells implies a co-ordinated immune-suppressive activity in NSCLC.


Managing peatland vegetation for drinking water treatment.
Peatland ecosystem services include drinking water provision, flood mitigation, habitat provision and carbon sequestration. Dissolved organic carbon (DOC) removal is a key treatment process for the supply of potable water downstream from peat-dominated catchments. A transition from peat-forming Sphagnum moss to vascular plants has been observed in peatlands degraded by (a) land management, (b) atmospheric deposition and (c) climate change. Here within we show that the presence of vascular plants with higher annual above-ground biomass production leads to a seasonal addition of labile plant material into the peatland ecosystem as litter recalcitrance is lower. The net effect will be a smaller litter carbon pool due to higher rates of decomposition, and a greater seasonal pattern of DOC flux. Conventional water treatment involving coagulation-flocculation-sedimentation may be impeded by vascular plant-derived DOC. It has been shown that vascular plant-derived DOC is more difficult to remove via these methods than DOC derived from Sphagnum, whilst also being less susceptible to microbial mineralisation before reaching the treatment works. These results provide evidence that practices aimed at re-establishing Sphagnum moss on degraded peatlands could reduce costs and improve efficacy at water treatment works, offering an alternative to 'end-of-pipe' solutions through management of ecosystem service provision.


Quantitative scanning thermal microscopy based on determination of thermal probe dynamic resistance.
Resistive thermal probes used in scanning thermal microscopy provide high spatial resolution of measurement accompanied with high sensitivity to temperature changes. At the same time their sensitivity to variations of thermal conductivity of a sample is relatively low. In typical dc operation mode the static resistance of the thermal probe is measured. It is shown both analytically and experimentally that the sensitivity of measurement can be improved by a factor of three by measuring the dynamic resistance of a dc biased probe superimposed with small ac current. The dynamic resistance can be treated as a complex value. Its amplitude represents the slope of the static voltage-current U-I characteristic for a given I while its phase describes the delay between the measured ac voltage and applied ac current component in the probe. The phase signal also reveals dependence on the sample thermal conductivity. Signal changes are relatively small but very repeatable. In contrast, the difference between dynamic and static resistance has higher sensitivity (the same maximum value as that of the 2nd and 3rd harmonics), and also much higher amplitude than higher harmonics. The proposed dc + ac excitation scheme combines the benefits of dc excitation (mechanical stability of probe-sample contact, average temperature control) with those of ac excitation (base-line stability, rejection of ambient temperature influence, high sensitivity, lock-in signal processing), when the experimental conditions prohibit large ac excitation.


Novel Borrelia burgdorferi isolates from Ixodes scapularis and Ixodes dentatus ticks feeding on humans.
Seven cultures of Borrelia burgdorferi differing from strains B31 and ZS7 were identified from among 99 isolates from Ixodes scapularis ticks and from white-footed mice (Peromyscus leucopus) and 1 isolate from an Ixodes dentatus tick. Five of the six novel isolates from I. scapularis and the isolate from I. dentatus were from ticks feeding on humans. The six isolates from I. scapularis lacked OspA and OspB, four possessed an OspD band, and two reacted with an anti-OspC monoclonal antibody. Restriction fragment length polymorphisms of HindIII-digested DNAs from six OspA-negative isolates did not hybridize with radiolabeled ospA or LA88 DNA, and only isolate 46047 hybridized with the pG gene. Fragments similar to those recorded for the standard B. burgdorferi sensu stricto strains B31 and ZS7 were obtained with the fla and the HSP70 genes. Pulsed-field gel electrophoresis patterns of DNA digested with MluI included the specific B. burgdorferi sensu stricto band at 135 kbp for the five OspA-negative isolates from I. scapularis ticks. The six novel isolates apparently lack the 55-kbp plasmid encoding OspA. The pG-containing plasmid may be missing from all but isolate 46047. The isolate from the I. dentatus tick was similar to previous isolates from I. dentatus ticks feeding on rabbits. None of the isolates could be recovered from inoculated C3H/HeNCrlBR or white-footed mice. All isolates reacted with sera from humans with early or late Lyme disease. Our studies demonstrate that these borreliae occur in ticks feeding on humans, and therefore, at least some humans in the northeastern United States are likely being exposed to borreliae other than the classic B31-type strains that have thus far been isolated from humans.


