Multi-country analysis of treatment costs for HIV/AIDS (MATCH): facility-level ART unit cost analysis in Ethiopia, Malawi, Rwanda, South Africa and Zambia.
Today's uncertain HIV funding landscape threatens to slow progress towards treatment goals. Understanding the costs of antiretroviral therapy (ART) will be essential for governments to make informed policy decisions about the pace of scale-up under the 2013 WHO HIV Treatment Guidelines, which increase the number of people eligible for treatment from 17.6 million to 28.6 million. The study presented here is one of the largest of its kind and the first to describe the facility-level cost of ART in a random sample of facilities in Ethiopia, Malawi, Rwanda, South Africa and Zambia. In 2010-2011, comprehensive data on one year of facility-level ART costs and patient outcomes were collected from 161 facilities, selected using stratified random sampling. Overall, facility-level ART costs were significantly lower than expected in four of the five countries, with a simple average of $208 per patient-year (ppy) across Ethiopia, Malawi, Rwanda and Zambia. Costs were higher in South Africa, at $682 ppy. This included medications, laboratory services, direct and indirect personnel, patient support, equipment and administrative services. Facilities demonstrated the ability to retain patients alive and on treatment at these costs, although outcomes for established patients (2-8% annual loss to follow-up or death) were better than outcomes for new patients in their first year of ART (77-95% alive and on treatment). This study illustrated that the facility-level costs of ART are lower than previously understood in these five countries. While limitations must be considered, and costs will vary across countries, this suggests that expanded treatment coverage may be affordable. Further research is needed to understand investment costs of treatment scale-up, non-facility costs and opportunities for more efficient resource allocation.


The usefulness of C-reactive protein and procalcitonin to predict prognosis in septic shock patients: A multicenter prospective registry-based observational study.
The objective of this study was to evaluate the prognostic value of C-reactive protein (CRP), procalcitonin (PCT), and their combination for mortality in patients with septic shock. This multicenter, prospective, observational study was conducted between November 2015 and December 2017. A total of 1,772 septic shock patients were included, and the overall 28-day mortality was 20.7%. Although both CRP and PCT were elevated in the non-survivor group, only CRP had statistical significance (11.9 mg/dL vs. 14.7 mg/dL, p = 0.003, 6.4 ng/mL vs. 8.2 ng/mL, p = 0.508). Multivariate analysis showed that CRP and PCT were not independent prognostic markers. In the subgroup analysis of the CRP and PCT combination matrix using their optimal cut-off values (CRP 14.0 mg/dL, PCT 17.0 ng/dL), both CRP and PCT elevated showed significantly higher mortality (Odds ratio 1.552 [95% Confidence intervals 1.184-2.035]) than both CRP and PCT not elevated (p = 0.001) and only PCT elevated (p = 0.007). However, both CRP and PCT elevated was also not an independent predictor in multivariate analysis. Initial levels of CRP and PCT alone and their combinations in septic shock patients had a limitation to predict 28-day mortality. Future research is needed to determine new biomarkers for early prognostication in patients with septic shock.


Establishment of a conditionally immortalized mouse optic nerve astrocyte line.
Optic nerve astrocytes play a major role in axonal degeneration and regeneration. Astrocyte lines are an important tool to elucidate the responsible cellular mechanisms. In this study, we established a conditionally immortalized mouse optic nerve astrocyte line. Astrocytes were cultured from explants derived from postnatal day 4-5 H-2kb-tsA58 transgenic mouse optic nerves. Cells were cultured in defined astrocyte culture medium under permissive (33 °C) or non-permissive (38.5 °C) temperatures with or without interferon-ɤ (IFN-ɤ). Astrocytes were characterized by immunocytochemistry staining using antibodies against glial fibrillary acidic protein (GFAP) and neural cell adhesion molecule (NCAM). Cell proliferation rates were determined by cell growth curves and percentage of Ki67 positive cells. Karyotyping was performed to validate the mouse origin of established cell line. Conditional immortalization was assessed by western blot-determined expression levels of SV40 large T antigen (TAg), p53, GFAP and NCAM in non-permissive culture conditions. In addition, phagocytic activity of immortalized cells was determined by flow cytometry-based pHrodo fluorescence analysis. After 5 days in culture, cells migrated out from optic nerve explants. Immunocytochemistry staining showed that migrating cells expressed astrocyte makers, GFAP and NCAM. In permissive conditions, astrocytes had increased expression levels of TAg and p53, exhibited a greater cell proliferation rate as well as a higher percentage of Ki67 positive cells (n = 3, p < 0.05) compared to cells cultured in non-permissive conditions. One cell line (ImB1ON) was further maintained through 60 generations. Karyotyping showed that ImB1ON was of mouse origin. Flow cytometry-based pHrodo fluorescence analysis demonstrated phagocytic activity of ImB1ON cells. Quantitative PCR showed mRNA expression of trophic factors. Non-permissive culture conditions decreased expression of TAg and p53 in ImB1ON, and increased the expression of NCAM. A conditionally immortalized mouse optic nerve astrocyte line was established. This cell line provides an important tool to study astrocyte biological processes.


Protons and Ca2+: ionic allies in tumor progression?
Ion channels and G-protein-coupled receptors (GPCRs) play a fundamental role in cancer progression by influencing Ca(2+) influx and signaling pathways in transformed cells. Transformed cells thrive in a hostile environment that is characterized by extracellular acidosis that promotes the pathological phenotype. The pathway(s) by which extracellular protons achieve this remain unclear. Here, a role for proton-sensing ion channels and GPCRs as mediators of the effects of extracellular protons in cancer cells is discussed.


Carbon substrate re-orders relative growth of a bacterium using Mo-, V-, or Fe-nitrogenase for nitrogen fixation.
Biological nitrogen fixation is catalyzed by the molybdenum (Mo), vanadium (V) and iron (Fe)-only nitrogenase metalloenzymes. Studies with purified enzymes have found that the 'alternative' V- and Fe-nitrogenases generally reduce N2 more slowly and produce more byproduct H2 than the Mo-nitrogenase, leading to an assumption that their usage results in slower growth. Here we show that, in the metabolically versatile photoheterotroph Rhodopseudomonas palustris, the type of carbon substrate influences the relative rates of diazotrophic growth based on different nitrogenase isoforms. The V-nitrogenase supports growth as fast as the Mo-nitrogenase on acetate but not on the more oxidized substrate succinate. Our data suggest that this is due to insufficient electron flux to the V-nitrogenase isoform on succinate compared with acetate. Despite slightly faster growth based on the V-nitrogenase on acetate, the wild-type strain uses exclusively the Mo-nitrogenase on both carbon substrates. Notably, the differences in H2 :N2 stoichiometry by alternative nitrogenases (~1.5 for V-nitrogenase, ~4-7 for Fe-nitrogenase) and Mo-nitrogenase (~1) measured here are lower than prior in vitro estimates. These results indicate that the metabolic costs of V-based nitrogen fixation could be less significant for growth than previously assumed, helping explain why alternative nitrogenase genes persist in diverse diazotroph lineages and are broadly distributed in the environment.


