Personalized prescription of ACEI/ARBs for hypertensive COVID-19 patients.
The COVID-19 pandemic has prompted an international effort to develop and repurpose medications and procedures to effectively combat the disease. Several groups have focused on the potential treatment utility of angiotensin-converting-enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) for hypertensive COVID-19 patients, with inconclusive evidence thus far. We couple electronic medical record (EMR) and registry data of 3,643 patients from Spain, Italy, Germany, Ecuador, and the US with a machine learning framework to personalize the prescription of ACEIs and ARBs to hypertensive COVID-19 patients. Our approach leverages clinical and demographic information to identify hospitalized individuals whose probability of mortality or morbidity can decrease by prescribing this class of drugs. In particular, the algorithm proposes increasing ACEI/ARBs prescriptions for patients with cardiovascular disease and decreasing prescriptions for those with low oxygen saturation at admission. We show that personalized recommendations can improve patient outcomes by 1.0% compared to the standard of care when applied to external populations. We develop an interactive interface for our algorithm, providing physicians with an actionable tool to easily assess treatment alternatives and inform clinical decisions. This work offers the first personalized recommendation system to accurately evaluate the efficacy and risks of prescribing ACEIs and ARBs to hypertensive COVID-19 patients.


Evidence-based Utilization of Noninvasive Ventilation and Patient Outcomes.
Strong evidence supports use of noninvasive ventilation (NIV) for patients with respiratory distress from chronic obstructive pulmonary disease and heart failure (strong evidence conditions [SECs]). Despite unclear benefits of NIV for other causes of acute respiratory failure, utilization for conditions with weaker evidence is increasing, despite evidence demonstrating higher mortality for patients who suffer NIV failure (progression from NIV to invasive mechanical ventilation [IMV])) compared with being treated initially with IMV. To determine the association of hospital variation in evidence-based utilization of NIV with patient outcomes. Using the California State Inpatient Database 2011, we identified adult patients who received NIV. Patients were considered to have an SEC for NIV if they had an acute exacerbation of chronic obstructive pulmonary disease or heart failure. We used multivariable hierarchical logistic regression to determine the association between hospital rates of NIV use for SECs and patient risk of NIV failure (need for IMV after NIV). Among 22,706 hospitalizations with NIV as the initial ventilatory strategy, 6,820 (30.0%) had SECs. Patients with SECs had lower risk of NIV failure than patients with weak evidence conditions (8.1 vs. 18.2%, P < 0.0001). Regardless of underlying diagnosis, patients admitted to hospitals with greater use of NIV for SECs had lower risk of NIV failure (Quartile 4 vs. Quartile 1 adjusted odds ratio = 0.62; 95% CI = 0.49-0.80). Even patients without an SEC benefited from admission to hospitals that used NIV more often for patients with SECs (Quartile 4 vs. Quartile 1 adjusted odds ratio for NIV failure = 0.68; 95% CI = 0.52-0.88). Most patients who received NIV did not have conditions with strong supporting evidence for its use with wide institutional variation in patient selection for NIV. Surprisingly, we found that all patients, even those without an SEC, benefited from admission to hospitals with greater evidence-based utilization of NIV, suggesting a "hospital effect" that is synergistic with patient selection.


Time-Resolved Quantification of Nanoparticle Uptake, Distribution, and Impact in Precision-Cut Liver Slices.
Much effort within the nanosafety field is currently focused on the use of advanced in vitro models to reduce the gap between in vitro and in vivo studies. Within this context, precision-cut tissue slices are a unique ex vivo model to investigate nanoparticle impact using live tissue from laboratory animals and even humans. However, several aspects of the basic mechanisms of nanoparticle interactions with tissue have not yet been elucidated. To this end, liver slices are exposed to carboxylated and amino-modified polystyrene known to have a different impact on cells. As observed in standard cell cultures, amino-modified polystyrene nanoparticles induce apoptosis, and their impact is affected by the corona forming on their surface in biological fluids. Subsequently, a detailed time-resolved study of nanoparticle uptake and distribution in the tissue is performed, combining fluorescence imaging and flow cytometry on cells recovered after tissue digestion. As observed in vivo, the Kupffer cells accumulate high nanoparticle amounts and, interestingly, they move within the tissue towards the slice borders. Similar observations are reproduced in liver slices from human tissue. Thus, tissue slices can be used to reproduce ex vivo important features of nanoparticle outcomes in the liver and study nanoparticle impact on real tissue.


Quantitative subcellular secondary ion mass spectrometry (SIMS) imaging of boron-10 and boron-11 isotopes in the same cell delivered by two combined BNCT drugs: in vitro studies on human glioblastoma T98G cells.
Ion microscopy was used for subcellular quantitative imaging of the isotopes 10B and 11B in the same cell to evaluate boron delivery using a mixture of two neutron capture therapy drugs, p-boronophenylalanine-fructose (BPA-F) and sodium borocaptate (BSH). The application of 10B-labeled BPA-F and 11B-labeled BSH allowed independent imaging of both 10B and 11B in the same cell using a CAMECA IMS-3f ion microscope. Mixed-drug treatments were compared to single-drug exposures given under identical conditions. 10BPA-F delivered 10B heterogeneously to T98G human glioblastoma cells, with a significantly reduced concentration in an organelle-rich perinuclear region. The intracellular distribution of 11B from 11BSH contrasted with that of the 10B from 10BPA-F, with 11B distributed nearly homogeneously throughout cells. The subcellular distributions of 10B and 11B were sustained in mixed-drug treatments and resembled their localizations after the single-drug treatments. In both single- and mixed-drug treatments, cellular levels of 10B from 10BPA-F nearly doubled between 1 h and 6 h, with a 3:1 intracellular to nutrient medium partitioning, while cellular levels of 11BSH remained essentially unchanged. The net effect of the combined treatment with 10BPA-F and 11BSH was an additive delivery of boron to cells. This study introduces a novel approach for checking potential synergistic, antagonistic or simple additive delivery of two mixed boronated compounds in cellular/subcellular compartments.


Hypertriglyceridemia and Recurrent Pancreatitis following Splenectomy.
Hyperlipoproteinemia represents a constellation of clinical syndromes that frequently includes hypertriglyceridemia. Because of the degree of elevation in the triglyceride levels frequently seen in these syndromes, they are associated with complications not generally observed among those patients with essential hypertriglyceridemia, including as in this case report, recurrent pancreatitis. Here, we present a case of a patient with hyperlipoproteinemia who developed acute worsening of his hypertriglyceridemia and onset of acute panceatitis that became recurrent following elective splenectomy for suspected lymphoma. In particular, we discuss the dietary management of hypertriglyceridemia which significantly reduced the number of episodes of acute pancreatitis in this patient.


Factors associated with medical students' career choices regarding internal medicine.
Shortfalls in the US physician workforce are anticipated as the population ages and medical students' interest in careers in internal medicine (IM) has declined (particularly general IM, the primary specialty serving older adults). The factors influencing current students' career choices regarding IM are unclear. To describe medical students' career decision making regarding IM and to identify modifiable factors related to this decision making. Web-based cross-sectional survey of 1177 fourth-year medical students (82% response rate) at 11 US medical schools in spring 2007. Demographics, debt, educational experiences, and number who chose or considered IM careers were measured. Factor analysis was performed to assess influences on career chosen. Logistic regression analysis was conducted to assess independent association of variables with IM career choice. Of 1177 respondents, 274 (23.2%) planned careers in IM, including 24 (2.0%) in general IM. Only 228 (19.4%) responded that their core IM clerkship made a career in general IM seem more attractive, whereas 574 (48.8%) responded that it made a career in subspecialty IM more attractive. Three factors influenced career choice regarding IM: educational experiences in IM, the nature of patient care in IM, and lifestyle. Students were more likely to pursue careers in IM if they were male (odds ratio [OR] 1.75; 95% confidence interval [CI], 1.20-2.56), were attending a private school (OR, 1.88; 95% CI, 1.26-2.83), were favorably impressed with their educational experience in IM (OR, 4.57; 95% CI, 3.01-6.93), reported favorable feelings about caring for IM patients (OR, 8.72; 95% CI, 6.03-12.62), or reported a favorable impression of internists' lifestyle (OR, 2.00; 95% CI, 1.39-2.87). Medical students valued the teaching during IM clerkships but expressed serious reservations about IM as a career. Students who reported more favorable impressions of the patients cared for by internists, the IM practice environment, and internists' lifestyle were more likely to pursue a career in IM.


[Health risk from active and passive smoking].
This study reviews and updates the health risks of cigarette smoking, based on the studies conducted in European countries, stressing cigarette smoking at the workplace. A review is made of the risks for both sexes, the impact on life expectancy, the advantages of quitting smoking, the social pattern of cigarette smoking in Western societies and the social differences in the diseases caused thereby. A description is also provided of the immediate and long-range effects of passive smoking, the consequences of passive smoking at the workplace and the methods for measuring Environmental Tobacco Smoke.


A generalized equation for the calculation of receptor noise limited colour distances in n-chromatic visual systems.
Researchers must assess similarities and differences in colour from an animal's eye view when investigating hypotheses in ecology, evolution and behaviour. Nervous systems generate colour perceptions by comparing the responses of different spectral classes of photoreceptor through colour opponent mechanisms, and the performance of these mechanisms is limited by photoreceptor noise. Accordingly, the receptor noise limited (RNL) colour distance model of Vorobyev and Osorio (Vorobyev & Osorio 1998 Proc. R. Soc. Lond. B265, 351-358 (doi:10.1098/rspb.1998.0302)) generates predictions about the discriminability of colours that agree with behavioural data, and consequently it has found wide application in studies of animal colour vision. Vorobyev and Osorio (1998) provide equations to calculate RNL colour distances for animals with di-, tri- and tetrachromatic vision, which is adequate for many species. However, researchers may sometimes wish to compute RNL colour distances for potentially more complex colour visual systems. Thus, we derive a simple, single formula for the computation of RNL distance between two measurements of colour, equivalent to the published di-, tri- and tetrachromatic equations of Vorobyev and Osorio (1998), and valid for colour visual systems with any number of types of noisy photoreceptors. This formula will allow the easy application of this important colour visual model across the fields of ecology, evolution and behaviour.