A systematic examination of the use of online social networking sites for sexual health promotion.
In recent years social networking sites (SNSs) have grown rapidly in popularity. The popularity of these sites, along with their interactive functions, offer a novel environment in which to deliver health promotion messages. The aim of this paper is to examine the extent to which SNSs are currently being used for sexual health promotion and describe the breadth of these activities. We conducted a systematic search of published scientific literature, electronic sources (general and scientific search engines, blogs) and SNSs (Facebook, MySpace) to identify existing sexual health promotion activities using SNSs. Health promotion activities were eligible for inclusion if they related to sexual health or behaviour, utilised one or more SNSs, and involved some element of health promotion. Information regarding the source and type of health promotion activity, target population and site activity were extracted. 178 sexual health promotion activities met the inclusion criteria and were included in the review; only one activity was identified through a traditional systematic search of the published scientific literature. Activities most commonly used one SNS, were conducted by not-for-profit organisations, targeted young people and involved information delivery. Facebook was the most commonly used SNS (used by 71% of all health promotion activities identified), followed by MySpace and Twitter. Seventy nine percent of activities on MySpace were considered inactive as there had been no online posts within the past month, compared to 22% of activities using Facebook and 14% of activities using Twitter. The number of end-users and posts in the last seven days varied greatly between health promotion activities. SNSs are being used for sexual health promotion, although the extent to which they are utilised varies greatly, and the vast majority of activities are unreported in the scientific literature. Future studies should examine the key factors for success among those activities attracting a large and active user base, and how success might be measured, in order to guide the development of future health promotion activities in this emerging setting.


Depression in older people is underdiagnosed.
Depression is more common in old age than dementia yet is underdiagnosed and undertreated. It is important to recognise that patients may not always present in a typical way, features that may indicate depression include anxiety, a preoccupation with somatic symptoms, and a change in function. The presence of understandable triggers and causes should not deter GPs from offering treatment, as long as symptoms are pervasive and continuously persist beyond two weeks. Age-related disabilities and changes to physical health are major risk factors for depression in older people. Vascular diseases, including stroke, MI and diabetes increase the risk of depression, both through direct effects on the brain and the psychological effects. Likewise, dementia is a risk factor for depression. Psychological factors such as loneliness and loss of a valued role, as well as social factors related to retirement, bereavement and reduced independence may also increase the risk. Patients with a previous history of depression and anxiety disorders are at increased risk of depression in later life. Assessment and diagnosis are largely based on a careful history. This should focus on eliciting current features of depression, which have been present for at least two weeks, and are associated with a significant change in function. It is important to exclude organic disorders including anaemia, B12 and folate deficiency, and hypothyroidism that may mimic symptoms of depressive disorder. Referral to specialist mental health services is indicated in the following cases: diagnostic difficulty, poor response to treatment, psychotic symptoms, significant psychiatric comorbidity or a risk of self-neglect or suicide.


Kinases regulating Golgi apparatus structure and function.
Protein kinases control Golgi function in both mitotic and interphase cells. In mitosis, phosphorylation of structural proteins by Cdk1 (cyclin-dependent kinase 1)-cyclin B, Polo-like and mitogen-activated protein kinases underlie changes in Golgi reorganization during cell division. While in interphase, signalling pathways that are associated with the Golgi control secretory function through a variety of mechanisms. Some of these, notably those involving protein kinase D and Ste20 family kinases, are also relevant for the establishment and maintenance of cell polarization and migration.


The half-life of 25(OH)D after UVB exposure depends on gender and vitamin D receptor polymorphism but mainly on the start level.
The 25-hydroxy vitamin D (25(OH)D) production caused by UVB exposure is usually underestimated as the concurrent degradation of 25(OH)D is not considered. Therefore, the decrease in 25(OH)D was investigated during a 7-week period in winter when ambient UVB is negligible. Twenty-two healthy Danish individuals (113 samples) participated and had a mean and steady maximal 25(OH)D start level of 132 nmol l-1 (range of 68-216 nmol l-1) due to long-term UVB treatment prior to this study. In this group with high 25(OH)D start levels, the decrease in 25(OH)D was best described by an exponential model. This suggests a quantitatively larger elimination of 25(OH)D at high 25(OH)D start levels. A linear model (logarithm of 25(OH)D) including personal start levels as intercepts and a slope influenced by gender and the vitamin D receptor gene polymorphism rs2228570 explained 87.8% of the observed variation. The mean half-life was 89 days with a difference in half-life of 120 days between a male with rs2228570 genotype GG (59 days) and a female with rs2228570 genotype AA/AG (179 days). Thus, these two parameters explained a large part of the observed inter-individual variation of 25(OH)D. Furthermore, the decrease was analysed in two groups with medium and low 25(OH)D start levels resulting in longer half-lives of 149 days and 199 days, respectively. The longer half-lives at lower 25(OH)D levels may be caused by storage mobilisation, changed catabolism or increased intestinal absorption.


Parallel profiling of cancer cells and proteins using a graphene oxide functionalized ac-EHD SERS immunoassay.
Circulating biomarkers have emerged as promising non-invasive, real-time surrogates for cancer diagnosis, prognosis and monitoring of the therapeutic response. Current bio-sensing techniques mostly involve detection of either circulating cells or proteins which are inadequate in unfolding complex pathologic transformations. Herein, we report parallel detection of cellular and molecular markers (protein) for cancer using a multiplex platform featuring (i) graphene oxide (GO) functionalization that increases the active surface area and more importantly reduces the functionalization steps for rapid detection, (ii) alternating-current electrohydrodynamic (ac-EHD) fluid flow that provides delicate micro-mixing to enhance target-sensor interactions thereby minimizing non-specific binding and (iii) surface enhanced Raman scattering (SERS) for multiplex detection. We find that our platform possesses high sensitivity for detecting both proteins and cells. More importantly, this platform not only detects the cancer cells but also can simultaneously monitor the heterogeneous expression of cell surface proteins which could be clinically useful to determine effective patient therapy. We demonstrate the specific and sensitive detection of breast cancer cells from a mixture of non-target cells and report the heterogeneous expression of human epidermal growth factor receptor 2 (HER2) proteins on the individual cancer cell surface. Concurrently, we detect as low as 100 fg mL-1 HER2 and Mucin 16 proteins spiked in blood serum.