Characterization of 23 small supernumerary marker chromosomes detected at pre-natal diagnosis: The value of fluorescence in situ hybridization.
Small supernumerary marker chromosomes (sSMCs) cannot be identified or characterized unambiguously by conventional cytogenetic banding techniques. Until recently, the large variety of marker chromosomes, as well as the limitations in their identification, have presented a diagnostic problem. In order to determine the origin of sSMCs, we used a variety of fluorescence in situ hybridization (FISH) methods, including centromere-specific multicolor FISH, acrocentric specific multicolor FISH, subcentromere-specific multicolor FISH and multicolor FISH with whole chromosome paint probes. Moreover, uniparental disomy testing was in all cases attempted. From a total of 28,000 pre-natal samples from four diagnostic genetics laboratories in Greece, 23 (0.082%) supernumerary marker chromosomes were detected. The mean maternal age was 36.2 years (range 27-43) and the mean gestational age at which amniocentesis was performed was 18.5 weeks (range 16-23). Eighteen markers were de novo and 5 markers were inherited. Molecular cytogenetic methods were applied to determine the chromosomal origin and composition of the sSMC. In total, 17 markers were derived from acrocentric chromosomes (14, 15, 21 and 22) and 6 markers were non-acrocentric, derived from chromosomes 9, 16, 18, 20 and Y. Uniparental disomy was not detected in any of the cases studied. With regard to pregnancy outcome, 13 pregnancies resulted in normal healthy neonates, while 10 pregnancies were terminated due to ultrasound abnormalities. A total of 23 marker chromosomes from 28,000 pre-natal samples (0.082%) were identified. Molecular cytogenetic techniques provided valuable information on the chromosomal origin and composition of all the sSMCs. Especially in cases with normal ultrasound, the FISH results rendered genetic counseling possible in a category of cases previously considered a diagnostic problem. Abnormal outcome was observed in 10 cases (43,5%), 7 of which showed abnormal ultrasound findings. New technologies, such as array-comparative genomic hybridization, should be used in future genotype-phenotype correlation studies, although the high mosaicism rate poses a problem.


Validation of the Get With The Guideline-Heart Failure risk score in Japanese patients and the potential improvement of its discrimination ability by the inclusion of B-type natriuretic peptide level.
Detailed characteristics of patients with acute heart failure (AHF) in Japan have not been elucidated. Furthermore, international application of risk models obtained in the United States has not been validated. We evaluated the Get With The Guidelines-Heart Failure (GWTG-HF) risk score performance in AHF patients enrolled in the West Tokyo Heart Failure registry, a large, ongoing, prospective, multicenter cohort registry. Variables required for the GWTG-HF risk score were race, age, systolic blood pressure, heart rate, blood urea nitrogen level, sodium concentration, and presence of chronic obstructive pulmonary disease. Score discrimination and calibration were evaluated by the c statistic, Hosmer-Lemeshow statistic, and visual plotting. We conducted additional analyses to determine whether other variables improved the performance of the score. The primary outcome was in-hospital mortality. In total, 1,876 patients were admitted for AHF between April 2006 and August 2014. The patients were predominantly men (60.6%), with a mean age of 73.3 ± 13.6 years. Sixty-eight (3.6%) patients died during hospitalization. The GWTG-HF risk score showed acceptable discrimination; the c statistic for in-hospital mortality in this cohort was 0.763 (95% CI, 0.700-0.826). The calibration plot showed good conformance between the predicted and observed in-hospital mortality. Notably, addition of B-type natriuretic peptide level to the conventional GWTG-HF score significantly improved the discrimination (c statistic, 0.818; 95% CI, 0.771-0.865). The GWTG-HF risk score can be applied in Japanese AHF patients with good discrimination and calibration. Furthermore, addition of B-type natriuretic peptide level improves discrimination and could be considered in future risk models.


An effector of the Irish potato famine pathogen antagonizes a host autophagy cargo receptor.
Plants use autophagy to safeguard against infectious diseases. However, how plant pathogens interfere with autophagy-related processes is unknown. Here, we show that PexRD54, an effector from the Irish potato famine pathogen Phytophthora infestans, binds host autophagy protein ATG8CL to stimulate autophagosome formation. PexRD54 depletes the autophagy cargo receptor Joka2 out of ATG8CL complexes and interferes with Joka2's positive effect on pathogen defense. Thus, a plant pathogen effector has evolved to antagonize a host autophagy cargo receptor to counteract host defenses.


Dynamic bulge nucleotides in the KSHV PAN ENE triple helix provide a unique binding platform for small molecule ligands.
Cellular and virus-coded long non-coding (lnc) RNAs support multiple roles related to biological and pathological processes. Several lncRNAs sequester their 3' termini to evade cellular degradation machinery, thereby supporting disease progression. An intramolecular triplex involving the lncRNA 3' terminus, the element for nuclear expression (ENE), stabilizes RNA transcripts and promotes persistent function. Therefore, such ENE triplexes, as presented here in Kaposi's sarcoma-associated herpesvirus (KSHV) polyadenylated nuclear (PAN) lncRNA, represent targets for therapeutic development. Towards identifying novel ligands targeting the PAN ENE triplex, we screened a library of immobilized small molecules and identified several triplex-binding chemotypes, the tightest of which exhibits micromolar binding affinity. Combined biophysical, biochemical, and computational strategies localized ligand binding to a platform created near a dinucleotide bulge at the base of the triplex. Crystal structures of apo (3.3 Å) and ligand-soaked (2.5 Å) ENE triplexes, which include a stabilizing basal duplex, indicate significant local structural rearrangements within this dinucleotide bulge. MD simulations and a modified nucleoside analog interference technique corroborate the role of the bulge and the base of the triplex in ligand binding. Together with recently discovered small molecules that reduce nuclear MALAT1 lncRNA levels by engaging its ENE triplex, our data supports the potential of targeting RNA triplexes with small molecules.


Seek, Test and Disclose: knowledge of HIV testing and serostatus among high-risk couples in a South African township.
HIV testing and disclosure of results to partners is an important strategy in HIV prevention but is under-researched within heterosexual partnerships. To address this gap, we describe patterns of HIV testing, discrepancies between beliefs and biologically confirmed HIV status of each partner, and characteristics of mutually correct knowledge of HIV status among heterosexual couples in a high-prevalence community. The study recruited 290 high-risk heterosexual couples in stable relationships from a township in Cape Town, South Africa. Male patrons of shebeens (drinking establishments) were approached to participate with their main partner in an intervention designed to reduce substance use, violence and unsafe sex. All participants were tested for HIV at baseline and asked about their partner's past HIV testing and current status. Using the couple as the unit of analysis, we conducted logistic regression to identify partnership and individual characteristics associated with having mutually correct knowledge of partner's HIV status. Half (52%) of women and 41% of men correctly knew whether their partner had ever been tested for HIV. 38% of women, 28% of men and in 17% of couples, both members reported mutually correct knowledge of their partner's HIV status. Correlates of correct knowledge included married/cohabitating (aOR 2.69, 95% CI 1.35 to 5.40), both partners HIV-negative (aOR 3.32 (1.38 to 8.00)), women's acceptance of traditional gender roles (aOR 1.17 (1.01 to 1.40)) and men's relationship satisfaction (aOR 2.22 (1.01 to 4.44)). Findings highlight the need to improve HIV testing uptake among men and to improve HIV disclosure among women in heterosexual partnerships. ClinicalTrials.gov registration NCT01121692.


Comparing a Yoga Class with a Resistance Exercise Class: Effects on Body Satisfaction and Social Physique Anxiety in University Women.
The current study compared a single yoga group exercise class and a resistance group exercise class for their effects on state body satisfaction and social physique anxiety in women. A pretest-posttest design was used. Participants (N = 46) completed both a resistance exercise class and yoga class in a counterbalanced order. Measures of body satisfaction and social physique anxiety were completed immediately before and after each class. A 2 (time) × 2 (class type) repeatedmeasures multiple analysis of variance showed a significant overall Time × Class Type interaction (F2,44 = 5.69, P < .01, η p2 = .21). There was a significant increase in body satisfaction after the yoga class. After both classes, there was a significant decrease in social physique anxiety, but the magnitude of the change was larger after the yoga class than after the resistance class. Both types of exercise class were associated with improvements in body image, but there were greater improvements after the yoga class. This study provided evidence of the positive effects of yoga for reducing state social physique anxiety and increasing state body satisfaction, adding to correlational evidence suggesting that yoga is particularly beneficial for improving body image-related outcomes in women.