Valve cuspidity: a risk factor for aortic valve repair?
The aim of this study was to analyze short- and mid-term results after aortic valve (AV) repair with particular regard to the impact of valve cuspidity (bicuspid versus tricuspid aortic valve). One hundred patients with aortic regurgitation (AR) undergoing aortic valve repair between November 2007 and October 2012 were included in the study. Sixty patients had bicuspid AV (BAV group; 11 females) and 40 patients had tricuspid AV (TAV group; 13 females). AR > grade 2 was present in 47 (78%) patients in the BAV and in 35 (88%) patients in the TAV group. Follow-up was complete in 100% and median was 25 months. Isolated aortic valve repair was performed in 27 (45%) of BAV patients and in six (15%) of TAV patients. Replacement of the ascending aorta and/or aortic root was performed in 33 (55%) of BAV patients and in 34 (86%) of TAV patients. There was no death within 30 days postoperatively, while two patients died (TAV group) during the follow-up period. There was no statistical difference between BAV and TAV groups with regard to the survival (100 ± 0% vs. 95 ± 4%, p = 0.102), the three-year freedom from AV-related reoperation (90 ± 5% vs. 89 ± 6%, p = 0.456), and the three-year freedom from AR grade > 2 (86 ± 6% vs. 82 ± 7%, p = 0.866), respectively. This study demonstrates no difference in mid-term results after regurgitant bicuspid and tricuspid aortic valve repair, suggesting that bicuspid valve may not be a risk factor for aortic valve repair.


Sucking-pads and primitive sucking reflex.
Sucking pads are hyperkeratotic thickenings of the inner aspect of the vermillion border of the lips of neonates. They develop around the 25th week of gestation and are the result of the primitive sucking reflex which is brain-stem mediated. The presence of sucking pads at birth represents an effective sucking reflex and as such it is recommended as a screening tool that indicates an intact motor neuron function in neonates.


Partial K-Complex Recovery Following Short-Term Abstinence in Individuals with Alcohol Use Disorder.
The K-complex (KC) is a brain potential characteristic of nonrapid eye movement (NREM) sleep resulting from the synchronous activity of a large population of neurons and hypothesized to reflect brain integrity. KC amplitude is lower in individuals with alcohol use disorder (AUD) compared with age-matched controls, but its recovery with short-term abstinence has not been studied. Therefore, we investigated whether the KC shows significant recovery over the first 4 months of abstinence in individuals with AUD. A total of 16 recently abstinent AUD individuals (46.6 ± 9.3 years) and 13 gender and age-matched healthy controls (41.6 ± 8.3 years) were studied on 3 occasions: the Initial session was within 1 month of the AUD individuals' last drink, then 1 and 3 months later. Overnight electroencephalogram was recorded while participants were presented with tones during stage 2 NREM sleep to elicit KCs. At the Initial session, AUD participants showed significantly lower KC amplitude and incidence compared with controls. In the AUD individuals, KC amplitude increased significantly from the Initial to the 1-month session. KC incidence showed a marginally significant increase. Neither KC amplitude nor incidence changed from the 1-month to the 3-month session. No changes in KC amplitude or incidence across sessions were observed in the control group. Our results demonstrate partial KC recovery during the first 2 months of abstinence. This recovery is consistent with the time course of structural brain recovery in abstinent AUD individuals demonstrated by recent neuroimaging results.


Environmental factors in a population-based inception cohort of inflammatory bowel disease patients in Europe--an ECCO-EpiCom study.
The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe possibly due to changes in environmental factors towards a more "westernised" standard of living. The aim of this study was to investigate differences in exposure to environmental factors prior to diagnosis in Eastern and Western European IBD patients. The EpiCom cohort is a population-based, prospective inception cohort of 1560 unselected IBD patients from 31 European countries covering a background population of 10.1 million. At the time of diagnosis patients were asked to complete an 87-item questionnaire concerning environmental factors. A total of 1182 patients (76%) answered the questionnaire, 444 (38%) had Crohn's disease (CD), 627 (53%) ulcerative colitis (UC), and 111 (9%) IBD unclassified. No geographic differences regarding smoking status, caffeine intake, use of oral contraceptives, or number of first-degree relatives with IBD were found. Sugar intake was higher in CD and UC patients from Eastern Europe than in Western Europe while fibre intake was lower (p<0.01). Daily consumption of fast food as well as appendectomy before the age of 20 was more frequent in Eastern European than in Western European UC patients (p<0.01). Eastern European CD and UC patients had received more vaccinations and experienced fewer childhood infections than Western European patients (p<0.01). In this European population-based inception cohort of unselected IBD patients, Eastern and Western European patients differed in environmental factors prior to diagnosis. Eastern European patients exhibited higher occurrences of suspected risk factors for IBD included in the Western lifestyle.


Family history of breast and ovarian cancer and triple negative subtype in hispanic/latina women.
Familial breast and ovarian cancer prevalence was assessed among 1150 women of Mexican descent enrolled in a case-only, binational breast cancer study. Logistic regression was conducted to compare odds of triple negative breast cancer (TNBC) to non-TNBC according to family history of breast and breast or ovarian cancer among 914 of these women. Prevalence of breast cancer family history in a first- and first- or second-degree relative was 13.1% and 24.1%, respectively; that for breast or ovarian cancer in a first-degree relative was 14.9%. After adjustment for age and country of residence, women with a first-degree relative with breast cancer were more likely to be diagnosed with TNBC than non-TNBC (OR=1.98; 95% CI, 1.26-3.11). The odds of TNBC compared to non-TNBC were 1.93 (95% CI, 1.26-2.97) for women with a first-degree relative with breast or ovarian cancer. There were non-significant stronger associations between family history and TNBC among women diagnosed at age <50 compared to ≥50 years for breast cancer in a first-degree relative (P-interaction = 0.14) and a first- or second-degree relative (P-interaction = 0.07). Findings suggest that familial breast cancers are associated with triple negative subtype, possibly related to BRCA mutations in Hispanic/Latina women, which are strongly associated with TNBC. Family history is an important tool to identify Hispanic/Latina women who may be at increased risk of TNBC, and could benefit from prevention and early detection strategies.


Genetic diversity of human enterovirus 68 strains isolated in Kenya using the hypervariable 3'-end of VP1 gene.
Reports of increasing worldwide circulation of human enterovirus-68 (EV68) are well documented. Despite health concerns posed by resurgence of these viruses, little is known about EV68 strains circulating in Kenya. In this study, we characterized 13 EV68 strains isolated in Kenya between 2008 and 2011 based on the Hypervariable 3'-end of the VP1 gene. Viral RNA was extracted from the isolates and partial VP1 gene amplified by RT-PCR, followed by nucleotide sequencing. Alignment of deduced amino acid sequences revealed substitutions in Kenyan EV68 isolates absent in the prototype reference strain (Fermon). The majority of these changes were present in the BC and DE-loop regions, which are associated with viral antigenicity and virulence. The Kenyan strains exhibited high sequence homology with respect to those from other countries. Natural selection analysis based on the VP1 region showed that the Kenyan EV68 isolates were under purifying selection. Phylogenetic analysis revealed that majority (84.6%) of the Kenyan strains belonged to clade A, while a minority belonged to clades B and C. Overall, our results illustrate that although EV68 strains isolated in Kenya were genetically and antigenically divergent from the prototype strain (Fermon), they were closely related to those circulating in other countries, suggesting worldwide transmissibility. Further, the presence of shared mutations by Kenyan EV68 strains and those isolated in other countries, indicates evolution in the VP1 region may be contributing to increased worldwide detection of the viruses. This is the first study to document circulation of EV68 in Kenya.


Sexual function after transvaginal cholecystectomy: a systematic review.
Despite several benefits, patients are concerned that transvaginal cholecystectomy has a negative impact on sexual health. The objective of this systematic review was to assess the impact of transvaginal cholecystectomy on postoperative dyspareunia and sexual function. A literature search was performed in the PubMed and EMBASE databases. Papers reporting on postoperative dyspareunia, vaginal pain or discomfort, and sexual function were included. Seventeen papers reported on dyspareunia and vaginal pain or discomfort. Two papers reported a rate of de novo dyspareunia of 3.8% and 12.5%, respectively. One study reported a nonsignificant reduction in painful sexual intercourse and the remaining 14 reported no incidents of dyspareunia. Eight papers reported on sexual function. One paper using a nonvalidated questionnaire found impaired sexual function. The papers that used validated questionnaires found no impairment of sexual function. The risk of sexual dysfunction and dyspareunia after transvaginal cholecystectomy seems minimal. Well-designed studies using validated questionnaires are necessary to fully assess these types of complications.


Some characteristics and functional properties of rapeseed protein prepared by ultrasonication, ultrafiltration and isoelectric precipitation.
The presence of complex protein constituents and difficulties in extracting protein from rapeseed meal limit the application of rapeseed protein in food processing. However, double-low rapeseed (low erucic acid, low glucosinolate) protein is a type of complete protein that is of potential use in the food industry. In this study the characteristics and functional properties of rapeseed protein prepared by ultrasonic-assisted extraction, ultrafiltration and isoelectric precipitation were analysed and compared with those of soybean protein. The extraction efficiency with the ultrasonic-assisted method was significantly higher than that obtained with the traditional method. Ultrafiltration and isoelectric precipitation yielded three different proteins: ultrafiltered protein RPs and precipitated proteins RP5.8 and RP3.6. Chromatographic separation of RPs resulted in four fractions: RPsI, RPsII, RPsIII and RPsIV. The distribution of the isoelectric point of rapeseed protein was investigated by two-dimensional electrophoresis. The amino acid composition of RPs renders it suitable for human consumption. The hydrophobic/hydrophilic amino acid ratio of rapeseed protein was higher than that of soybean protein. The functional properties (oil adsorption ability, emulsifying capacity, foaming capacity and foam stability) of RPs, RP5.8 and RP3.6 were found to be better than those of soybean protein. Ultrasonication and ultrafiltration were significantly better than the traditional method of rapeseed protein extraction. The ultrafiltered rapeseed protein RPs had superior functional properties. The results of this study provide useful indicators for rapeseed protein as a potential replacement for other proteins.


Automatic multi-structure pediatric knee bone segmentation using optimal multi-level Otsu thresholding to tackle intensity homogeneity in bone structures.
Recent studies in medical image segmentation involve new automatic approaches where active learning models are useful with less training samples. Presence of homogenous and heterogenous intensities for a single anatomical structure in pediatric musculoskeletal MR images affects the accuracy in terms of segmentation and classification of labels. This study addresses the homogeneity in intensity issues and introduces a new pre-training pipeline framework of Multi-level Otsu thresholding image as separate channel for 3D UNet model training. The proposed framework achieved higher performance of up to 85% when compared with the Baseline 3D UNet model and the Histogram threshold with 3D UNet. All algorithms are run through MONAI core framework.Clinical Relevance- This study will be of major interest to practicing pediatric clinicians and surgeons for its ability to provide accurate morphological assessment of underlying musculoskeletal structure. For researchers, it provides a new approach in dealing with heterogeneity in intensity problem which is common in pediatric MR imaging.