Gold(i)-catalyzed 6-endo-dig azide-yne cyclization: efficient access to 2H-1,3-oxazines.
Denitrogenative 6-endo-dig azide-yne cyclization of α-propargyloxy-β-haloalkylazides was enabled by gold catalysis, thus providing 2H-1,3-oxazines. This rare cyclization mode in gold-catalyzed reactions of azide-yne substrates was demonstrated to be facilitated and controlled by electronic and resonance effects of the alkyne substituents. Molecular transformations of the as-prepared 2H-1,3-oxazines were also investigated.


Planar Cell Polarity Effector Proteins Inturned and Fuzzy Form a Rab23 GEF Complex.
A subset of Rab GTPases have been implicated in cilium formation in cultured mammalian cells [1-6]. Rab11 and Rab8, together with their GDP-GTP exchange factors (GEFs), TRAPP-II and Rabin8, promote recruitment of the ciliary vesicle to the mother centriole and its subsequent maturation, docking, and fusion with the cell surface [2-5]. Rab23 has been linked to cilium formation and membrane trafficking at mature cilia [1, 7, 8]; however, the identity of the GEF pathway activating Rab23, a member of the Rab7 subfamily of Rabs, remains unclear. Longin-domain-containing complexes have been shown to act as GEFs for Rab7 subfamily GTPases [9-12]. Here, we show that Inturned and Fuzzy, proteins previously implicated as planar cell polarity (PCP) effectors and in developmentally regulated cilium formation [13, 14], contain multiple longin domains characteristic of the Mon1-Ccz1 family of Rab7 GEFs and form a specific Rab23 GEF complex. In flies, loss of Rab23 function gave rise to defects in planar-polarized trichome formation consistent with this biochemical relationship. In cultured human and mouse cells, Inturned and Fuzzy localized to the basal body and proximal region of cilia, and cilium formation was compromised by depletion of either Inturned or Fuzzy. Cilium formation arrested after docking of the ciliary vesicle to the mother centriole but prior to axoneme elongation and fusion of the ciliary vesicle and plasma membrane. These findings extend the family of longin domain GEFs and define a molecular activity linking Rab23-regulated membrane traffic to cilia and planar cell polarity.


Enhanced Rate of Acquisition of Point Mutations in Mouse Intestinal Adenomas Compared to Normal Tissue.
The most prevalent single-nucleotide substitution (SNS) found in cancers is a C-to-T substitution in the CpG motif. It has been proposed that many of these SNSs arise during organismal aging, prior to transformation of a normal cell into a precancerous/cancer cell. Here, we isolated single intestinal crypts derived from normal tissue or from adenomas of Apcmin/+ mice, expanded them minimally in vitro as organoids, and performed exome sequencing to identify point mutations that had been acquired in vivo at the single-cell level. SNSs, most of them being CpG-to-TpG substitutions, were at least ten times more frequent in adenoma than normal cells. Thus, contrary to the view that substitutions of this type are present due to normal-cell aging, the acquisition of point mutations increases upon transformation of a normal intestinal cell into a precancerous cell.


Sphaerodoridae (Annelida) of the deep Northwestern Atlantic, including remarkable new species of Euritmia and Sphaerephesia.
Sphaerodoridae (Annelida) is a seeming uncommon and minimally diverse group of polychaetes in the northwestern Atlantic, with only seven species reported from the United States, and none from the eastern coast of Canada, before the present study. Review of the large Smithsonian collection (National Museum of Natural History, Washington) revealed the presence of two morphologically extraordinary undescribed species and added a new record to the north-western Atlantic region. Euritmia carolensis sp. n. is characterised by bearing approximately 20 sessile spherical papillae arranged in three transverse rows per segment, ventrum with 4-6 larger papillae near the parapodial bases and parapodia without papillae; bearing 4-5 simple chaetae that are enlarged subdistally. Sphaerephesia amphorata sp. n. is distinguished from other congeners in the presence of four longitudinal rows of sessile, bottle-shaped macrotubercles with exceptionally long digitiform terminal papilla, and parapodia with four rounded and small papillae, bearing 4-7 compound chaetae, with blades 7-11 times as long as wide. Other encountered species are also herein re-described, including intraspecific variation and updated iconography. Comparison of material also allowed some systematic changes in the group, including the synonymisation of the genus Amacrodorum with Euritmia, and the transfer of Ephesiopsis shivae to Ephesiella. A key to the species reported from the Northwestern Atlantic is provided.