Replacement migration, or why everyone is going to have to live in Korea: a fable for our times from the United Nations.
This paper considers international migration in the context of population ageing. In many Western countries, the search for appropriate responses to manage future population ageing and population decline has directed attention to international migration. It seems reasonable to believe that international migrants, mostly of young working age, can supply population deficits created by low birth rates, protect European society and economy from the economic costs of elderly dependency, and provide a workforce to care for the elderly. Particular prominence has been given to this option through the publicity attendant on a report from the UN Population Division in 2000 on 'replacement migration', which has been widely reported and widely misunderstood. Although immigration can prevent population decline, it is already well known that it can only prevent population ageing at unprecedented, unsustainable and increasing levels of inflow, which would generate rapid population growth and eventually displace the original population from its majority position. This paper reviews these arguments in the context of the causes and inevitability of population ageing, with examples mostly based on UK data. It discusses various options available in response to population ageing through workforce, productivity, pensions reform and other means. It concludes that there can be no 'solution' to population ageing, which is to a considerable degree unavoidable. However, if the demographic regime of the United Kingdom continues to be relatively benign, future population ageing can be managed with tolerable inconvenience without recourse to increased immigration for 'demographic' purposes. At present (2001), net immigration to the United Kingdom is already running at record levels and is now the main engine behind UK population and household growth. By itself, population stabilization, or even mild reduction, is probably to be welcomed in the United Kingdom, although the issue has attracted little attention since the 1970s.


Intelligent Imaging in Nuclear Medicine: the Principles of Artificial Intelligence, Machine Learning and Deep Learning.
The emergence of artificial intelligence (AI) in nuclear medicine has occurred over the last 50 years but more recent developments in machine learning (ML) and deep learning (DL) have driven new capabilities of AI in nuclear medicine. In nuclear medicine, the artificial neural network (ANN) is the backbone of ML and DL. The inputs may be radiomic features that have been extracted from the image files or, if using a convolutional neural network (CNN), may be the images themselves. AI in nuclear medicine re-engineers and re-imagines clinical and research capabilities. An understanding of the principles of AI, ML and DL contextualised to nuclear medicine allows richer engagement in clinical and research applications, and capacity for problem solving where required. Simple applications of ML include quality assurance, risk assessment, business analytics and rudimentary classifications. More complex applications of DL for detection, localisation, classification, segmentation, quantitation and radiomic feature extraction using CNNs can be applied to general nuclear medicine, SPECT, PET, CT and MRI. There are also applications of ANNs and ML that allow small datasets (and larger ones) to be analysed in parallel to conventional statistical analysis. AI has assimilated into the clinical and research practice of nuclear medicine with little disruption. The emergence of ML and DL applications, however, has produced a seismic significant shift in the clinical and research landscape that demands at least rudimentary understanding of the principles of AI, ANNs and CNNs among nuclear medicine professionals.


Endoscopic, endoluminal fundoplication for gastroesophageal reflux disease: initial experience and lessons learned.
Several devices have been developed to create an antireflux barrier endoscopically for the treatment of gastroesophageal reflux disease. All have failed to provide long-term symptom relief, were associated with clinically important complications, or were otherwise removed from the market. A new device, the Esophyx (Endogastric Solutions, Redmond, WA), provides the closest approximation experimentally to a standard Belsy fundoplication. This report describes an initial experience with this device. Patients considered candidates for endoscopic fundoplication include those with symptomatic gastroesophageal reflux disease, a small (<2 cm) hiatal hernia, objective pathologic evidence of gastroesophageal reflux disease, and an absence of other esophageal motility disorders. The procedure was conducted under general anesthesia with a surgeon operating the device and an endoscopist operating the gastroscope. H-fasteners were placed from the esophagus to the gastric cardia with the goal of creating an approximately 270-300° fundoplication approximately 3-4 cm in length. Symptom severity was measured with the GERD-HRQL instrument (best possible score 0, worst possible score 50). The patients were followed-up for complications and symptom improvement. In all, 26 patients underwent an attempted endoscopic fundoplication. Two patients could not be completed because of the inability to pass the device. Of the 24 patients who underwent endoscopic fundoplication, 20 had the typical symptoms of gastroesophageal reflux disease, 4 had symptoms of laryngopharyngeal reflux, and 4 had recurrent symptoms after a Nissen fundoplication. There was 1 major complication of a gastric mucosal tear that led to bleeding and the need for a blood transfusion. Nineteen (79%) patients reported satisfaction with their symptom relief. Of those dissatisfied, 2 had symptoms of laryngopharyngeal reflux, 1 had functional heartburn, 1 had associated gastroparesis, and 1 had clear failure with gastroesophageal reflux disease. The median GERD-HRQL score improved from 25 (interquartile range, 19.5-28.5) to 5 (interquartile range, 3-9; P = .0004). Endoscopic fundoplication with the Esophyx device is feasible with satisfactory initial results. Endoscopic fundoplication seems to be best suited for patients with small hiatal hernias and mild-to-moderate typical symptoms; however, subsequent trials are needed to assess the long-term effectiveness of the technique.


Association between long noncoding RNA taurine-upregulated gene 1 and microRNA-377 in vitiligo.
Taurine-upregulated gene 1 (TUG1) is one of the long noncoding RNAs (lncRNAs) that plays a role in melanogenesis. MicroRNA-377 (miRNA-377) is a conserved noncoding RNA that regulates angiogenesis and promotes oxidative stress. Peroxisome proliferator-activated receptors (PPARs) are components of the nuclear hormone receptor superfamily. PPAR-γ activators stimulate melanogenesis. Interleukin (IL)-17 has been implicated in the pathogenesis of several immunological diseases. This work aimed at detecting the expression levels of lncRNA TUG1, miRNA-377, PPAR-γ, and IL-17 among vitiligo subjects and to investigate their possible role in the pathogenesis of vitiligo. This study was conducted on 30 healthy controls and 30 vitiligo patients. LncRNA TUG1 and miRNA-377 were detected in serum by real-time polymerase chain reaction (PCR). Also, expressions of PPAR-γ and IL-17 were assessed in tissue by real-time PCR. LncRNA TUG1 and PPAR-γ levels were significantly downregulated in the vitiligo group compared with the control group. On the other hand, miRNA-377 and IL-17 were significantly upregulated in the vitiligo group compared with the control group. This study demonstrated the dysregulated expressions of lncRNA TUG1 and miRNA-377 in patients with vitiligo suggesting that both contributed to the pathogenesis of vitiligo that might be through PPAR-γ downregulation and IL-17 upregulation.


Detection of antibodies against SARS-CoV-2 spike protein by gold nanospikes in an opto-microfluidic chip.
The ongoing global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to active research in its associated diagnostics and medical treatments. While quantitative reverse transcription polymerase chain reaction (qRT-PCR) is the most reliable method to detect viral genes of SARS-CoV-2, serological tests for specific antiviral antibodies are also important as they identify false negative qRT-PCR responses, track how effectively the patient's immune system is fighting the infection, and are potentially helpful for plasma transfusion therapies. In this work, based on the principle of localized surface plasmon resonance (LSPR), we develop an opto-microfluidic sensing platform with gold nanospikes, fabricated by electrodeposition, to detect the presence and amount of antibodies specific to the SARS-CoV-2 spike protein in 1μL of human plasma diluted in 1mL of buffer solution, within ∼30min. The target antibody concentration can be correlated with the LSPR wavelength peak shift of gold nanospikes caused by the local refractive index change due to the antigen-antibody binding. This label-free microfluidic platform achieves a limit of detection of ∼0.08ng/mL (∼0.5pM), falling under the clinical relevant concentration range. We demonstrate that our opto-microfluidic platform offers a promising point-of-care testing tool to complement standard serological assays and make SARS-CoV-2 quantitative diagnostics easier, cheaper, and faster.