What challenges must be overcome before ultrasound elasticity imaging is ready for the clinic?
Ultrasound elasticity imaging has been a research interest for the past 20 years with the goal of generating novel images of soft tissues based on their material properties (i.e., stiffness and viscosity). The motivation for such an imaging modality lies in the fact that many soft tissues can share similar ultrasonic echogenicities, but may have very different mechanical properties that can be used to clearly visualize normal anatomy and delineate diseased tissues and masses. Recently, elasticity imaging techniques have moved from the laboratory to the clinical setting, where clinicians are beginning to characterize tissue stiffness as a diagnostic metric and commercial implementations of ultrasonic elasticity imaging are beginning to appear on the market. This article provides a foundation for elasticity imaging, an overview of current research and commercial realizations of elasticity imaging technology and a perspective on the current successes, limitations and potential for improvement of these imaging technologies.


Bundling Process of Citrulline Polypeptides upon UCST-Type Phase Separation.
Ureido-modified poly(l-citrulline) (l-ornithine-co-l-citrulline denoted by PlOC) shows UCST-type phase separation behavior even under physiologically relevant conditions, which forms an α-helix structure above its phase separation temperature (Tp) but transforms into a solid-like aggregation composed of regular hexagonal packed cylinders below the Tp. This morphological transformation is characteristic of the phase separation behavior, but the mechanism behind it has remained incompletely understood. Here, we studied the phase separation behavior using small-angle X-ray scattering (SAXS) measurements. To analyze the SAXS data, we employed the modified unified model proposed previously, which decomposes the scattering profile into each structural element, such as the α-helices and their aggregation formed via hydrogen-bonding interactions between the ureido groups. The aggregation level is dependent on the temperature (T) and grouped into three classes: (1) mass-fractal aggregation composed of the α-helix (T > Tp), (2) spherical aggregation composed of the hexagonal packed cylinder (T < Tp), and (3) micro-order agglomeration formed by mutual fusion of the spherical aggregation, which appears as a solid-like aggregation. The SAXS analysis suggested that the transformation from the dispersed state as the α-helix to the agglomeration containing hierarchical structures occurs in a stepwise manner when the temperature falls below the Tp, which might also be transition behavior similar to the process of protein folding through folding intermediates.


[Alteration in attention and cancer pain treatment].
Cognitive impairment can negatively impact daily routine. This fact encouraged the elaboration of this study, which analyzed the impact of pain treatment with opioids on attention. Patients were divided into groups that were given (n=14) and were not given opioids (n=12). Three interviews were conducted to assess attention using the Trail Making Test and the Digit Span Test. The groups were homogeneous regarding socio-demographic variables, pain and depression; they were not homogeneous regarding the Karnofsky scale and the use of adjuvant analgesics. The patients in treatment without opioids had better performance in the Digit Span Test-reverse order, in the second assessment (p = 0.29); no differences were observed on the Trail Making Test. The observed impairments were limited, but while new studies do not confirm the findings, patients, professionals and caregivers must be alert about the possible deleterious effects of opioids on the cognitive function.


Vimentin in Bacterial Infections.
Despite well-studied bacterial strategies to target actin to subvert the host cell cytoskeleton, thus promoting bacterial survival, replication, and dissemination, relatively little is known about the bacterial interaction with other components of the host cell cytoskeleton, including intermediate filaments (IFs). IFs have not only roles in maintaining the structural integrity of the cell, but they are also involved in many cellular processes including cell adhesion, immune signaling, and autophagy, processes that are important in the context of bacterial infections. Here, we summarize the knowledge about the role of IFs in bacterial infections, focusing on the type III IF protein vimentin. Recent studies have revealed the involvement of vimentin in host cell defenses, acting as ligand for several pattern recognition receptors of the innate immune system. Two main aspects of bacteria-vimentin interactions are presented in this review: the role of vimentin in pathogen-binding on the cell surface and subsequent bacterial invasion and the interaction of cytosolic vimentin and intracellular pathogens with regards to innate immune signaling. Mechanistic insight is presented involving distinct bacterial virulence factors that target vimentin to subvert its function in order to change the host cell fate in the course of a bacterial infection.


Four States, Four Projects, One Mission: Collectively Enhancing Mental and Behavioral Health Capacity Throughout the Gulf Coast.
The 2010 Deepwater Horizon oil spill triggered numerous concerns regarding the health and well-being of citizens within the already vulnerable Gulf Coast region. Four Mental and Behavioral Health Capacity Projects (MBHCPs) united to form the Quad-State MBHCP component of the Gulf Region Health Outreach Program (GRHOP). Their shared mission was to increase mental and behavioral health (MBH) capacity within coastal counties of Louisiana, Mississippi, Alabama, and the Florida Panhandle. To describe strategies used to collectively enhance the impact of the 4 state-specific MBHCPs and to share lessons learned from a multistate collaborative flexibly designed to meet a shared mission. Archival materials were assessed. They included attendance sheets/notes from regularly scheduled group meetings, GRHOP quarterly and annual reports, and state-specific MBHCP logic models. Nationally available data on MBH services provided in project-relevant primary care sites were also examined. Three strategies were found to be effective facilitators of collective success: (i) reciprocal participation in the backbone organization (GRHOP); (ii) creation and comparison of state-specific MBHCP logic models and activities; and (iii) cross-fertilization among the MBHCP state-specific logic models, a unified Quad-State, and the GRHOP-wide logic model to generate additional synergistic endeavors and measureable outcomes. Examples of region-wide MBHCP success, such as uptake in integrated health services in health care clinics across the jurisdiction of investment, are presented. Isolated approaches to complex issues are, at times, ineffective. The Collective Impact (CI) model, with an emphasis on coordination among existing organizations, stakeholders, and the public, can serve as a guidepost to facilitate sustainable change even when used in a modified form. Strategies discussed herein for maximizing the 5 prescribed CI conditions provide an important roadmap for how to interface among multidisciplinary projects seeking to address the same, large-scale public health problem.


Yield and mineral content of ten enset (Ensete ventricosum) varieties.
A study was conducted to evaluate the macro and trace mineral contents often enset varieties collected from Sidama zone of southern Ethiopia. Samples of leaf lamina, leaf midrib, pseudostem and corm were taken from ten enset varieties at the age of 5 to 6 years during the main rainy season. The dry weight of each variety and fraction were also determined. Mineral contents in fractions of different enset varieties were analysed and compared with nutrient requirements of ruminants. The contribution of different enset fractions to the total dry weight was variable (P<0.05), the highest being from pseudostem and the lowest from leaf lamina. There were varietal differences (P<0.05) in macro and trace mineral content in different fractions except phosphorus (P) content of leaf lamina. Most enset fractions were rich sources of major minerals such as P, potassium (K), calcium (Ca) (except corm) and magnesium (Mg). Sodium (Na) content was very low. Most fractions were rich in iron (Fe) and manganese (Mn), but deficient in copper (Cu), except leaf lamina. Zinc (Zn) content was high in corm, but low in other fractions. This account of the macro and trace mineral content of different enset varieties and fractions could help in strategic supplementation intended to alleviate mineral deficiencies.


Moderate glucose control is associated with increased mortality compared with tight glucose control in critically ill patients without diabetes.
Optimal glucose management in the ICU remains unclear. In 2009, many clinicians at Intermountain Healthcare selected a moderate glucose control (90-140 mg/dL) instead of tight glucose control (80-110 mg/dL). We hypothesized that moderate glucose control would affect patients with and without preexisting diabetes differently. We performed a retrospective cohort analysis of all patients treated with eProtocol-insulin from November 2006 to March 2011, stratifying for diabetes. We performed multivariate logistic regression for 30-day mortality with covariates of age, modified APACHE (Acute Physiology and Chronic Health Evaluation) II score, Charlson Comorbidity score, and target glucose. We studied 3,529 patients in 12 different ICUs in eight different hospitals. Patients with diabetes had higher mean glucose (132 mg/dL vs 124 mg/dL) and greater glycemic variability (SD = 41 mg/dL vs 29 mg/dL) than did patients without diabetes (P < .01 for both comparisons). Tight glucose control was associated with increased frequency of moderate and severe hypoglycemia (30.3% and 3.6%) compared with moderate glucose control (14.3% and 2.0%, P < .01 for both). Multivariate analysis demonstrated that the moderate glucose target was independently associated with increased risk of mortality in patients without diabetes (OR, 1.36; 95% CI, 1.01-1.84; P = .05) but decreased risk of mortality in patients with diabetes (OR, 0.65; 95% CI, 0.45-0.93; P = .01). Moderate glucose control (90-140 mg/dL) may confer greater mortality in critically ill patients without diabetes compared with tight glucose control (80-110 mg/dL). A single glucose target does not appear optimal for all critically ill patients. These data have important implications for the design of future interventional trials as well as for the glycemic management of critically ill patients.


The Impact of Two Combined Oral Contraceptives Containing Ethinyl Estradiol and Drospirenone on Whole Blood Clot Viscoelasticity and the Biophysical and Biochemical Characteristics of Erythrocytes.
Venous thrombosis is associated with combined oral contraceptive (COC) use. We investigated the impact of two ethinyl estradiol (EE) and drospirenone (DRSP) containing COCs (3 mg DRSP/20 µg EE and 3 µg DRSP/30 µg EE) on the viscoelasticity of whole blood clots along with the biophysical and biochemical characteristics of erythrocytes. Thromboelastography (TEG) analysis showed a tendency toward a hypercoagulable state in the COCs groups that was more pronounced with higher EE concentrations. Light microscopy and scanning electron microscopy (SEM) showed rouleaux formation of erythrocytes and alterations to the erythrocyte shape for both COC groups, which was attributed to membrane damage. SEM analysis showed spontaneous activation of fibrin and platelets in the COC groups, along with interactions between erythrocytes and platelets and/or fibrin. Confocal microscopy confirmed compromised membrane integrity in the COC groups compared to controls. Global thrombosis test analysis showed increased platelet activation and low thrombolysis in both COC groups when compared to controls. In conclusion, DRSP/EE formulations impact erythrocytes' biophysical and biochemical properties to cause a shift in hemostasis to a prothrombotic state. Although these effects are mostly subclinical the long-term effects and risks involved with the use of these hormones should be considered carefully for each individual.