New Modalities for the Administration of Inhaled Nitric Oxide in Intensive Care Units After Cardiac Surgery or for Neonatal Indications: A Prospective Observational Study.
Nitric oxide (NO) has a well-known efficacy in pulmonary hypertension (PH), with wide use for 20 years in many countries. The objective of this study was to describe the current use of NO in real life and the gap with the guidelines. This is a multicenter, prospective, observational study on inhaled NO administered through an integrated delivery and monitoring device and indicated for PH according to the market authorizations. The characteristics of NO therapy and ventilation modes were observed. Concomitant pulmonary vasodilator treatments, safety data, and outcome were also collected. Quantitative data are expressed as median (25th, 75th percentile). Over 1 year, 236 patients were included from 14 equipped and trained centers: 117 adults and 81 children with PH associated with cardiac surgery and 38 neonates with persistent PH of the newborn. Inhaled NO was initiated before intensive care unit (ICU) admission in 57%, 12.7%, and 38.9% with an initial dose of 10 (10, 15) ppm, 20 (18, 20) ppm, and 17 (11, 20) ppm, and a median duration of administration of 3.9 (1.9, 6.1) days, 3.8 (1.8, 6.8) days, and 3.1 (1.0, 5.7) days, respectively, for the adult population, pediatric cardiac group, and newborns. The treatment was performed using administration synchronized to the mechanical ventilation. The dose was gradually decreased before withdrawal in 86% of the cases according to the usual procedure of each center. Adverse events included rebound effect for 3.4% (95% confidence interval [CI], 0.9%-8.5%) of adults, 1.2% (95% CI, 0.0%-6.7%) of children, and 2.6% (95% CI, 0.1%-13.8%) of neonates and methemoglobinemia exceeded 2.5% for 5 of 62 monitored patients. Other pulmonary vasodilators were associated with NO in 23% of adults, 95% of children, and 23.7% of neonates. ICU stay was respectively 10 (6, 22) days, 7.5 (5.5, 15) days, and 9 (8, 15) days and ICU mortality was 22.2%, 6.2%, and 7.9% for adults, children, and neonates, respectively. This study confirms the safety of NO therapy in the 3 populations with a low rate of rebound effect. Gradual withdrawal of NO combined with pulmonary vasodilators are current practices in this population. The use of last-generation NO devices allowed good compliance with recommendations.


Randomized Crossover Comparison of Personalized MPC and PID Control Algorithms for the Artificial Pancreas.
To evaluate two widely used control algorithms for an artificial pancreas (AP) under nonideal but comparable clinical conditions. After a pilot safety and feasibility study (n = 10), closed-loop control (CLC) was evaluated in a randomized, crossover trial of 20 additional adults with type 1 diabetes. Personalized model predictive control (MPC) and proportional integral derivative (PID) algorithms were compared in supervised 27.5-h CLC sessions. Challenges included overnight control after a 65-g dinner, response to a 50-g breakfast, and response to an unannounced 65-g lunch. Boluses of announced dinner and breakfast meals were given at mealtime. The primary outcome was time in glucose range 70-180 mg/dL. Mean time in range 70-180 mg/dL was greater for MPC than for PID (74.4 vs. 63.7%, P = 0.020). Mean glucose was also lower for MPC than PID during the entire trial duration (138 vs. 160 mg/dL, P = 0.012) and 5 h after the unannounced 65-g meal (181 vs. 220 mg/dL, P = 0.019). There was no significant difference in time with glucose <70 mg/dL throughout the trial period. This first comprehensive study to compare MPC and PID control for the AP indicates that MPC performed particularly well, achieving nearly 75% time in the target range, including the unannounced meal. Although both forms of CLC provided safe and effective glucose management, MPC performed as well or better than PID in all metrics.


Metallothionein promotes regenerative axonal sprouting of dorsal root ganglion neurons after physical axotomy.
Prior studies have reported that metallothionein I/II (MT) promote regenerative axonal sprouting and neurite elongation of a variety of central nervous system neurons after injury. In this study, we evaluated whether MT is capable of modulating regenerative axon outgrowth of neurons from the peripheral nervous system. The effect of MT was firstly investigated in dorsal root ganglion (DRG) explants, where axons were scratch-injured in the presence or absence of exogenous MT. The application of MT led to a significant increase in regenerative sprouting of neurons 16 h after injury. We show that the pro-regenerative effect of MT involves an interaction with the low-density lipoprotein receptor megalin, which could be blocked using the competitive antagonist RAP. Pre-treatment with the mitogen-activated protein kinase (MAPK) inhibitor PD98059 also completely abrogated the effect of exogenous MT in promoting axonal outgrowth. Interestingly, we only observed megalin expression in neuronal soma and not axons in the DRG explants. To investigate this matter, an in vitro injury model was established using Campenot chambers, which allowed the application of MT selectively into either the axonal or cell body compartments after scratch injury was performed to axons. At 16 h after injury, regenerating axons were significantly longer only when exogenous MT was applied solely to the soma compartment, in accordance with the localized expression of megalin in neuronal cell bodies. This study provides a clear indication that MT promotes axonal regeneration of DRG neurons, via a megalin- and MAPK-dependent mechanism.