Sodium-assisted formation of binding and traverse conformations of the substrate in a neurotransmitter sodium symporter model.
Therapeutics designed to increase synaptic neurotransmitter levels by inhibiting neurotransmitter sodium symporters (NSSs) classify a strategic approach to treat brain disorders such as depression or epilepsy, however, the critical elementary steps that couple downhill flux of sodium to uphill transport of neurotransmitter are not distinguished as yet. Here we present modelling of NSS member neuronal GAT1 with the substrate γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter. GABA binding is simulated with the occluded conformation of GAT1 homodimer in an explicit lipid/water environment. Simulations performed in the 1-10 ns range of time elucidated persistent formation of halfextended minor and H-bridged major GABA conformations, referred to as binding and traverse conformations, respectively. The traverse GABA conformation was further stabilized by GAT1-bound Na(+)(1). We also observed Na(+)(1) translocation to GAT1-bound Cl(-) as well as the appearance of water molecules at GABA and GAT1-bound Na(+)(2), conjecturing causality. Scaling dynamics suggest that the traverse GABA conformation may be valid for developing substrate inhibitors with high efficacy. The potential for this finding is significant with impact not only in pharmacology but wherever understanding of the mechanism of neurotransmitter uptake is valuable.


The common genetic influence over processing speed and white matter microstructure: Evidence from the Old Order Amish and Human Connectome Projects.
Speed with which brain performs information processing influences overall cognition and is dependent on the white matter fibers. To understand genetic influences on processing speed and white matter FA, we assessed processing speed and diffusion imaging fractional anisotropy (FA) in related individuals from two populations. Discovery analyses were performed in 146 individuals from large Old Order Amish (OOA) families and findings were replicated in 485 twins and siblings of the Human Connectome Project (HCP). The heritability of processing speed was h(2)=43% and 49% (both p<0.005), while the heritability of whole brain FA was h(2)=87% and 88% (both p<0.001), in the OOA and HCP, respectively. Whole brain FA was significantly correlated with processing speed in the two cohorts. Quantitative genetic analysis demonstrated a significant degree to which common genes influenced joint variation in FA and brain processing speed. These estimates suggested common sets of genes influencing variation in both phenotypes, consistent with the idea that common genetic variations contributing to white matter may also support their associated cognitive behavior.


Ileal interposition with sleeve gastrectomy for treatment of type 2 diabetes mellitus.
Combination of laparoscopic ileal interposition (II) with sleeve gastrectomy (SG) is an upcoming procedure, which offers good metabolic improvement and weight reduction without causing significant malabsorption. The objective of this study was to evaluate the results of this novel procedure for control of type 2 diabetes, obesity, hypertension, and related metabolic abnormalities. The II and SG was performed in 43 patients (M:F = 25:18) from February 2008. Participants had a mean age of 47.2 ± 8.2 years (range 29-66 years), mean duration of diabetes of 10.1 ± 9.2 years (range 1-32 years), and mean preoperative body mass index (BMI) of 33.2 ± 7.8 kg/m2. All patients had poorly controlled type 2 diabetes mellitus (DM) [mean glycated hemoglobin (HbA1C) 9.6 ± 2.1%] despite use of oral hypoglycemic agents (OHAs) and/or insulin. Thirty (70%) patients had hypertension, 20 (46%) had dyslipidemia, and 18 (42%) had significant microalbuminuria. The primary outcome was remission of diabetes (HbA1C < 6.5% without OHAs/insulin) and the secondary outcomes were reduction in antidiabetic agent requirement and components of metabolic syndrome. Mean follow-up was for 20.2 ± 8.6 months (range 4-40 months). Postoperatively, glycemic parameters (fasting and post-lunch blood sugar, HbA1C improved in all patients (P < 0.05) at all intervals. Twenty (47%) patients had remission in diabetes and the remaining patients showed significantly decreased OHA requirement. All patients had weight loss between 15 and 30% (P < 0.05). Twenty-seven (90%) patients had remission in hypertension. At 3 years, the mean fall in HbA1C (34%) was more than reduction in BMI (25%). There was a declining trend in lipids and microalbuminuria postoperatively, though it was significant for microalbuminuria only. The laparoscopic II with SG seems to be a promising procedure for control of type 2 DM, hypertension, weight reduction, and associated metabolic abnormalities. A multicenter study with larger number of patients and a longer follow-up period is needed to substantiate our preliminary findings.


Nursing competencies for family-centred care in the hospital setting: A multinational Q-methodology study.
to identify: (1) nursing competencies for FCC in a hospital setting; and (2) to explore perspectives on these competencies among Dutch and Australian professionals including lecturers, researchers, Registered Nurses and policy makers. A multinational cross-sectional study using Q-methodology. First, an integrative review was carried out to identify known competencies regarding FCC and to develop the Q-set (search up to July 2018). Second, purposive sampling was used to ensure stakeholder involvement. Third, participants sorted the Q-set using a web-based system between May and August 2019. Lastly, the data were analysed using a by-person factor analysis. The commentaries on the five highest and lowest ranked competencies were thematically analysed. The integrative review identified 43 articles from which 72 competencies were identified. In total 69 participants completed the Q-sorting. We extracted two factors with an explained variance of 24%. The low explained variance hampered labelling. Based on a post-hoc qualitative analysis, four themes emerged from the competencies that were considered most important, namely: (a) believed preconditions for FCC; (b) promote a partnership between nurses, patients and families; (c) be a basic element of nursing; and (d) represent a necessary positive attitude and strong beliefs of the added value of FCC. Three themes appeared from the competencies that were considered least important because they: (a) were not considered a specific nursing competency; (b) demand a multidisciplinary approach; or (c) require that patients and families take own responsibility. Among healthcare professionals, there is substantial disagreement on which nursing competencies are deemed most important for FCC. Our set of competencies can be used to guide education and evaluate practicing nurses in hospitals. These findings are valuable to consider different views on FCC before implementation of new FCC interventions into nursing practice.


Label-free imaging of lipophilic bioactive molecules during lipid digestion by multiplex coherent anti-Stokes Raman scattering microspectroscopy.
The digestion and absorption of lipophilic, bioactive molecules such as lipids, physiologically active nutrients (nutraceuticals), and drugs play a crucial role in human development and health. These molecules are often delivered in lipid droplets. Currently, the kinetics of digestion of these lipid droplets is followed by in vitro models that simulate gastrointestinal conditions, while phase changes within the lipid droplets are observed by light or electron microscopy. However real-time, spatially resolved information about the local chemical composition and phase behavior inside the oil droplet is not accessible from these approaches. This information is essential as the surface and phase behavior determine the local distribution of molecules in the oil droplets and thus may influence the rate of uptake, for example, by impairing the effective transfer of bioactive molecules to intestinal cells. We demonstrate the capability of multiplex coherent anti-Stokes Raman scattering (CARS) microspectroscopy to image the digestion process non-invasively, with submicrometer resolution, millimolar sensitivity, and without the need for labeling. The lipolysis of glyceryl trioleate emulsion droplets by porcine pancreatic lipase is imaged, and the undigested oil and the crystalline lipolytic products are distinguished by their different vibrational signatures. The digestion of droplets containing the phytosterol analogue ergosterol is also probed, and the crystals are observed to dissolve into the lipolytic products. The lipophilic drug progesterone and Vitamin D(3) are dissolved in glyceryl trioctanoate emulsion droplets, and the local concentration is mapped with millimolar sensitivity. The bioactive molecules are observed to concentrate within the droplets as the oil is hydrolyzed. This observation is ascribed to the low solubility of these molecules in the lipolytic products for this system. Neither the type of bioactive molecule nor the initial radius of the emulsion droplet had a large effect upon the rate of digestion under these conditions; lipolysis of the triglyceride by pancreatic lipase appears insensitive to the type of bioactive molecule in solution. These findings shed important new light on lipid digestion and open new possibilities for the chemical visualization of lipid digestion and phase changes in lipid droplets containing bioactive molecules, which in combination with other existing techniques will provide a full picture of this complex physicochemical process.