Magnesium and muscle performance in older persons: the InCHIANTI study.
The role of magnesium in maintaining muscle integrity and function in older adults is largely unknown. We aimed to investigate the relation between serum magnesium concentrations and muscle performance in older subjects. Data are from the baseline examination conducted between September 1998 and March 2000 of the InCHIANTI (aging in the Chianti area) study, a prospective epidemiologic survey of risk factors for late-life disability. From among 1453 randomly selected community residents completing a home interview, 1138 men (46%) and women (aged 66.7 +/- 15.2 y; x +/- SD) with complete data on muscle performance and serum magnesium who were not severely cognitively compromised and had no evidence of kidney disease or hypercalcemia were included in the analysis. Muscle performance was evaluated by grip strength, lower-leg muscle power, knee extension torque, and ankle extension isometric strength and was normalized for age and body mass index (BMI) within each sex. After adjustment for age, sex, BMI, laboratory variables, presence of chronic diseases, muscle area, muscle density, and physical activity level, serum magnesium concentrations were significantly associated with indexes of muscle performance, including grip strength (beta = 2.0 +/- 0.5, P = 0.0002), lower-leg muscle power (beta = 8.8 +/- 2.7, P = 0.001), knee extension torque (beta = 31.2 +/- 7.9, P < 0.0001), and ankle extension strength (beta = 3.8 +/- 0.5, P < 0.0001). The serum magnesium concentration is an independent correlate of muscle performance in older persons. Whether magnesium supplementation improves muscle function remains to be shown.


Cyclosporin A for immunosuppression: observations in rat heart, pancreas, and islet allograft models and in human renal and pancreas transplantation.
Cyclosporin A (CsA) is a unique immunosuppressive cyclic polypeptide that is currently being used, either alone or in combination with low-dose prednisone, to treat recipients of renal or pancreas allografts in clinical trials. CsA is very effective in preventing rejection of heart and renal allografts in rodents, but in nontoxic doses does not consistently prevent rejection of pancreas and islet allografts. Therefore, we tested low-dose CsA in various combinations with low-dose prednisone, azathioprine, or total lymphoid irradiation in rat heart, pancreas, and islet allograft models. Several combinations are synergistic and when administered continuously can indefinitely prevent rejection of heart allografts, but only delay rejection of pancreatic allografts, transplanted across a major histocompatibility barrier, CsA by itself prolonged the survival of islet allografts transplanted across a minor, but not a major, histocompatibility barrier. CsA and azathioprine had a synergistic effect in the minor histocompatibility barrier islet transplant model, but, in the nontoxic combinations tested, could not prevent rejection indefinitely. A randomized prospective trial comparing standard immunosuppressive therapy (ALG, prednisone, and azathioprine), with CsA and low-dose prednisone for clinical renal allotransplantation is ongoing at the University of Minnesota. Current actuarial 1-yr graft survival is 93% for CsA-treated patients (N = 48) and 81% for conventionally treated patients (N = 52). Patient survival is 98% for CsA and 100% for conventionally treated patients. A pilot trial of CsA in the clinical pancreas transplant program at the University of Minnesota is also underway. Since 1978, 46 pancreas transplants have been performed in 43 patients. Of 30 technically successful pancreatic allografts, 5 of 12 recipients treated with conventional immunosuppression and 6 of 18 recipients treated with CsA currently have functioning grafts and are insulin independent between 1 and 44 months after transplantation. The results of metabolic studies are similar in conventional and CsA-treated patients with functioning pancreas grafts. Since pancreas grafts may fail for reasons other than rejection, further observations are needed to ascertain the role of CsA in clinical pancreas transplantation.


Augmented Reality, Serious Games and Picture Exchange Communication System for People with ASD: Systematic Literature Review and Future Directions.
For people with Autism Spectrum Disorder (ASD), using technological tools, such as augmented reality (AR) and serious games remain a new and unexplored option. To attract people with ASD who have communicative, social, emotional and attention deficit disorders to behavioral treatments, an attractive environment is needed that ensures continuity during treatment. The aim of the current work is to efficiently examine systematic reviews and relevant primary studies on ASD solutions from 2015 to 2020, particularly those using the traditional Picture Exchange Communication System (PECS), the application of augmented reality and those that propose serious games, thereby providing an overview of existing evidence and to identify strategies for future research. Five databases were searched for keywords that may be included within the broad Autism Spectrum Disorder 'ASD' umbrella term, alongside 'augmented reality', 'serious games' and 'PECS'. We screened 1799 titles and abstracts, read, and retained 12 reviews and 43 studies. The studies scrutinized in our systematic review were examined to answer four primary and four sub-research questions, which we formulated to better understand general trends in the use of approaches for attracting people with ASD to behavioral therapies. Additionally, our systematic review also presents ongoing issues in this area of research and suggests promising future research directions. Our review is useful to researchers in this field as it facilitates the comparison of existing studies with work currently being conducted, based on the availability of a wide range of studies in three different areas (AR, SG and PECS).


Detection and characterization of infectious DNA intermediates of a primary foamy virus.
DNA from human T-lymphoid (Molt-4) and hamster kidney (BHK-21) cells infected with the T-lymphotropic simian foamy virus LK-3 was shown to be infectious, when assayed by transfection of BHK-21 cells. The proviral genome was further characterized by blot hybridization to a specific cDNA probe, which had been prepared by reverse transcription in vitro using viral RNA and RNA-dependent DNA polymerase present in cytoplasmic extracts of infected BHK-21 cells. This probe hybridized to a DNA species of 14 kbp in extracts from LK-3-infected diploid human fibroblasts, Molt-4 and BHK-21 cells, whereas no hybridization occurred with DNA from the respective uninfected controls. No integrated proviral DNA could be demonstrated, and the 14 kbp DNA was shown not to represent circular DNA. The patterns of restriction endonuclease and S1 nuclease fragments indicated a unique configuration of linear double-stranded DNA containing a single-stranded section separating two subunits one of which may be sufficient to transmit LK-3 by transfection with DNA.


Targeting prenylation inhibition through the mevalonate pathway.
Protein prenylation is a critical mediator in several diseases including cancer and acquired immunodeficiency syndrome (AIDS). Therapeutic intervention has focused primarily on directly targeting the prenyltransferase enzymes, FTase and GGTase I and II. To date, several drugs have advanced to clinical trials and while promising, they have yet to gain approval in a medical setting due to off-target effects and compensatory mechanisms activated by the body which results in drug resistance. While the development of dual inhibitors has mitigated undesirable side effects, potency remains sub-optimal for clinical development. An alternative approach involves antagonizing the upstream mevalonate pathway enzymes, FPPS and GGPPS, which mediate prenylation as well as cholesterol synthesis. The development of these inhibitors presents novel opportunities for dual inhibition of cancer-driven prenylation as well as cholesterol accumulation. Herein, we highlight progress towards the development of inhibitors against the prenylation machinery.


A simple Bayesian estimate of direct RNAi gene regulation events from differential gene expression profiles.
Microarrays are commonly used to investigate both the therapeutic potential and functional effects of RNA interfering (RNAi) oligonucleotides such as microRNA (miRNA) and small interfering RNA (siRNA). However, the resulting datasets are often challenging to interpret as they include extensive information relating to both indirect transcription effects and off-target interference events. In an attempt to refine the utility of microarray expression data when evaluating the direct transcriptional affects of an RNAi agent we have developed SBSE (Simple Bayesian Seed Estimate). The key assumption implemented in SBSE is that both direct regulation of transcription by miRNA, and siRNA off-target interference, can be estimated using the differential distribution of an RNAi sequence (seed) motif in a ranked 3' untranslated region (3' UTR) sequence repository. SBSE uses common microarray summary statistics (i.e. fold change) and a simple Bayesian analysis to estimate how the RNAi agent dictated the observed differential expression profile. On completion a trace of the estimate and the location of the optimal partitioning of the dataset are plotted within a simple graphical representation of the 3'UTR landscape. The combined estimates define the differential distribution of the query motif within the dataset and by inference are used to quantify the magnitude of the direct RNAi transcription effect. SBSE has been evaluated using five diverse human RNAi microarray focused investigations. In each instance SBSE unambiguously identified the most likely location of the direct RNAi effects for each of the differential gene expression profiles. These analyses indicate that miRNA with conserved seed regions may share minimal biological activity and that SBSE can be used to differentiate siRNAs of similar efficacy but with different off-target signalling potential.


TATA-binding protein and transcription factor IIB induce transcript slipping during early transcription by RNA polymerase II.
To better understand the mechanism of steps in early transcription by RNA polymerase II (pol II), we investigated the molecular determinants of transcript slipping within complexes assembled on promoters containing a pre-melted transcription bubble from -9 to +3. Transcript slippage occurs when an RNA transcript contains a repetitive sequence that allows the transcript to slip back and pair with the template strand of the DNA at a new register before transcription continues. We established the contributions of individual transcription factors, DNA elements, and RNA length to slipping on a heteroduplex template using a highly purified human pol II transcription system. We found that transcripts slip at a very defined point in the transcription reaction, after pol II completes phosphodiester bond synthesis at register +5. This point is set by the position of the polymerase active site on the DNA template, as opposed to the length of the transcript, as well as by a repetitive CUCU sequence that must occur from +2 to +5. Interestingly, slipping at this juncture is induced by TATA-binding protein and transcription factor IIB and requires a TATA box but not a transcription factor IIB recognition sequence. We propose a model in which transcribing complexes, upon completing phosphodiester bond synthesis at register +5, enter one of two branches in which they either complete productive synthesis of the transcript or undergo multiple rounds of transcript slipping.


Analytical aspects of volatile substance abuse (VSA).
Through a case report, the authors illustrate the volatile substance abuse (VSA) toxicological investigation difficulties mainly due to evaporation of the compounds from postmortem samples and to the lack of reference data for interpretation. A 17-year-old man, student in a chemistry institute, was found dead with a plastic bag placed over his head. Several chemical substances were found in his belongings. Autopsy findings included serious pulmonary lesions and hemorrhagic digestive ulcerations. A large screening of drugs and toxic compounds and selective analyses for several classes of drugs of abuse were carried out in the autopsy samples. In particular, a headspace (HS), -gas chromatography/-mass spectrometry (GC/MS) technique was used to screen for volatile substances and metabolites in the biological samples and for residues of volatile substances on the surface of the plastic bag and in the chemicals found on the scene. The main analytical finding was the presence of alkanes (heptane, methyl-2-pentane, methyl-3-hexane, methylcyclohexane) in the gastric content. The literature data, VSA practices, long time-delay between death and autopsy, preservation conditions of the biological samples before analysis, and in-lab experiments on evaporation of volatile substances were considered to interpret this result. The present fatality was attributed to VSA with a gasoline-based stain remover like "eau écarlate," associated with a hypoxic recreation practice using a plastic bag.