Predicting treatment of pulmonary hypertension at discharge in infants with congenital diaphragmatic hernia.
To predict pulmonary hypertension (PH) therapy at discharge in a large multicenter cohort of infants with congenital diaphragmatic hernia (CDH). Six-year linked records from Children's Hospitals Neonatal Database and Pediatric Health Information System were used; patients whose diaphragmatic hernia was repaired before admission or referral, who were previously home before admission or referral, and non-survivors were excluded. The primary outcome was the use of PH medications at discharge and the secondary outcome was an inter-center variation of therapies during inpatient utilization. Clinical factors were used to develop a multivariable equation randomly applied to 80% cohort; validated in the remaining 20% infants. A total of 831 infants with CDH from 23 centers were analyzed. Overall, 11.6% of survivors were discharged on PH medication. Center, duration of mechanical ventilation, and duration of inhaled nitric oxide were associated with the use of PH medication at discharge. This model performed well in the validation cohort area under the receiver operating characteristic curve of 0.9, goodness-of-fit χ2, p = 0.17. Clinical variables can predict the need for long-term PH medication after NICU hospitalization in surviving infants with CDH. This information may be useful to educate families and guide the development of clinical guidelines.


Changes in substance P and 5-HT binding in the spinal cord dorsal horn and lamina 10 after dorsolateral funiculus lesions.
The present study was undertaken to determine whether changes in receptor binding of substance P (SP) and 5-hydroxytryptamine (5-HT) occur in lumbar spinal cord laminae 2, 3, 4 and 10 following interruption of descending SP and 5-HT input. These transmitters and spinal cord regions have been implicated in nociceptive and visceral functions. Quantitative receptor binding autoradiography was used to assess the binding of 2 nM [3H]SP and 2 nM [3H]5-HT to lumbar spinal cord sections taken from normal rats and rats with unilateral thoracic dorsolateral funiculus (DLF) lesions. Postoperative survival times ranged from 1 to 28 days. Substance P binding was above normal in laminae 2 and 3 ipsilateral to the lesion and in contralateral lamina 2 at 1 day postoperatively (DPO), and declined thereafter, reaching below normal levels by 28 DPO. Substance P binding in lamina 10 was significantly above normal at 7 and 14 DPO, but not at 1 or 28 DPO. Binding of 5-HT was above normal at 7 DPO in lamina 2 ipsilateral to the lesion, lamina 3 contralaterally, and lamina 10 bilaterally. These increases were not sustained, however, and at 28 DPO 5-HT binding was significantly below normal in laminae 2-4 bilaterally. The bilateral effects seen in the present study are consistent with the bilaterality of descending thoracic DLF projections demonstrated by the Fink-Heimer method.(ABSTRACT TRUNCATED AT 250 WORDS)


Novel method for mechanical characterization of polymeric nanofibers.
A novel method to perform nanoscale mechanical characterization of highly deformable nanofibers has been developed. A microelectromechanical system (MEMS) test platform with an on-chip leaf-spring load cell that was tuned with the aid of a focused ion beam was built for fiber gripping and force measurement and it was actuated with an external piezoelectric transducer. Submicron scale tensile tests were performed in ambient conditions under an optical microscope. Engineering stresses and strains were obtained directly from images of the MEMS platform, by extracting the relative rigid body displacements of the device components by digital image correlation. The accuracy in determining displacements by this optical method was shown to be better than 50 nm. In the application of this method, the mechanical behavior of electrospun polyacrylonitrite nanofibers with diameters ranging from 300 to 600 nm was investigated. The stress-strain curves demonstrated an apparent elastic-perfectly plastic behavior with elastic modulus of 7.6+/-1.5 GPa and large irreversible strains that exceeded 220%. The large fiber stretch ratios were the result of a cascade of periodic necks that formed during cold drawing of the nanofibers.


Short-pulsed laser transport in two-dimensional scattering media by natural element method.
The natural element method (NEM) is extended to solve transient radiative transfer (TRT) in two-dimensional semitransparent media subjected to a collimated short laser irradiation. The least-squares (LS) weighted residuals approach is employed to spatially discretize the transient radiative heat transfer equation. First, for the case of the refractive index matched boundary, LSNEM solutions to TRT are validated by comparison with results reported in the literature. Effects of the incident angle on time-resolved signals of transmittance and reflectance are investigated. Afterward, the accuracy of this algorithm for the case of the refractive index mismatched boundary is studied. Finally, the LSNEM is extended to study the TRT in a two-dimensional semitransparent medium with refractive index discontinuity irradiated by the short pulse laser. The effects of scattering albedo, optical thickness, scattering phase function, and refractive index on transmittance and reflectance signals are investigated. Several interesting trends on the time-resolved signals are observed and analyzed.