Ecological risk assessment issues identified during the U.S. Environmental Protection Agency's examination of risk assessment practices.
Recently, the U.S. Environmental Protection Agency examined its current risk-assessment principles and practices. As part of the examination, aspects of ecological risk-assessment practices were reviewed. Several issues related to ecological risk assessment were identified, including the use of organism-level versus population-level attributes to characterize risk, the possible opportunities associated with the increased use of probabilistic approaches for ecological risk assessment, and the notion of conservatism in estimating risks. The agency examination provides an understanding of current practices and is intended to begin a dialogue in which the risk assessment community can engage in addressing the identified issues to improve and enhance ecological risk assessment.


A well-constrained estimate for the timing of the salmonid whole genome duplication reveals major decoupling from species diversification.
Whole genome duplication (WGD) is often considered to be mechanistically associated with species diversification. Such ideas have been anecdotally attached to a WGD at the stem of the salmonid fish family, but remain untested. Here, we characterized an extensive set of gene paralogues retained from the salmonid WGD, in species covering the major lineages (subfamilies Salmoninae, Thymallinae and Coregoninae). By combining the data in calibrated relaxed molecular clock analyses, we provide the first well-constrained and direct estimate for the timing of the salmonid WGD. Our results suggest that the event occurred no later in time than 88 Ma and that 40-50 Myr passed subsequently until the subfamilies diverged. We also recovered a Thymallinae-Coregoninae sister relationship with maximal support. Comparative phylogenetic tests demonstrated that salmonid diversification patterns are closely allied in time with the continuous climatic cooling that followed the Eocene-Oligocene transition, with the highest diversification rates coinciding with recent ice ages. Further tests revealed considerably higher speciation rates in lineages that evolved anadromy--the physiological capacity to migrate between fresh and seawater--than in sister groups that retained the ancestral state of freshwater residency. Anadromy, which probably evolved in response to climatic cooling, is an established catalyst of genetic isolation, particularly during environmental perturbations (for example, glaciation cycles). We thus conclude that climate-linked ecophysiological factors, rather than WGD, were the primary drivers of salmonid diversification.


Hypoxic enhancement of exosome release by breast cancer cells.
Exosomes are nanovesicles secreted by tumour cells which have roles in paracrine signalling during tumour progression, including tumour-stromal interactions, activation of proliferative pathways and bestowing immunosuppression. Hypoxia is an important feature of solid tumours which promotes tumour progression, angiogenesis and metastasis, potentially through exosome-mediated signalling. Breast cancer cell lines were cultured under either moderate (1% O2) or severe (0.1% O2) hypoxia. Exosomes were isolated from conditioned media and quantitated by nanoparticle tracking analysis (NTA) and immunoblotting for the exosomal protein CD63 in order to assess the impact of hypoxia on exosome release. Hypoxic exosome fractions were assayed for miR-210 by real-time reverse transcription polymerase chain reaction and normalised to exogenous and endogenous control genes. Statistical significance was determined using the Student T test with a P value of < 0.05 considered significant. Exposure of three different breast cancer cell lines to moderate (1% O2) and severe (0.1% O2) hypoxia resulted in significant increases in the number of exosomes present in the conditioned media as determined by NTA and CD63 immunoblotting. Activation of hypoxic signalling by dimethyloxalylglycine, a hypoxia-inducible factor (HIF) hydroxylase inhibitor, resulted in significant increase in exosome release. Transfection of cells with HIF-1α siRNA prior to hypoxic exposure prevented the enhancement of exosome release by hypoxia. The hypoxically regulated miR-210 was identified to be present at elevated levels in hypoxic exosome fractions. These data provide evidence that hypoxia promotes the release of exosomes by breast cancer cells, and that this hypoxic response may be mediated by HIF-1α. Given an emerging role for tumour cell-derived exosomes in tumour progression, this has significant implications for understanding the hypoxic tumour phenotype, whereby hypoxic cancer cells may release more exosomes into their microenvironment to promote their own survival and invasion.


Leaf metabolic signatures induced by real and simulated herbivory in black mustard (Brassica nigra).
The oxylipin methyl jasmonate (MeJA) is a plant hormone active in response signalling and defence against herbivores. Although MeJA is applied experimentally to mimic herbivory and induce plant defences, its downstream effects on the plant metabolome are largely uncharacterized, especially in the context of primary growth and tissue-specificity of the response. We investigated the effects of MeJA-simulated and real caterpillar herbivory on the foliar metabolome of the wild plant Brassica nigra and monitored the herbivore-induced responses in relation to leaf ontogeny. As single or multiple herbivory treatments, MeJA- and mock-sprayed plants were consecutively exposed to caterpillars or left untreated. Gas chromatography (GC) and liquid chromatography (LC) time-of-flight mass-spectrometry (TOF-MS) were combined to analyse foliar compounds, including central primary and specialized defensive plant metabolites. Plant responses were stronger in young leaves, which simultaneously induced higher chlorophyll levels. Both MeJA and caterpillar herbivory induced similar, but not identical, accumulation of tricarboxylic acids (TCAs), glucosinolates (GSLs) and phenylpropanoids (PPs), but only caterpillar feeding led to depletion of amino acids. MeJA followed by caterpillars caused higher induction of defence compounds, including a three-fold increase in the major defence compound allyl-GSL (sinigrin). When feeding on MeJA-treated plants, caterpillars gained less weight indicative of the reduced host-plant quality and enhanced resistance. The metabolomics approach showed that plant responses induced by herbivory extend beyond the regulation of defence metabolism and are tightly modulated throughout leaf development. This leads to a new understanding of the plant metabolic potential that can be exploited for future plant protection strategies.


Biopersistence of man-made vitreous silicate fibers in the human lung.
There is now a substantial body of experimental data on the pulmonary biopersistence of man-made vitreous silicate fibers (MMVSF), but human data are seriously lacking. Our knowledge in this field is essentially limited to a few reports of measurements of fibers retained in lung tissue samples taken at autopsy from workers manufacturing these products. Three types of exposure were studied: fibrous glass, mineral wool, and refractory ceramic fibers. Overall, the available data do not provide evidence for substantial long-term retention of fibers in the human lung after occupational exposure to MMVSF dusts. A word of caution, however; the amount of data supporting the previous statement is much greater for fibrous glass than for either mineral wool or refractory ceramic fibers. There is no human data on the key question of the kinetics of pulmonary clearance of inhaled MMVSF.