Downregulation of N-terminal acetylation triggers ABA-mediated drought responses in Arabidopsis.
N-terminal acetylation (NTA) catalysed by N-terminal acetyltransferases (Nats) is among the most common protein modifications in eukaryotes, but its significance is still enigmatic. Here we characterize the plant NatA complex and reveal evolutionary conservation of NatA biochemical properties in higher eukaryotes and uncover specific and essential functions of NatA for development, biosynthetic pathways and stress responses in plants. We show that NTA decreases significantly after drought stress, and NatA abundance is rapidly downregulated by the phytohormone abscisic acid. Accordingly, transgenic downregulation of NatA induces the drought stress response and results in strikingly drought resistant plants. Thus, we propose that NTA by the NatA complex acts as a cellular surveillance mechanism during stress and that imprinting of the proteome by NatA is an important switch for the control of metabolism, development and cellular stress responses downstream of abscisic acid.


Measured energy content of frequently purchased restaurant meals: multi-country cross sectional study.
To measure the energy content of frequently ordered meals from full service and fast food restaurants in five countries and compare values with US data. Cross sectional survey. 223 meals from 111 randomly selected full service and fast food restaurants serving popular cuisines in Brazil, China, Finland, Ghana, and India were the primary sampling unit; 10 meals from five worksite canteens were also studied in Finland. The observational unit was frequently ordered meals in selected restaurants. Meal energy content, measured by bomb calorimetry. Compared with the US, weighted mean energy of restaurant meals was lower only in China (719 (95% confidence interval 646 to 799) kcal versus 1088 (1002 to 1181) kcal; P<0.001). In analysis of variance models, fast food contained 33% less energy than full service meals (P<0.001). In Finland, worksite canteens provided 25% less energy than full service and fast food restaurants (mean 880 (SD 156) versus 1166 (298); P=0.009). Country, restaurant type, number of meal components, and meal weight predicted meal energy in a factorial analysis of variance (R2=0.62, P<0.001). Ninety four per cent of full service meals and 72% of fast food meals contained at least 600 kcal. Modeling indicated that, except in China, consuming current servings of a full service and a fast food meal daily would supply between 70% and 120% of the daily energy requirements for a sedentary woman, without additional meals, drinks, snacks, appetizers, or desserts. Very high dietary energy content of both full service and fast food restaurant meals is a widespread phenomenon that is probably supporting global obesity and provides a valid intervention target.


Characterization of chicken epidermal dendritic cells.
It has been known for 15 years that the chicken epidermis contains ATPase+ and major histocompatibility complex class II-positive (MHCII+) dendritic cells. These cells were designated as Langerhans cells but neither their detailed phenotype nor their function was further investigated. In the present paper we demonstrate a complete overlapping of ATPase, CD45 and vimentin staining in all dendritic cells of the chicken epidermis. The CD45+ ATPase+ vimentin+ dendritic cells could be divided into three subpopulations: an MHCII+ CD3- KUL01+ and 68.1+ (monocyte-macrophage subpopulation markers) subpopulation, an MHCII- CD3- KUL01- and 68.1- subpopulation and an MHCII- CD3+ KUL01- and 68.1- subpopulation. The first population could be designated as chicken Langerhans cells. The last population represents CD4- CD8- T-cell receptor-alphabeta- and -gammadelta- natural killer cells with cytoplasmic CD3 positivity. The epidermal dendritic cells have a low proliferation rate as assessed by bromodeoxyuridine incorporation. Both in vivo and in vitro experiments showed that dendritic cells could be mobilized from the epidermis. Hapten treatment of epidermis resulted in the decrease of the frequency of epidermal dendritic cells and hapten-loaded dendritic cells appeared in the dermis or in in vitro culture of isolated epidermis. Hapten-positive cells were also found in the so-called dermal lymphoid nodules. We suggest that these dermal nodules are responsible for some regional immunological functions similar to the mammalian lymph nodes.


Rare Earth impurities in yb(6) and zrb(12).
We present data on the depression of the superconducting transition temperatures of YB(6) and ZrB(12) by rare earth impurities. These data show unusual features. Ce in YB(6) is in some ways analogous to Yb in ZrB(12), and this analogy also appears to hold between Ce in CeB(6) and YB in YbB(12).


Synergistic effect of stromelysin-1 (matrix metallo-proteinase-3) promoter 5A/6A polymorphism with smoking on the onset of young acute myocardial infarction.
The objective of this study was to elucidate the association between the polymorphism of stromelysin-1, also called matrix metalloproteinases-3 (MMP-3), and smoking in the pathogenesis of young acute myocardial infarction (MI). Plaque rupture is well established as a critical factor in the pathogenesis of acute MI. MMP-3 can degrade extracellular matrix and are identified extensively in human coronary atheroslcerotic plaques, and may contribute to the weakening of the cap and subsequent rupture. We studied 150 consecutive patients with acute MI onset at age under 45 years (84% men) and 150 sex- and age-matched control subjects. 5A/6A genotype in the stromelysin-1 promoter was determined using polymerase chain reaction and direct sequencing. Results show that the frequency of the 5A allele and the prevalence of 5A/5A + 5A/6A genotypes were both significantly higher in the young MI than the control group (35.0% vs. 20.0%, odds ratio [OR] 2.15, 95% confidence interval [CI] 1.30 to 6.80, p<0.001; 44.7% vs. 27.4%, OR 2.19, 95% CI 1.21 to 3.98, p=0.009). Multiple logistic regression analysis showed that the 5A allele was an independent risk factor (OR 2.36, 95% CI 1.24 to 5.90, p=0.008) as were as smoking (OR 3.92, 95% CI 1.75 to 9.21, p=0.001), diabetes mellitus (OR 3.51, 95% CI 1.41 to 6.32, p=0.0068) and hypertension (OR 1.85, 95% CI 1.35 to 4.33, p=0.0025) for the premature onset of MI. Compared to 6A/6A subjects, among patients who did not smoke, the 5A allele polymorphism was associated with a higher risk of MI at a young age (OR 2.69, 95% CI 1.3 to 8.6), but smoking carriers of the 5A allele had a significantly 10-fold higher risk of MI (OR 9.98, 95% CI 2.3 to 12.5). We can conclude that there was a significant association between the 5A/6A polymorphism in the promoter region of stromelysin-1 gene and young MI in Taiwan. A synergistic effect between smoking and this polymorphism for the premature onset of MI had been shown in this study.


Investigation of composite materials using SLM-based phase retrieval.
We present a robust method to inspect a typical composite material constructed of carbon fiber reinforced plastic (CFRP). It is based on optical surface contouring using the spatial light modulator (SLM)-based phase retrieval technique. The method utilizes multiple intensity observations of the wave field, diffracted by the investigated object, captured at different planes along the optical axis to recover the phase information across the object plane. The SLM-based system allows for the recording of the required consecutive intensity measurements in various propagation states across a common recording plane. This overcomes the mechanical shifting of a camera sensor required within the capturing process. In contrast to existing phase retrieval approaches, the measuring time is considerably reduced, since the switching time of the SLM is less than 50 ms. This enables nondestructive testing under thermal load. Experimental results are presented that demonstrate the approach can be used to assess structural properties of technical components made from CFRP.


Feasibility and integration of an intensive emergency pediatric care curriculum in Armenia.
Emergency pediatric care curriculum (EPCC) was developed to address the need for pediatric rapid assessment and resuscitation skills among out-of-hospital emergency providers in Armenia. This study was designed to evaluate the effectiveness of EPCC in increasing physicians' knowledge when instruction transitioned to local instructors. We hypothesize that (1) EPCC will have a positive impact on post-test knowledge, (2) this effect will be maintained when local trainers teach the course, and (3) curriculum will satisfy participants. This is a quasi-experimental, pre-test/post-test study over a 4-year period from October 2014‑November 2017. Train-the-trainer model was used. Primary outcomes are immediate knowledge acquisition each year and comparison of knowledge acquisition between two cohorts based on North American vs local instructors. Descriptive statistics was used to summarize results. Pre-post change and differences across years were analyzed using repeated measures mixed models. Test scores improved from pretest mean of 51% (95% CI 49.6 to 53.0%) to post-test mean of 78% (95% CI 77.0 to 79.6%, p < 0.001). Average increase from pre- to post-test each year was 27% (95% CI 25.3 to 28.7%). Improvement was sustained when local instructors taught the course (p = 0.74). There was no difference in improvement when experience in critical care, EMS, and other specialties were compared (p = 0.23). Participants reported satisfaction and wanted the course repeated. In 2017, EPCC was integrated within the Emergency Medicine residency program in Armenia. This program was effective at impacting immediate knowledge as well as participant satisfaction and intentions to change practice. This knowledge acquisition and reported satisfaction remained constant even when the instruction was transitioned to the local instructors after 2 years. Through a partnership between the USA and Armenia, we provided OH-EPs in Armenia with an intensive educational experience to attain knowledge and skills necessary to manage acutely ill or injured children in the out-of-hospital setting. EPCC resulted in significant improvement in knowledge and was well received by participants. This is a viable and sustainable model to train providers who have otherwise not had formal education in this field.


Hypertension after renal transplantation.
The incidence of hypertension (mean diastolic pressure above 90 mm Hg) was evaluated in 85 patients with renal transplants whose follow-up ranged from 3 to 84 months. Bilateral nephrectomy had been performed in 80 recipients. The proportion of hypertensive subjects rose during the first three months, subsequently stabilised around 50-60% for up to five years, and then decreased slightly during the next two years. Over the years hypertension fluctuated so that one-third of the initially hypertensive patients became normotensive, and over one-third of the initially normotensive patients became hypertensive. The main single aetiological factor was renal failure. A significant relation between steroid dosage and blood pressure was found in only a quarter of the hypertensive patients, and in another quarter no cause could be found.