Pharmacogenomics: application to the management of cardiovascular disease.
The past decade has seen substantial advances in cardiovascular pharmacogenomics. Genetic determinants of response to clopidogrel and warfarin have been defined, resulting in changes to the product labels for these drugs that suggest the use of genetic information as a guide for therapy. Genetic tests are available, as are guidelines for incorporation of genetic information into patient-care decisions. These guidelines and the literature supporting them are reviewed herein. Significant advances have also been made in the pharmacogenomics of statin-induced myopathy and the response to β-blockers in heart failure, although the clinical applications of these findings are less clear. Other areas hold promise, including the pharmacogenomics of antihypertensive drugs, aspirin, and drug-induced long-QT syndrome (diLQTS). The potential value of pharmacogenomics in the discovery and development of new drugs is also described. In summary, pharmacogenomics has current applications in the management of cardiovascular disease, with clinically relevant data continuing to mount.


Surveillance for diseases, pathogens, and toxicants of muskrat (Ondatra zibethicus) in Pennsylvania and surrounding regions.
Using diagnostic data and contemporary sampling efforts, we conducted surveillance for a diversity of pathogens, toxicants, and diseases of muskrats (Ondatra zibethicus). Between 1977 and 2019, 26 diagnostic cases were examined from Kansas and throughout the Southeast and Mid-Atlantic, USA. We identified multiple causes of mortality in muskrats, but trauma (8/26), Tyzzer's disease (5/6), and cysticercosis (5/26) were the most common. We also conducted necropsies, during November 2018-January 2019 Pennsylvania muskrat trapping season, on 380 trapper-harvested muskrat carcasses after the pelt was removed. Tissue samples and exudate were tested for presence of or exposure to a suite of pathogens and contaminants. Gastrointestinal tracts were examined for helminths. Intestinal helminths were present in 39.2% of necropsied muskrats, with Hymenolepis spp. (62%) and echinostome spp. (44%) being the most common Molecular testing identified a low prevalence of infection with Clostridium piliforme in the feces and Sarcocystis spp. in the heart. We detected a low seroprevalence to Toxoplasma gondii (1/380). No muskrats were positive for Francisella tularensis or Babesia spp. Cysticercosis was detected in 20% (5/26) of diagnostic cases and 15% (57/380) of our trapper-harvested muskrats. Toxic concentrations of arsenic, cadmium, lead, or mercury were not detected in tested liver samples. Copper, molybdenum, and zinc concentrations were detected at acceptable levels comparative to previous studies. Parasite intensity and abundance were typical of historic reports; however, younger muskrats had higher intensity of infection than older muskrats which is contradictory to what has been previously reported. A diversity of pathogens and contaminants have been reported from muskrats, but the associated disease impacts are poorly understood. Our data are consistent with historic reports and highlight the wide range of parasites, pathogens and contaminants harbored by muskrats in Pennsylvania. The data collected are a critical component in assessing overall muskrat health and serve as a basis for understanding the impacts of disease on recent muskrat population declines.


Developing vaccines for an aging population.
The demographics of the world's population are changing, with many adults now surviving into their 80s. With this change comes the need to protect the aging and other underserved populations not only against infectious diseases but also against cancer and other chronic conditions. New technologies derived from recent advances in the fields of immunology, structural biology, synthetic biology, and genomics have brought a revolution in the vaccine field. Among them, vaccine adjuvants have the potential to harness the immune system to provide protection against new types of diseases, improve protection in young children, and expand this protection to adults and the elderly. However, in order to do so we need also to overcome the nontechnical challenges that could limit the implementation of innovative vaccines, including controversies regarding the safety of adjuvants, increasing regulatory complexity, the inadequate methods used to assess the value of novel vaccines, and the resulting industry alienation from future investment. This Perspective summarizes the outcome of a recent multidisciplinary symposium entitled "Enhancing Vaccine Immunity and Value," held in Siena, Italy, in July 2014, that addressed two related questions: how to improve vaccine efficacy by using breakthrough technologies and how to capture the full potential of novel vaccines.


Rapid motion compensation for prostate biopsy using GPU.
Image-guided procedures have become routine in medicine. Due to the nature of three-dimensional (3-D) structure of the target organs, two-dimensional (2-D) image acquisition is gradually being replaced by 3-D imaging. Specifically in the diagnosis of prostate cancer, biopsy can be performed using 3-D transrectal ultrasound (TRUS) image guidance. Because prostatic cancers are multifocal, it is crucial to accurately guide biopsy needles towards planned targets. Further the gland tends to move due to external physical disturbances, discomfort introduced by the procedure or intrinsic peristalsis. As a result the exact position of the gland must be rapidly updated so as to correspond with the originally acquired 3-D TRUS volume prior to biopsy planning. A graphics processing unit (GPU) is used in this study to compute rapid updates performing 3-D motion compensation via registration of the live 2-D image and the acquired 3-D TRUS volume. The parallel computational framework on the GPU is exploited resulting in mean compute times of 0.46 seconds for updating the position of a live 2-D buffer image containing 91,000 pixels. A 2x sub-sampling resulted in a further improvement to 0.19 seconds. With the increase in GPU multiprocessors and sub-sampling, we observe that real time motion compensation can be achieved.