Low dosage tricyclic antidepressants for depression.
Tricyclic antidepressants are still extensively prescribed worldwide. Evidence for the recommended dosage of tricyclics, however, is poor. To compare the effects and side effects of low dosage tricyclic antidepressants with placebo and with standard dosage tricyclics in acute phase treatment of depression. Electronic search of the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), incorporating results of group searches of MEDLINE (1966-), EMBASE (1980-), CINAHL (1982-), PsycLIT (1974-), PSYNDEX (1977-) and LILACS (1982-1999) and hand searches of major psychiatric and medical journals. Reference search and SciSearch of the identified studies. Personal contact with authors of significant papers. All randomised controlled trials 1) comparing low dosage TCA (=< 100 mg/d on average at the end of trial) with placebo or 2) comparing low and standard dosages of the same TCA, in acute phase treatment of depressive disorder Two independent reviewers examined eligibility of the identified studies, and extracted data for outcomes at 1 week, 2 weeks, 4 weeks, 6-8 weeks and later. Main outcome measures were relative risk of response in depression (random effects model), according to the original authors' definition but usually defined as 50% or greater reduction in severity of depression according to the last-observation-carried-forward intention-to-treat method, and relative risks of overall dropouts and dropouts due to side effects. Other outcome measures included worst-case-scenario intention-to-treat analysis of response as defined above (in which dropouts were considered non-responders in the active treatment group and as responders in the comparison group), and standardised weighted mean scores of continuous depression severity scales (usually calculated by last-observation-carried-forward method). 35 studies (2013 participants) compared low dosage tricyclics with placebo, and six studies (551 participants) compared low dosage tricyclics with standard dosage tricyclics. Low dosage tricyclics, mostly between 75 and 100 mg/day, were 1.65 (95% confidence interval 1.36 to 2.0) and 1.47 (1.12 to 1.94) times more likely than placebo to bring about response at 4 weeks and 6-8 weeks, respectively. Standard dosage tricyclics failed, however, to bring about more response but produced more dropouts due to side effects than low dosage tricyclics. Treatment of depression in adults with low dose tricyclics is justified. However, more rigorous studies are needed to definitively establish the relative benefits and harms of varying dosages.


Matrix metalloproteinase-1 and -9 promoter polymorphisms are not associated with an increased risk of uterine leiomyomas in a Japanese population.
Matrix metalloproteinases (MMPs) play an important role in modeling and remodeling the extracellular matrix in leiomyomas. Hence, we investigated whether associations exist between leiomyomas and promoter polymorphisms in the MMP-1 and MMP-9 genes in a Japanese population. We compared the distribution of polymorphisms in the promoter regions of MMP-1 (-1607 1G/2G) and MMP-9 (-1562 C/T) in 267 leiomyoma patients and 184 control patients using polymerase chain reaction-fragment-length polymorphism (PCR-RFLP) analysis. The allele frequencies of the MMP-1 -1607 2G and MMP-9 -1562 T polymorphisms were 74.6% and 18.6% in leiomyoma patients, and 71.3% and 18.6% in control patients, respectively. No significant differences in allele frequencies or genotype distributions were found between leiomyoma and control patients. Moreover, no associations were found between MMP-1 and MMP-9 genotypes and leiomyoma size or a family history of the condition. These findings suggest that MMP-1 and MMP-9 promoter polymorphisms are unlikely to be associated with an increased risk of uterine leiomyomas in Japanese women.


Ducks: the "Trojan horses" of H5N1 influenza.
Wild ducks are the main reservoir of influenza A viruses that can be transmitted to domestic poultry and mammals, including humans. Of the 16 hemagglutinin (HA) subtypes of influenza A viruses, only the H5 and H7 subtypes cause highly pathogenic (HP) influenza in the natural hosts. Several duck species are naturally resistant to HP Asian H5N1 influenza viruses. These duck species can shed and spread virus from both the respiratory and intestinal tracts while showing few or no disease signs. While the HP Asian H5N1 viruses are 100% lethal for chickens and other gallinaceous poultry, the absence of disease signs in some duck species has led to the concept that ducks are the "Trojan horses" of H5N1 in their surreptitious spread of virus. An important unresolved issue is whether the HP H5N1 viruses are maintained in the wild duck population of the world. Here, we review the ecology and pathobiology of ducks infected with influenza A viruses and ducks' role in the maintenance and spread of HP H5N1 viruses. We also identify the key questions about the role of ducks that must be resolved in order to understand the emergence and control of pandemic influenza. It is generally accepted that wild duck species can spread HP H5N1 viruses, but there is insufficient evidence to show that ducks maintain these viruses and transfer them from one generation to the next.


Can teenagers with traumatic brain injury use Internet chatrooms? A systematic review of the literature and the Internet.
To systematically review literature and electronic resources that address the topic of chatroom use of teenagers with and without traumatic brain injury (TBI). Electronic databases and websites on the Internet were searched up to and including 25 June 2009, using terms relating to chatroom use of teenagers without and with TBI. A separate search was conducted on speechBITETM (www.speechbite.com ), using fields specific to target area, intervention and population. Literature and websites were included if they contained target search terms and were relevant to the topic of chatroom use of teenagers. A total of 46 sources from database searches and 66 websites from Internet searches were included in this systematic review. Most database sources were level IV evidence studies and mainly addressed chatroom and Internet use of typically-developing teenagers. Websites contained many brain injury information pages and links to chatrooms, as well as references to journal articles and books concerning chatroom use. Due to the lack of literature in the area of chatroom use of teenagers with TBI, there is potential to expand on existing literature and Internet resources to enable teenagers with TBI to access, participate and use this forum for social interaction and meaningful communication with peers.


Association Between Therapeutic Hypothermia and Survival After In-Hospital Cardiac Arrest.
Therapeutic hypothermia is used for patients following both out-of-hospital and in-hospital cardiac arrest. However, randomized trials on its efficacy for the in-hospital setting do not exist, and comparative effectiveness data are limited. To evaluate the association between therapeutic hypothermia and survival after in-hospital cardiac arrest. In this cohort study, within the national Get With the Guidelines-Resuscitation registry, 26 183 patients successfully resuscitated from an in-hospital cardiac arrest between March 1, 2002, and December 31, 2014, and either treated or not treated with hypothermia at 355 US hospitals were identified. Follow-up ended February 4, 2015. Induction of therapeutic hypothermia. The primary outcome was survival to hospital discharge. The secondary outcome was favorable neurological survival, defined as a Cerebral Performance Category score of 1 or 2 (ie, without severe neurological disability). Comparisons were performed using a matched propensity score analysis and examined for all cardiac arrests and separately for nonshockable (asystole and pulseless electrical activity) and shockable (ventricular fibrillation and pulseless ventricular tachycardia) cardiac arrests. Overall, 1568 of 26 183 patients with in-hospital cardiac arrest (6.0%) were treated with therapeutic hypothermia; 1524 of these patients (mean [SD] age, 61.6 [16.2] years; 58.5% male) were matched by propensity score to 3714 non-hypothermia-treated patients (mean [SD] age, 62.2 [17.5] years; 57.1% male). After adjustment, therapeutic hypothermia was associated with lower in-hospital survival (27.4% vs 29.2%; relative risk [RR], 0.88 [95% CI, 0.80 to 0.97]; risk difference, -3.6% [95% CI, -6.3% to -0.9%]; P = .01), and this association was similar (interaction P = .74) for nonshockable cardiac arrest rhythms (22.2% vs 24.5%; RR, 0.87 [95% CI, 0.76 to 0.99]; risk difference, -3.2% [95% CI, -6.2% to -0.3%]) and shockable cardiac arrest rhythms (41.3% vs 44.1%; RR, 0.90 [95% CI, 0.77 to 1.05]; risk difference, -4.6% [95% CI, -10.9% to 1.7%]). Therapeutic hypothermia was also associated with lower rates of favorable neurological survival for the overall cohort (hypothermia-treated group, 17.0% [246 of 1443 patients]; non-hypothermia-treated group, 20.5% [725 of 3529 patients]; RR, 0.79 [95% CI, 0.69 to 0.90]; risk difference, -4.4% [95% CI, -6.8% to -2.0%]; P < .001) and for both rhythm types (interaction P = .88). Among patients with in-hospital cardiac arrest, use of therapeutic hypothermia compared with usual care was associated with a lower likelihood of survival to hospital discharge and a lower likelihood of favorable neurological survival. These observational findings warrant a randomized clinical trial to assess efficacy of therapeutic hypothermia for in-hospital cardiac arrest.