Sex and age specific effects of delta-9-tetrahydrocannabinol during the periadolescent period in the rat: The unique susceptibility of the prepubescent animal.
Adolescents who use marijuana are more likely to exhibit anxiety, depression, and other mood disorders, including psychotic-like symptoms. Additionally, the age at onset of use and the stress history of the individual can affect responses to cannabis. To examine the effect of early life experience on adolescent Δ-9-tetrahydrocannabinol (THC) exposure, we exposed adolescent (postnatal day (P) 29-38) male and female rats, either shipped from a supplier or born in our vivarium, to once daily injections of 3mg/kg THC. Our findings suggest that males are more sensitive to the anxiolytic and antidepressant effects of THC, as measured by the elevated plus maze (EPM) and forced swim test (FST), respectively, than females. Exposure to the FST increased plasma corticosterone levels, regardless of drug treatment or origin and females had higher levels than males overall. Shipping increased THC responses in females (acoustic startle habituation) and in males (latency to immobility in FST). No significant effects of THC or shipping on pre-pulse inhibition were observed. Due to differences in timing of puberty in males and females during the P29-38 period of THC treatment, we also dosed female rats between P21-30 (pre-puberty) and male rats between P39-48 (puberty). Pre-pubertal animals showed reductions in anxiety on the EPM, an effect that was not seen in animals treated during puberty. These results suggest that both sexes are more susceptible to changes in emotional behavior when THC exposure occurs just prior to the onset of puberty. Within the animals dosed from P29-38, THC increased cannabinoid receptor 1 (CB1R) mRNA expression and tended to decrease CP55,940 stimulated [35S]GTPγS binding in the central amygdala only of females. Therefore, early stress enhances THC responses in males (in FST) and females (ASR habituation), THC alters CB1R expression and function in females only and prepubescent rats are generally more responsive to THC than pubertal rats. In summary, THC and stress interact with the developing endocannabinoid system in a sex specific manner during the peri-pubertal period.


Structural differences between parent and mutant H-2K glycoproteins from two H-2K gene mutants: b6.c-h-2ba (Hzl) and B6-H-2bd (M505).
The H-2K glycoproteins from two mouse mutants B6.C-H-2ba (Hzl) and B6-H-2bd (M505) were isolated, and by tryptic peptide mapping techniques, were compared with each other and with the H-2K glycoprotein from the parent strain C57BL/6 (H-2b). The elution profile of the acid-soluble tryptic peptides from the H-2Kba glycoprotein showed that at least two to three arginine-labeled peptides and one lysine-labeled peptide were different from the H-2Kb product of the parent. These peptides were distinct from the soluble peptides which constitute the difference which was found between the H-2K products of H-2bd and the H-2b parent strains. The comparative peptide maps thus demonstrate small but significant primary structural differences among the H-2Kba, H-2Kbd, and H-2Kb glycoproteins. The findings are in agreement with the suggestion that alterations in the H-2K products from these two mutants are sufficient to permit their cells to stimulate each other and the parent cells in the mixed lymphocyte reaction (MLR) and to serve as target cells for the cell-mediated lymphocytotoxicity (CML) test. Because there is a significant reactivity in MLR and CML between H-2Kb, H-2Kba and H-2Kbd cells whereas there is no serologic reactivity, our findings are consistent with the notion there is a separation of the site(s) on the H-2 molecule having serologic reactivity and the site(s) involved in the MLR and CML reactivities.


Nonrenal indications for continuous renal replacement therapy: A report from the Prospective Pediatric Continuous Renal Replacement Therapy Registry Group.
Continuous renal replacement therapy is the most often implemented dialysis modality in the pediatric intensive care unit setting for patients with acute kidney injury. However, it also has a role in the management of patients with nonrenal indications such as clearance of drugs and intermediates of disordered cellular metabolism. Using data from the multicenter Prospective Pediatric Continuous Renal Replacement Therapy Registry, we report a cohort of pediatric patients receiving continuous renal replacement therapy for nonrenal indications. Nonrenal indications were obtained from the combination of "other" category for continuous renal replacement therapy initiation and patient diagnosis (both primary and secondary). This cohort was further divided into three subgroups: inborn errors of metabolism, drug toxicity, and tumor lysis syndrome. From 2000 to 2005, a total of 50 continuous renal replacement therapy events with nonrenal indications for therapy were included in the Prospective Pediatric Continuous Renal Replacement Therapy Registry. Indication-specific survival of the subgroups was 62% (inborn errors of metabolism), 82% (tumor lysis syndrome), and 95% (drug toxicity). The median small solute dose delivered among the subgroups ranged from 2125 to 8213 mL/1.73 m/hr, with 54%-59% receiving solely diffusion-based clearance as continuous venovenous hemodialysis. No association was established between survival and dose delivered, modality of continuous renal replacement therapy, or use of intermittent hemodialysis prior to continuous renal replacement therapy. Pediatric patients requiring continuous renal replacement therapy for nonrenal indications are a distinct cohort within the population receiving renal replacement therapy with little published experience of outcomes for this group. Survival within this cohort varies by indication for continuous renal replacement therapy and is not associated with continuous renal replacement therapy modality. Additionally, survival is not associated with small solute doses delivered within a cohort receiving >2000 mL/1.73 m/hr. Our data suggest metabolic control is established rapidly in pediatric patients and that acute detoxification may be provided with continuous renal replacement therapy for both the initial and maintenance phases of treatment using either convection or diffusion at appropriate doses.


PKC-dependent activation of p46/p54 JNKs during ischemic preconditioning in conscious rabbits.
A conscious rabbit model was used to study the effect of ischemic preconditioning (PC) on stress-activated kinases [c-Jun NH(2)-terminal kinases (JNKs) and p38 mitogen-activated protein kinase (MAPK)] in an environment free of surgical trauma and attending external stress. Ischemic PC (6 cycles of 4-min ischemia/4-min reperfusion) induced significant activation of protein kinase C (PKC)-epsilon in the particulate fraction, which was associated with activation of p46 JNK in the nuclear fraction and p54 JNK in the cytosolic fraction; all of these changes were completely abolised by the PKC inhibitor chelerythrine. Selective enhancement of PKC-epsilon activity in adult rabbit cardiac myocytes resulted in enhanced activity of p46/p54 JNKs, providing direct in vitro evidence that PKC-epsilon is coupled to both kinases. Studies in rabbits showed that the activation of p46 JNK occurred during ischemia, whereas that of p54 JNK occurred after reperfusion. A single 4-min period of ischemia induced a robust activation of the p38 MAPK cascade, which, however, was attenuated after 5 min of reperfusion and disappeared after six cycles of 4-min ischemia/reperfusion. Overexpression of PKC-epsilon in cardiac myocytes failed to increase the p38 MAPK activity. These results demonstrate that ischemic PC activates p46 and p54 JNKs via a PKC-epsilon-dependent signaling pathway and that there are important differences between p46 and p54 JNKs with respect to the subcellular compartment (cytosolic vs. nuclear) and the mechanism (ischemia vs. reperfusion) of their activation after ischemic PC.


Pigmented Villonodular Synovitis: Potential Pitfall on Oncologic 18F-FDG PET/CT.
This study evaluated the semiquantitative and qualitative appearance of pigmented villonodular synovitis (PVNS) and giant cell tumor of the tendon sheath (GCTTS) on 18F-FDG PET/CT. An institutional review board-approved retrospective review was performed for patients diagnosed with GCTTS, focal PVNS, or diffuse PVNS who underwent PET/CT from 2003 to 2013. SUVmax and SUVmax/SUVmean of the liver (SUVr) were determined for each lesion on all available PET/CTs. Relevant conventional imaging and patient records were reviewed. Fourteen patients (mean [SD] age, 52.8 [14.0] years; range, 26-74 years) were identified, 6 with 2 or more PET/CT examinations. The mean (SD) SUVmax and SUVr of all lesions were 8.7 (3.4; range, 4.0-14.5) and 3.9 (1.7; range, 2.0-7.1), respectively. There was no difference of the mean (SD) SUVmax (P = 0.10) or SUVr (P = 0.11) between focal PVNS (6.8 [3.0], 3.3 [1.9]), GCTTS (9.1 [3.0], 4.0 [1.2]), or diffuse PVNS (14.5, 7.1) subtypes. Of 29 comparison PET/CTs in 6 patients, 17 were performed after nontargeted chemotherapy and 12 without antecedent therapy. Significant SUVr fluctuations (>25%) occurred in 11 cases; no correlation existed between SUVr change and presence or absence of chemotherapy. Pigmented villonodular synovitis and GCTTS can be intensely hypermetabolic, mimicking musculoskeletal metastases on 18F-FDG PET/CT. They may have significant SUV fluctuations, both during nontargeted chemotherapy and between treatments. The diagnosis of PVNS/GCTTS should be considered for focal intra-articular or juxta-articular FDG-avid lesions, and MRI is useful in further evaluation given the often diagnostic imaging features with this modality.


Tomographic active optical trapping of arbitrarily shaped objects by exploiting 3D refractive index maps.
Optical trapping can manipulate the three-dimensional (3D) motion of spherical particles based on the simple prediction of optical forces and the responding motion of samples. However, controlling the 3D behaviour of non-spherical particles with arbitrary orientations is extremely challenging, due to experimental difficulties and extensive computations. Here, we achieve the real-time optical control of arbitrarily shaped particles by combining the wavefront shaping of a trapping beam and measurements of the 3D refractive index distribution of samples. Engineering the 3D light field distribution of a trapping beam based on the measured 3D refractive index map of samples generates a light mould, which can manipulate colloidal and biological samples with arbitrary orientations and/or shapes. The present method provides stable control of the orientation and assembly of arbitrarily shaped particles without knowing a priori information about the sample geometry. The proposed method can be directly applied in biophotonics and soft matter physics.


Prostate MRI technical parameters standardization: A systematic review on adherence to PI-RADSv2 acquisition protocol.
The Prostate Imaging-Reporting and Data System has been developed to standardize prostate MRI in terms of acquisition, interpretation and reporting. It received a major revision in late 2014 (PI-RADSv2). Recently, doubts have been raised on imaging facilities adherence to its acquisition protocol. With this systematic review, we assessed adherence to PI-RADSv2 minimum technical specifications in literature, to achieve a better understanding of issues limiting their diffusion. Multiple medical literature databases were extensively searched to retrieve original studies published after January 2016 performing prostate MRI. Information pertaining acquisition protocols and patient enrolment were recorded for analysis. Technical parameters were dichotomized in relation to adherence to the corresponding minimal technical requirements. A total of 150 studies were included for analysis. Only 5% reported every technical parameter specified in the PI-RADSv2 document requirements, none of which completely met guideline specifications. Overall, 19% were in line with PI-RADSv2 for all reported MRI acquisition parameters. The adherence was lowest for T2-weighted frequency in-plane resolution (12%), diffusion-weighted imaging field of view (40%), apparent diffusion coefficient map low b-value (27%) and dynamic contrast-enhanced imaging temporal resolution (43%). Considering its role in image interpretation, it must be highlighted that only 59% of studies reporting diffusion-weighted imaging high b-value follow recommendations. Adherence to PI-RADSv2 minimum technical standards is heterogeneous in the scientific community. Our findings endorse the need for greater diffusion of PI-RADSv2 guidelines to achieve protocol standardization and support the notion that some requirements might benefit from streamlining to improve clinical applicability.