[Molecular phylogenetic analysis of the genus Abies (Pinaceae) based on the nucleotide sequence of chloroplast DNA].
A phylogenetic study of firs (Abies Mill.) was conducted using nucleotide sequences of several chloroplast DNA regions with a total length of 5580 bp. The analysis included 37 taxa, which represented the main evolutionary lineages of the genus, and Keteleeria daviana. According to phylogenetic reconstruction the Abies species were subdivided into six main groups, generally corresponding to their geographic distribution. The phylogenetic tree had three basal clades. All of these clades contained American species, and only one of them contained Eurasian species. The divergence time calibrations, based on paleobotanical data and the chloroplast DNA mutation rate estimates in Pinaceae, produced similar results..The age of diversification among the clades of the present-day Abies was estimated as the end of the Oligocene-beginning of Miocene. The age of the separation of Mediterranean firs from the Asian-North American branch corresponds to the Miocene. The age of diversification within the young groups of Mediterranean, Asian, and boreal American firs (A. lasiocarpa, A. balsamea, A. fraseri) was estimated as the Pliocene-Pleistocene. Based on the phylogenetic reconstruction obtained, the most plausible biogeographic scenarios were suggested. It is noted that the existing systematic classification of the genus Abies strongly contradicts with phylogenetic reconstruction and requires revision.


Concentration of metabolizable energy and digestibility of energy, phosphorus, and amino acids in lemna protein concentrate fed to growing pigs.
Lemna protein concentrate (LPC; 68.0% CP) is produced by extracting protein from de-oiled and dehydrated biomaterials from plants of the Lemnaceae family and may be used as a protein source for animals. There are, however, no published data on the nutritional value of LPC fed to pigs. Three experiments were, therefore, conducted to determine the concentration of ME, the standardized total tract digestibility (STTD) of P, and the standardized ileal digestibility (SID) of AA in LPC and to compare these values to values for fish meal and soybean meal (SBM). Experiment 1 was conducted to determine the ME of LPC, fish meal, SBM, and corn. Thirty-two barrows (initial BW: 16.8 ± 2.8 kg) were placed in metabolism cages and allotted to a randomized complete block design with 4 diets and 8 replicate pigs per diet. A corn-based diet and 3 diets that contained corn and LPC, fish meal, or SBM were formulated. Feces and urine were collected for 5 d after a 5-d adaptation period, and all samples were analyzed for GE. Results indicated that the concentration of ME was not different among corn, fish meal, and SBM (3,855, 3,904, and 4,184 kcal/kg DM, respectively), but there was a tendency (P = 0.08) for a reduced ME in LPC (3,804 kcal/kg DM) compared with SBM. In Exp. 2, 24 barrows (initial BW: 12.5 ± 2.5 kg) were allotted to a randomized complete block design with 3 diets and 8 replicate pigs per diet and used to determine the STTD of P in LPC, fish meal, and SBM. Three diets that each contained 1 of the 3 test ingredients as the sole source of P were formulated. Pigs were placed in metabolism cages, and feces were collected for 5 d after a 5-d adaptation period. The STTD of P in LPC (72.8%) was not different from the STTD of P in fish meal (65.6%), but tended (P = 0.07) to be greater than in SBM (62.8%). The SID of AA in LPC, SBM, and fish meal was determined in Exp. 3. Eight barrows (initial BW: 21.4 ± 4.0 kg) were equipped with a T-cannula in the distal ileum and randomly allotted to a replicated 4 × 4 Latin square design. A N-free diet and 3 cornstarch-based diets in which SBM, SBM and LPC or SBM and fish meal were the only sources of AA were formulated. The SID of most indispensable AA was greater (P < 0.05) in fish meal than in LPC, but the overall SID of AA was not different between fish meal and LPC. In conclusion, the ME and the STTD of P are not different between LPC and fish meal, but there is a tendency for greater ME in SBM than in LPC, whereas the STTD of P tends to be greater in LPC than in SBM. The SID of the most indispensable AA is greater in fish meal than in LPC.


Stability under vacuum of silicon trap detectors and their use as transfer instruments in cryogenic radiometry.
The stability of the responsivity of trap detectors under vacuum has been studied by means of a special chamber designed for the test of photodetectors at low pressure. The first experiments at a wavelength of 647 nm show that the responsivity variations are smaller than the uncertainties of the measurements, approximately 3 parts in 10(5), when the detector operates successively in air, under vacuum, and then again in air. Calculations based on experiments with single windowless photodiodes indicate that the change in trap responsivity that is due to vacuum effects should be smaller than 1 part in 10(5), at least in the visible part of the wavelength range. This stability makes trap detectors suitable for cryogenic radiometry when one uses transfer detectors under vacuum.