Acetic acid wash and chemiluminescent illumination as an adjunct to conventional oral soft tissue examination for the detection of dysplasia: a pilot study.
Population-based oral cancer screening appears to be a promising health promotion strategy (especially in high-risk individuals) with significant increases in quality-adjusted life years saved. However, the current protocol, conventional visual inspection, and palpation of oral soft tissues for the early detection of pre-malignant or malignant changes, appears to be deficient. The adjunctive application of technology to highlight such lesions may increase the diagnostic yield. The purpose of this pilot study was to collect data, which might support the hypothesis that oral soft tissues exhibit features similar to the cervical epithelium following an acetic acid wash and visual inspection under chemiluminescent illumination. The data provides strong evidence to support the hypothesis. Epithelium with hyperkeratinization, hyperparakeratinization, and/or chronic inflammatory infiltrate reflects the diffuse, low-level, blue-white chemiluminescent light more strongly and appears amplified. Similarly, epithelium with an altered nuclear-cytoplasmic ratio also reflects the diffuse, low-level, blue-white chemiluminescent light. In such cases, the lesions become clinically discernible and appear "acetowhite." Large-scale studies are required to further refine issues related to the selectivity and specificity of the technology.


Soybean FGAM synthase promoters direct ectopic nematode feeding site activity.
Soybean cyst nematode (SCN) resistance in soybean is a complex oligogenic trait. One of the most important nematode resistance genes, rhg1, has been mapped to a distal region of molecular linkage group G in soybean. A simplified genetic system to identify soybean genes with modified expression in response to SCN led to the identification of several genes within the nematode feeding sites. The genes were mapped to reveal their linkage relationship to known QTLs associated with soybean cyst nematode (SCN) resistance. One candidate, a phosphoribosyl formyl glycinamidine (FGAM) synthase (EC 22.214.171.124) gene, mapped to the same genomic interval as the major SCN resistance gene rhg1 within linkage group G. Isolation of FGAM synthase from a soybean bacterial artificial chromosome (BAC) library revealed two highly homologous paralogs. The genes appeared to be well conserved between bacteria and humans. Promoter analysis of the two soybean homologs was carried out with the Arabidopsis thaliana - Heterodera schachtii system to investigate gene response to nematode feeding. The two promoters and their derived deletion constructions effected green fluorescent protein (GFP) expression within nematode feeding sites. The 1.0-kb promoter sequence immediately adjacent to the translation start site was sufficient to direct expression of GFP within syncytia. A wound-inducible element and a floral organ expression sequence were also identified within these promoters. Although a nematode-responsive element could not be identified, the observed expression of GFP within feeding sites supports the hypothesis that plant gene expression is redirected within feeding sites to benefit the parasite.


Pediatric pelvic fractures: a marker for injury severity.
Pelvic fractures comprise a small number of annual Level I pediatric trauma center admissions. This is a review of the University of Chicago Level I Pediatric Trauma Center experience with pediatric pelvic fractures. This is a retrospective review of the University of Chicago Level I Pediatric Trauma Center experience with pediatric pelvic fractures during the 12-year period from 1992 to 2004. From 1992 to 2004, there were 2850 pediatric trauma admissions. Thirteen patients were identified with pelvic fractures; seven were boys and six were girls. The average age was 8 years old. The mechanism of injury in all cases was motor vehicle related; 11 patients (87%) sustained pedestrian-motor vehicle crashes. According to the Torode and Zeig classification system, type III fractures occurred in eight patients (62%) and type IV fractures occurred in six patients (31%). Associated injuries occurred in eight patients (62%). Seven of these patients (88%) had associated injuries involving two or more organ systems. Of the associated injuries, additional orthopedic injuries were the most common, occurring in 62 per cent of our patients. Neurological injuries occurred in 54 per cent of patients, vascular injuries in 39 per cent, pulmonary injuries in 31 per cent, and genitourinary injuries in 15 per cent. Five patients (38%) were treated operatively; only two patients underwent operative management directly related to their pelvic fracture. The remaining three patients underwent operative management of associated injuries. The mortality rate was 0 per cent. Although pelvic fractures are an uncommon injury in pediatric trauma patients, the morbidity associated with these injuries can be profound. The majority of pelvic fractures in children are treated nonoperatively, however, more than one-half of these patients have concomitant injuries requiring operative management. When evaluating and treating pediatric pelvic fractures, a systematic multidisciplinary approach must be taken to evaluate and prioritize the pelvic fracture and the associated injuries.


Large goiter and multiple rib tumors.
We report an interesting case of a 47-yr-old who had a large goiter and multiple rib tumors. The patient was initially suspected of having thyroid cancer, which had metastasized on the ribs, based on imaging studies. However, laboratory tests revealed a high level of ionized calcium and parathyroid hormone (PTH). The large goiter was diagnosed as having parathyroid tumors owing to the high level of PTH in the tissue fluid. The biopsy specimen from a rib tumor was diagnosed as containing brown tumors associated with primary hyperparathyroidism (PHP). The patient also had prolactinoma and pancreatic gastrinoma. Her daughter had both prolactinoma and PHP, and her brother and her father had PHP. Thus, the patient was diagnosed as having multiple endocrine neoplasia type 1.


Induction and Maintenance of Systemic Acquired Resistance by Acibenzolar-S-Methyl in Three Cultivated Tobacco Types.
Induction and maintenance of systemic acquired resistance (SAR) in 'N' gene containing burley, flue-cured, and oriental tobacco cultivars were assessed by monitoring decreases in the number of local lesions caused by Tobacco mosaic virus (TMV) following treatment with acibenzolar-S-methyl (ASM). Leaf samples were collected from lower, middle, and top positions on seedlings at 3-day intervals over 21 days following ASM treatment and subsequent inoculation with TMV under laboratory conditions. Local lesion number for each leaf was recorded 7 days postinoculation. Reductions in TMV local lesion numbers on ASM-treated versus nontreated tobacco varied over time, and differed for each tobacco type. Based on reduced local lesion numbers, SAR was induced in burley and flue-cured tobacco by 3 and 6 days postinoculation, respectively, while oriental tobacco responded by 9 days. SAR was maintained in burley tobacco from 3 to 9 days after ASM application, and from 9 to 15 days after application in oriental tobacco. ASM treatment reduced local lesion numbers in flue-cured tobacco significantly at 6, 12, and 21 days postapplication, but not at 15 and 18 days after treatment. The SAR response was similar among lower, middle, and top leaves with no effect of ASM on response by leaf position, although TMV local lesion numbers were greater on lower leaves than on middle and top leaves 6 days after treatment, but significantly less on lower leaves 18 days after treatment compared to middle and top leaves.


Oropouche virus transmission in the Amazon River basin of Peru.
Seroepidemiologic studies were conducted to determine the prevalence of Oropouche (ORO) viral antibody, risk factors, and the incidence of infection among residents of the Amazon region of Peru. Blood samples, as well as demographic, cultural, and medical history data, were collected from residents in a sector of the city of Iquitos and in an adjacent rural and three neotropical rain forest communities. Blood specimens were obtained approximately one year later from a cohort of the same study subjects who were negative for ORO antibody on the initial cross-sectional survey. Sera were tested for ORO IgG antibody by an enzyme-linked immunosorbent assay. Antibody prevalences were 35% for residents of the urban population, 24-46% for the forest communities, and 18% for the rural community. Antibody prevalence increased with age, and subjects who were seropositive were significantly (P = 0.001) older (mean = 33 years) than the seronegative subjects (mean = 15 years). Multivariate analysis revealed that only age, urban and forest residence, and occupation as a farmer or housekeeper remained significantly associated with seropositivity. Seroconversion data for the same populations one year later demonstrated evidence of ORO viral infection among 28% of the residents in the rural community and 2% or less in the forest and urban communities. Oropouche virus infection was significantly associated with older age (P = 0.04) in the rural community (P < 0.001). These data support prior evidence of ORO viral infection among residents of Iquitos and surrounding villages and suggest that transmission of this virus occurs continuously in the population of this area of the Amazon basin.