Audit of donor centre: guidelines by the World Marrow Donor Association Quality and Regulation Working Group.
According to the Standards of the World Marrow Donor Association (WMDA) 2020 [1] unrelated stem cell donor registries are responsible for compliance of their donor centres with these Standards. To ensure high stem cell product quality and high standards for safety and satisfaction of voluntary unrelated stem cell donors, we present here guidelines for audits of donor centres (DC) that can be used by new and established donor registries. They have been developed for registries relying on independent national or international DCs for the recruitment and management of Unrelated Donors (UD) for verification typing (VT)/extended tying (ET), work up processes and Hemopoietic Progenitor Cell (HPC) donation. The main goal of these guidelines is to support registries in verifying and auditing their affiliated DCs to ensure they are compliant with the WMDA Standards, as well as WMDA recommendations. We define the general requirements and recommendations for collaboration with the DC and guidelines to manage the UD, step by step from recruitment to follow-up. We also provide a checklist, intended to serve as a resource for auditors performing an audit at a DC.


Stroke survivor perceptions of using an exoskeleton during acute gait rehabilitation.
Robotic-assisted gait training (RAGT) devices allow intensive high repetition of the gait cycle in individuals with locomotor disability, with reduced therapist effort. In addition to usual rehabilitation, RAGT post-stroke improves the likelihood of regaining independent walking, with maximum efficacy identified in the acute and subacute phases of stroke. This study explores the usability and acceptance of RAGT among persons with stroke in an acute hospital setting and examines users' perceptions of two different modes of robotic assistance provided during rehabilitation. A mixed-methods approach comprised semi-structed interviews of end-user perspectives of RAGT in an acute hospital setting following stroke and two 10-point Likert scales rating how comfortable and how natural robotic gait felt using different assistance modes. Content analysis of qualitative data was undertaken with results synthesised by common meaning units. Quantitative data were reported using summary statistics, with Spearmann's correlation co-efficient examining the relationship between Likert scale ratings and measures of participants' stroke related disability. Ten individuals (6 men; 4 women; mean age of 64.5. ± 13 years) were recruited in an acute hospital setting following admission with a stroke diagnosis. Content analysis of interview transcripts identified discussion units centring around positive aspects of how helpful the device was, negative aspects related to set-up time, weight of the device and multiple instructions delivered during use. Initially participants identified that the device could look intimidating, and they feared falling in the device but they subsequently identified the correct mindset for using the device is to trust the technology and not be afraid. Mean ratings for device comfort (7.94 ± 1.4) and how natural walking felt (7.05 ± 1.9) were favourable. Interestingly, a strong relationship was identified, whereby the higher the level of disability, the more natural participants rated walking in the device during maximal assistance mode (rho = 0.62; p = 0.138). This study suggests individuals in the early phases of stroke perceive RAGT to be acceptable and helpful in the main, with some associated negative aspects. Walking in the device was rated as comfortable and natural. Those with greater disability rated the assisted walking as more natural.


Antibodies as probes for ligand gating of single sarcoplasmic reticulum Ca2(+)-release channels.
A large (565 kDa) junctional sarcoplasmic reticulum (SR) protein, the ryanodine receptor (RYR), may play both a structural and a functional role in the mechanism of skeletal muscle excitation-contraction coupling. Recently, the primary amino acid sequence of the RYR has been elucidated. In this paper, we introduce an immunological approach to examine the functional (electrophysiological) properties of the RYR when it is incorporated into planar lipid bilayers. The effects of two polyclonal antibodies against the SR junctional face membrane (JFM) and the RYR (anti-JFM and anti-RYR) were tested on the single-channel gating properties of the RYR SR Ca2(+)-release channel. Junctional SR vesicles were fused into planar lipid bilayers in solutions containing caesium salts. Solutions were designed to minimize the background conductances of the SR K+ and Cl- channels. Three actions of the anti-JFM antibody were distinguished on the basis of single-channel gating and conductance. The anti-RYR antibody had a single action, a simultaneous decrease in single-channel open probability (Po) and conductance. Both antibodies appear to alter single-channel gating by disrupting the Ca2(+)-activation mechanism of the channel. Anti-RYR-antibody-induced gating abnormalities were reversed by ATP, although the ATP-re-activated channels had altered gating kinetics. Two antigenic regions, recognizing the anti-RYR antibody, in the C-terminal end of the RYR primary amino acid sequence contain or are closely associated with putative ligand (Ca2+ and ATP)-binding sites identified previously. Our results demonstrate (1) that the antibodies induced abnormal gating (decreased open probability and stabilization of subconducting states) of SR release channels, and (2) that abnormal gating is not associated with physical obstruction or alteration of the conduction pathway. Thus antibodies directed at specific regions of the RYR (e.g. putative ligand-binding sites) can be used as effective probes with which to study the structural and functional properties of the SR Ca2(+)-release channel gating at the single-channel level.


Chemical constituents of the aerial parts of Salvia judaica Boiss. from Jordan.
Investigation of the chemical constituents of Salvia judaica growing wild in Jordan led to the isolation and identification of 15 known compounds. These included: luteolin-3'-methyl ether (1), indole-3-carboxyaldehyde (2), p-hydroxybenzaldehyde (3), tricin (4), apigenin (5), methyl isoferuloyl-7-(3,4-dihydroxyphenyl) lactate (6), methyl rosmarinate (7), rosmarinic acid (8), salvigenin (9), β-sitosterol (10), 3β, 28-dihydroxyurs-12-ene (11), cirsilineol (12), 2,3-dihydroxyurs-12-en-28-oic acid (13), β-sitosteryl glucoside (14), and tormentic acid (15). Compounds 6 and 7 exhibited strong radical scavenging and chelating activities as compared to α-tocopherol and ascorbic acid, compound 7 showed a 2-fold greater antioxidant activity as compared to compound 6. Furthermore, low doses of compounds 6 and 7 were able to inhibit the growth of leukemic (HL-60, Jurkat, K562 and CCRF-SB) and solid tumor cells (MCF-7, MDA-MB-231 and Caco-2). Compound 7 showed a ca. 3-4-fold stronger cytotoxicity against the tested cells as compared to compound 6.


Retro-Claisen benzylation: direct use of benzyl alcohols in Pd-catalyzed couplings with nitriles.
A new strategy has been developed for the benzylation of nitriles directly from benzyl alcohols. In this process benzyl alcohols undergo retro-Claisen activation with cyanoacetic esters to generate an active electrophile and a carbanionic nucleophile. In the presence of Pd(0) these intermediates undergo catalytic coupling to generate a new C-C bond, resulting in the formation of phenyl propionitriles.


Controllable synthesis of CeO2/g-C3N4 composites and their applications in the environment.
This research has developed a photocatalytic reactor that includes circulating water, light, and a temperature control system. CeO2/g-C3N4 composites with high photocatalytic activity and stability were synthesized by a simple and facile hydrothermal method. The obtained photocatalysts were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS). It was found that in the CeO2/g-C3N4 composites, the CeO2 nanoparticles were homogeneously cubic in shape (from 3 to 10 nm) and were evenly dispersed on the surface of the g-C3N4. At constant temperature (30 °C), 5% CeO2/g-C3N4 photocatalyst showed the best photocatalytic activity for degrading organic dye methylene blue (MB) under visible light irradiation. The photocatalytic reaction for degrading MB followed first-order kinetics and 5% CeO2/g-C3N4 exhibited a higher apparent rate of 1.2686 min(-1), 7.8 times higher than that of the pure g-C3N4 (0.1621 min(-1)). In addition, it was found that 5% CeO2/g-C3N4 had a new property that it could be used as a sensor for the determination of trace amounts of Cu(2+). Such unique design and one-step synthesis, with an exposed high-activity surface, are important for both technical applications and theoretical investigations.


The current and future impact of human papillomavirus on treatment of squamous cell carcinoma of the head and neck.
Squamous cell carcinoma of the head and neck (SCCHN) was traditionally associated with smoking and alcohol use; however, human papillomavirus (HPV) infection has recently been implicated as a novel risk factor for oropharyngeal tumors. Furthermore, HPV-associated oropharyngeal carcinoma (OPC) appears to be a distinct entity with different epidemiology, biology, and clinical outcomes. Here, we comprehensively review the existing data regarding HPV status and prognostic or predictive outcomes in both the locoregionally advanced (LA) and recurrent/metastatic (RM) disease setting and discuss ongoing trials that may eventually impact the treatment of patients with HPV-positive (HPV+) SCCHN. A body of retrospective and prospective data established an association between HPV+ OPC and better survival, particularly for LA disease. Current data on RM disease are limited, but they also suggest prognostic significance for HPV. Better outcomes in HPV+ LA disease may allow for less aggressive treatment in the future, and several trials are evaluating deintensified regimens in patients with HPV+, LA OPC; it should be emphasized that deintensification strategies are appropriate only in a clinical research setting and only for selected subgroups of HPV+ patients. In addition, HPV-targeted strategies, such as vaccines, are currently undergoing clinical evaluation. On the other hand, the prognostic impact of HPV in RM disease requires further validation before any modifications in treatment can be made. Likewise, the predictive significance of HPV status in both disease settings remains to be defined. NCT00226239, NCT00301028, NCT00387127, NCT00410826, NCT00503997, NCT00514943, NCT00544414, NCT00768664, NCT00939627, NCT01084083, NCT01302834, NCT01687413, NCT01706939.