Ultrastructural observations on (pseudo-) exfoliation of the lens capsule: a re-examination of the involvement of the lens epithelium.
One lens each from 2 separate patients suffering from pseudoexfoliation and one lens from a normal eye were examined ultrastructurally. The normal lens capsule was internally lamellar in places and externally of a somewhat reduced electron density but otherwise of a homogeneous appearance and free of inclusions. Observations on the abnormal lenses revealed an electron dense and mainly granular but sometimes fibrillar material along the surface of the peripheral one-third of the capsule. Material of similar ultrastructural appearance was also found deeper in the capsule and in the immediately underlying epithelium. Since the capsule close to the pole of the lens was completely free of these abnormal inclusions and the underlying epithelium also lacked this material, it is concluded that the lens epithelium is a source of the surface debris in pseudoexfoliation. These findings therefore support previous authors who proposed a lenticular involvement in this disease. The present study does, however, not rule out the possibility of a uveal contribution of abnormal material but disputes its exclusive involvement in this disease, as has previously been postulated. Build-up of exfoliated material close to the capsular surface caused an apparent peeling of the lens capsule. It is therefore concluded that the anomalous lenses suffered from a true exfoliative process that may be more correctly termed 'exfoliation of the lens capsule.'


PRN psychotropic medication and acute mental health nursing: reviewing the evidence.
Administration of p.r.n. (pro re nata) medication is a typical practice in acute inpatient mental health units. Although guided by the prescription, the administration of p.r.n. medication is a relatively autonomous component of the nurse's role, and the decision to administer is generally one for the nurse. During a number of facilitated planning days at the authors' facility, nurses indicated that the practice associated with administration of psychotropic p.r.n. medications in an acute inpatient mental health unit required clearer articulation. Against this background, the authors conducted a review of the literature, with two objectives: to identify and then communicate to the nurses the best evidence to support nursing practice. The authors found considerable variation in nursing practices related to administration of p.r.n. medication. In an area of practice that is undertaken with such regularity and with considerable potential impact on consumers, these findings point to the need for further research to establish best practices.


Optimising the computerised adaptive test to reliably reduce the burden of administering the CLEFT-Q: A Monte Carlo simulation study.
Computerised adaptive testing (CAT) has the potential to transform plastic surgery outcome measurement by making patient-reported outcome measures (PROMs) shorter, individualised and more accurate than pen-and-paper questionnaires. This paper reports the results of two optimisation studies for the CLEFT-Q CAT, a CAT intended for use in the field of cleft lip and/or palate. Specifically, we aimed to identify the optimal score estimation and item selection methods for using this CAT in clinical practice. These represent two major components of any CAT algorithm. Monte Carlo simulations were performed using simulated data in the R statistical computing environment and incorporated a range of score estimation and item selection techniques. The performance and accuracy of the CAT was assessed by mean items administered, correlation between CAT scores and paired linear assessment scores, and the root mean squared deviation (RMSD) of these score pairs. The accuracy of the CLEFT-Q CAT was not significantly affected by the choice of score estimation or item selection method. Sub-scales which originally contain more items were amenable to greater item reduction with CAT. This study shows that score estimation and item selection methods that need minimal processing power can be used in the CLEFT-Q CAT without compromising accuracy. This means that the CLEFT-Q CAT could be administered quickly and efficiently with basic hardware demands. We recommend the use of less computationally intensive techniques in future CLEFT-Q CAT studies.


Occupational physical activity and the metabolic syndrome among working women: a Go Red North Dakota study.
To examine the association of metabolic syndrome (MetSyn) with occupational physical activity (OCPA) and leisure-time physical activity (LTPA) among working women. The prevalence of MetSyn was calculated for 642 working women. Self-report questionnaire was used to determine levels of OCPA and LTPA and other lifestyle factors. Biometric data were directly collected on all women. No direct relationship for OCPA and the MetSyn was determined. Sufficient LTPA however, was significantly associated with lower prevalence of MetSyn. No dose response relationship was determined with PA and MetSyn. The odds of having MetSyn was significantly higher for sedentary workers with insufficient LTPA compared with those achieving sufficient LTPA. The odds for MetSyn were similar among women employed in moderately active or heavy work yet completing insufficient LTPA compared with women doing sufficient LTPA. For women with sedentary occupations, a sufficient amount of LTPA is essential to reduce the risk of having the MetSyn. Women in moderate to heavy working occupations may be acquiring adequate amounts of PA to avoid having the MetSyn.


Fully automated software solution for protein quantitation by global metabolic labeling with stable isotopes.
Metabolic stable isotope labeling is increasingly employed for accurate protein (and metabolite) quantitation using mass spectrometry (MS). It provides sample-specific isotopologues that can be used to facilitate comparative analysis of two or more samples. Stable Isotope Labeling by Amino acids in Cell culture (SILAC) has been used for almost a decade in proteomic research and analytical software solutions have been established that provide an easy and integrated workflow for elucidating sample abundance ratios for most MS data formats. While SILAC is a discrete labeling method using specific amino acids, global metabolic stable isotope labeling using isotopes such as (15)N labels the entire element content of the sample, i.e. for (15)N the entire peptide backbone in addition to all nitrogen-containing side chains. Although global metabolic labeling can deliver advantages with regard to isotope incorporation and costs, the requirements for data analysis are more demanding because, for instance for polypeptides, the mass difference introduced by the label depends on the amino acid composition. Consequently, there has been less progress on the automation of the data processing and mining steps for this type of protein quantitation. Here, we present a new integrated software solution for the quantitative analysis of protein expression in differential samples and show the benefits of high-resolution MS data in quantitative proteomic analyses.