Inactivation dates of the human and guinea pig vitamin C genes.
The capacity to biosynthesize ascorbic acid has been lost in a number of species including primates, guinea pigs, teleost fishes, bats, and birds. This inability results from mutations in the GLO gene coding for L-gulono-γ-lactone oxidase, the enzyme responsible for catalyzing the last step in the vitamin C biosynthetic pathway. We analyzed available primate and rodent GLO gene sequences to determine their evolutionary history. We used a method based on sequence comparisons of lineages with and without functional GLO genes to calculate inactivation dates of 61 and 14 MYA for the primate and guinea pig genes, respectively. These estimates are consistent with previous phylogeny-based estimates. An analysis of transposable element distribution in the primate and rodent GLO sequences did not reveal conclusive evidence that illegitimate recombination between repeats has contributed to the loss of exons in the primate and guinea pig genes.


Structural analysis of ribosomal DNA homologues in nucleolus-less mutant of Xenopus laevis.
Sequences homologous to the ribosomal DNA (rDNA) in a Xenopus anucleolate (nucleolus-less) mutant were analyzed by Southern blot analysis. The mutant was found to possess a variety of sequences homologous to non-transcribed spacer (NTS) and/or coding region of rDNA. 65 rDNA-homologous clones were isolated from a genomic DNA library of the mutant. All the clones showed only partial homology to the normal rDNA unit and their restriction maps differed from that of the normal rDNA unit. Based on the hybridization patterns, the rDNA-homologous clones were divided into four groups (I-IV). Structure of group IV, which most strongly hybridized to normal rDNA probe, was analyzed by nucleotide sequencing. The group IV sequence was found to contain a part of the rDNA, including Bam island, enhancer element, promoter region, external transcribed spacer, and a portion of 18S rRNA gene. The blotting analysis suggested that the group IV sequence is specific for a particular strain of Xenopus.


Evaluation of the Effectiveness of Brazilian Community Restaurants for the Dimension of Low-Income People Access to Food.
This study aimed to evaluate the effectiveness of community restaurants (CRs), managed by the Government of the State of Bahia/Brazil, for the dimension of access to food. The study used secondary data obtained from the public opinion survey Profile of users of community restaurants in Salvador. The nutritional information was accessed through the analysis of CRs' menus. Adequate effectiveness of access to food was considered when the CR served meals to 50% to 70% of the users considered the target audience (individuals served by the two CRs located in the city of Salvador/Bahia/Brazil). The participants (n = 1464; 778 as low-income individuals) were adult CR users from Salvador/Brazil. Most of the respondents were male, 40 to 54 years old, not white, had up to 9 years of formal education, without a partner, and living in the municipality of Salvador. The evaluated CRs are effective in serving 53.1% of the target population in their total service capacity. Meal provision only reached an estimated 0.7% of the socially vulnerable community in the district. The average energy value of the meal served by the CR units was 853.05 kcal/meal, with a mean energy density composition classified as average (1.15 kcal/g). The effectiveness of the evaluated community restaurants showed that these instruments were minimally effective in promoting access to food for the low-income population within their total daily service capacity, and the current quantity of these facilities was insufficient. However, these instruments stand out in the fundamental role of promoting the daily distribution of meals to the Brazilian population with the highest social vulnerability levels.


Vasoconstrictor response of arterioles of the hamster cheek pouch to norepinephrine, prostaglandin H2, F2 alpha and carbocyclic thromboxane A2, a possible thromboxane A2 analogue.
Activated platelets produce thromboxane A2, a potent vasoconstrictor, which may play an important role in pathophysiological disturbances of microcirculation. Thromboxane A2 has a very short half life and has neither been isolated nor synthesized. Hence, the recently reported stable analogue, carbocyclic thromboxane A2 (CTA2), may become an interesting tool in pharmacological research. Its vasoconstrictor potency was compared in vivo with norepinephrine, prostaglandin H2 and F2 alpha using the following method: vessels of a hamster cheek pouch preparation were exposed to a superfusion to which the respective compounds were added to give 1 ng/ml to 0.1 mg/ml final concentrations. The decrease of vessel diameters was measured microscopically. Prostaglandin H2 was found to be the most potent vasoconstrictor followed by CTA2 and norepinephrine. Prostaglandin F2 alpha was least effective. The respective maximal vasoconstrictory responses did not differ significantly.


Diaphragm pacing with a quadripolar phrenic nerve electrode: an international study.
We sought to determine the international experience with the quadripolar diaphragm pacer system and to test two hypotheses: the incidence of pacer complications would be (1) increased among pediatric as compared to adult patients; and (2) highest among active pediatric patients with idiopathic congenital central hypoventilation syndrome (CCHS). Data were collected via a questionnaire coupled with the Atrotech Registry data for a total of 64 patients (35 children and 29 adults) from 14 countries. Thoracic implantation of electrodes and bilateral pacer use each occurred in 94% of all subjects. Tetraplegic (vs pediatric CCHS) patients were more typically paced 24 hours/day (P = 0.001). Pacing duration averaged 2.0 +/- 1.0 years among children and 2.2 +/- 1.1 years among adults. Infections occurred among 2.9% of surgical procedures, all in pediatric CCHS patients (vs pediatric tetraplegic patients, P = 0.01). The incidence of mechanical trauma was 3.8%, without significant differences among patient groups. The incidence of presumed electrode and receiver failure were 3.1% and 5.9%, respectively, with internal component failure greater among pediatric CCHS than pediatric tetraplegic patients (P < 0.01). Intermittent or absent function of 0-4 electrode combinations occurred among 19% of all patients, with increased frequency among pediatric CCHS than pediatric tetraplegic patients (P < 0.03). Complication-free successful pacing occurred in 60% of pediatric and 52% of adult patients. In all, 94% of the pediatric and 86% of the adult patients paced successfully after the necessary intervention. Although pacer complications were not increased among pediatric as compared to adult patients, the incidence of complications was highest among the active pediatric patients with CCHS. Longitudinal study of these patients will provide invaluable information for modification and improvement of the quadripolar system.


Perspective of the GEMSTONE Consortium on Current and Future Approaches to Functional Validation for Skeletal Genetic Disease Using Cellular, Molecular and Animal-Modeling Techniques.
The availability of large human datasets for genome-wide association studies (GWAS) and the advancement of sequencing technologies have boosted the identification of genetic variants in complex and rare diseases in the skeletal field. Yet, interpreting results from human association studies remains a challenge. To bridge the gap between genetic association and causality, a systematic functional investigation is necessary. Multiple unknowns exist for putative causal genes, including cellular localization of the molecular function. Intermediate traits ("endophenotypes"), e.g. molecular quantitative trait loci (molQTLs), are needed to identify mechanisms of underlying associations. Furthermore, index variants often reside in non-coding regions of the genome, therefore challenging for interpretation. Knowledge of non-coding variance (e.g. ncRNAs), repetitive sequences, and regulatory interactions between enhancers and their target genes is central for understanding causal genes in skeletal conditions. Animal models with deep skeletal phenotyping and cell culture models have already facilitated fine mapping of some association signals, elucidated gene mechanisms, and revealed disease-relevant biology. However, to accelerate research towards bridging the current gap between association and causality in skeletal diseases, alternative in vivo platforms need to be used and developed in parallel with the current -omics and traditional in vivo resources. Therefore, we argue that as a field we need to establish resource-sharing standards to collectively address complex research questions. These standards will promote data integration from various -omics technologies and functional dissection of human complex traits. In this mission statement, we review the current available resources and as a group propose a consensus to facilitate resource sharing using existing and future resources. Such coordination efforts will maximize the acquisition of knowledge from different approaches and thus reduce redundancy and duplication of resources. These measures will help to understand the pathogenesis of osteoporosis and other skeletal diseases towards defining new and more efficient therapeutic targets.


Mechanics of penta-graphene with vacancy defects under large amplitude tensile and shear loading.
Penta-graphene is a new two-dimensional metastable carbon allotrope composed entirely of carbon pentagons with unique electronic and mechanical properties. In this work we evaluate the mechanical properties of new classes of defective penta-graphene (DPG) subjected to tensile and shear loading by using molecular dynamics simulations. The types of defects considered here are monovacancy at either 4-coordinated C1 site or 3-coordinated C2 site, and double vacancy (DV). We focus in particular on the effects of the different topologies of defects and their concentrations on the elastic constants and the nonlinear mechanics of this allotropic form of carbon. The results indicate that DPG has a plastic behavior similar to pristine penta-graphene, which is caused by the irreversible pentagon-to-polygon structural transformation occurring during tensile and shear loading. The tensile and shear moduli decrease linearly with the concentration of defects. Monotonic reductions of the tensile yield and shear stresses are also present but less pronounced, while the yield strains are unaffected. Penta-graphene with 4-coordinated and DVs feature a change of the Poisson's ratio from negative to positive when the defect concentration rises to about 3% and 6%. Temperature can trigger structural reconstruction for free-standing DPG. The critical transition temperature increases due to the vacancy defects and the defects can delay the structure transition. These findings are expected to provide important guidelines for the practical applications of penta-graphene based micro/nano electromechanical systems.


Impact of peroxisome proliferator-activated receptor-α on diabetic cardiomyopathy.
The prevalence of cardiomyopathy is higher in diabetic patients than those without diabetes. Diabetic cardiomyopathy (DCM) is defined as a clinical condition of abnormal myocardial structure and performance in diabetic patients without other cardiac risk factors, such as coronary artery disease, hypertension, and significant valvular disease. Multiple molecular events contribute to the development of DCM, which include the alterations in energy metabolism (fatty acid, glucose, ketone and branched chain amino acids) and the abnormalities of subcellular components in the heart, such as impaired insulin signaling, increased oxidative stress, calcium mishandling and inflammation. There are no specific drugs in treating DCM despite of decades of basic and clinical investigations. This is, in part, due to the lack of our understanding as to how heart failure initiates and develops, especially in diabetic patients without an underlying ischemic cause. Some of the traditional anti-diabetic or lipid-lowering agents aimed at shifting the balance of cardiac metabolism from utilizing fat to glucose have been shown inadequately targeting multiple aspects of the conditions. Peroxisome proliferator-activated receptor α (PPARα), a transcription factor, plays an important role in mediating DCM-related molecular events. Pharmacological targeting of PPARα activation has been demonstrated to be one of the important strategies for patients with diabetes, metabolic syndrome, and atherosclerotic cardiovascular diseases. The aim of this review is to provide a contemporary view of PPARα in association with the underlying pathophysiological changes in DCM. We discuss the PPARα-related drugs in clinical applications and facts related to the drugs that may be considered as risky (such as fenofibrate, bezafibrate, clofibrate) or safe (pemafibrate, metformin and glucagon-like peptide 1-receptor agonists) or having the potential (sodium-glucose co-transporter 2 inhibitor) in treating DCM.