Autism and genius: is there a link? The involvement of central brain loops and hypotheses for functional testing.
Mental processing is the product of the huge number of synaptic interactions that occur in the brain. It is easier to understand how brain functions can deteriorate than how they might be boosted. Lying at the border between the humanities, cognitive science and neurophysiology, some mental diseases offer new angles on this problematic issue. Despite their social deficits, autistic subjects can display unexpected and extraordinary skills in numerous fields, including music, the arts, calculation and memory. The advanced skills found in a subgroup of people with autism may be explained by their special mental functioning, in particular by their weak central coherence, one of the pivotal characteristics of the disorder. As a result of the increasing interest in autistic talent, there has recently emerged a tendency to screen any eccentric artist or scientist for traits of the autistic spectrum. Following this trend, we analyze the eccentricity of the popular pianist Glenn Gould and briefly discuss the major functional hypotheses on autistic hyperfunctioning, advancing proposals for functional testing. In particular, the potential involvement of rhythm-entrained systems and cerebro-cerebellar loops opens up new perspectives for the investigation of autistic disorders and brain hyperfunctioning.


Setting of import tolerances for azoxystrobin in mangoes and oil palm fruits.
In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Syngenta Crop Protection AG submitted a request to the competent national authority in Austria to set an import tolerance for the active substance azoxystrobin in mangoes and oil palm fruits imported from Brazil and Colombia, respectively. The data submitted in support of the request were found to be sufficient to derive maximum residue level (MRL) proposals for mangoes and oil palm fruits. Adequate analytical methods for enforcement are available to control the residues of azoxystrobin on the commodities under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg. Based on the risk assessment results, noting that an acute risk assessment was not deemed necessary for azoxystrobin, EFSA concluded that the long-term intake of residues resulting from the uses of azoxystrobin according to the reported agricultural practices is unlikely to present a risk to consumer health.


Applications of MALDI-TOF mass spectrometry in clinical proteomics.
The development of precision medicine requires advanced technologies to address the multifactorial disease stratification and to support personalized treatments. Among omics techniques, proteomics based on Mass Spectrometry (MS) is becoming increasingly relevant in clinical practice allowing a phenotypic characterization of the dynamic functional status of the organism. From this perspective, Matrix Assisted Laser Desorption Ionization Time of Flight (MALDI-TOF) MS is a suitable platform for providing a high-throughput support to clinics. Areas covered: This review aims to provide an updated overview of MALDI-TOF MS applications in clinical proteomics. The most relevant features of this analysis have been discussed, highlighting both pre-analytical and analytical factors that are crucial in proteomics studies. Particular emphasis is placed on biofluids proteomics for biomarkers discovery and on recent progresses in clinical microbiology, drug monitoring, and minimal residual disease (MRD). Expert commentary: Despite some analytical limitations, the latest technological advances together with the easiness of use, the low time and low cost consuming and the high throughput are making MALDI-TOF MS instruments very attractive for the clinical practice. These features offer a significant potential for the routine of the clinical laboratory and ultimately for personalized medicine.


Perceiving polarization with the naked eye: characterization of human polarization sensitivity.
Like many animals, humans are sensitive to the polarization of light. We can detect the angle of polarization using an entoptic phenomenon called Haidinger's brushes, which is mediated by dichroic carotenoids in the macula lutea. While previous studies have characterized the spectral sensitivity of Haidinger's brushes, other aspects remain unexplored. We developed a novel methodology for presenting gratings in polarization-only contrast at varying degrees of polarization in order to measure the lower limits of human polarized light detection. Participants were, on average, able to perform the task down to a threshold of 56%, with some able to go as low as 23%. This makes humans the most sensitive vertebrate tested to date. Additionally, we quantified a nonlinear relationship between presented and perceived polarization angle when an observer is presented with a rotatable polarized light field. This result confirms a previous theoretical prediction of how uniaxial corneal birefringence impacts the perception of Haidinger's brushes. The rotational dynamics of Haidinger's brushes were then used to calculate corneal retardance.We suggest that psychophysical experiments, based upon the perception of polarized light, are amenable to the production of affordable technologies for self-assessment and longitudinal monitoring of visual dysfunctions such as age-related macular degeneration.


Free-hand placement of iliac screws for spinopelvic fixation based on anatomical landmarks: technical note.
The placement of iliac screws is a biomechanically sound method for the stabilization of long multi-segment lumbar constructs. Traditional techniques for the placement of iliac screws often involve either substantial iliac muscle dissection for visualization of screw trajectory based on bony landmarks, or alternatively the use of intra-operative imaging to visualize these landmarks and guide screw placement. We describe an alternative free-hand method of iliac screw placement, one that needs neither significant muscle dissection nor intra-operative imaging. We performed this technique in 10 consecutive patients. Patient demographics, spinal pathology, post-operative complications, and screw hardware characteristics are described. We have successfully used this technique for the placement 20 iliac screws based on anatomic landmarks in 10 consecutive patients. There were no cortical breeches of the ileum and no penetrations into the acetabulum on post-operative imaging. There were no instances of hardware failure. Two patients developed deep vein thromboses after surgery, 1 had a pulmonary embolism. Based on our limited experience to date, free-hand placement of iliac screws is both easy to perform and safe for the patient. Further study and validation using this technique is warranted.


Effects of Sapindus mukorossi Seed Oil on Skin Wound Healing: In Vivo and in Vitro Testing.
Sapindus mukorossi seed oil is commonly used as a source for biodiesel fuel. Its phytochemical composition is similar to the extracted oil from Sapindus trifoliatus seeds, which exhibit beneficial effects for skin wound healing. Since S. mukorossi seed shows no cyanogenic property, it could be a potential candidate for the treatment of skin wounds. Thus, we evaluated the effectiveness of S. mukorossi seed oil in the treatment of skin wounds. We characterized and quantified the fatty acids and unsaponifiable fractions (including β-sitosterol and δ-tocopherol) contained in S. mukorossi seed-extracted oil by GC-MS and HPLC, respectively. Cell proliferation and migratory ability were evaluated by cell viability and scratch experiments using CCD-966SK cells treated with S. mukorossi oil. The anti-inflammatory effects of the oil were evaluated by measuring the nitric oxide (NO) production in lipopolysaccharide-treated RAW 264.7 cells. Antimicrobial activity tests were performed with Propionibacterium acnes, Staphylococcus aureus, and Candida albicans using a modified Japanese Industrial Standard procedure. Uniform artificial wounds were created on the dorsum of rats. The wounds were treated with a carboxymethyl cellulose (CMC)/hyaluronic acid (HA)/sodium alginate (SA) hydrogel for releasing the S. mukorossi seed oil. The wound sizes were measured photographically for 12 days and were compared to wounds covered with analogous membranes containing a saline solution. Our results showed that the S. mukorossi seed oil used in this study contains abundant monounsaturated fatty acids, β-sitosterol, and δ-tocopherol. In the in vitro tests, S. mukorossi seed oil prompted cell proliferation and migration capability. Additionally, the oil had significant anti-inflammatory and anti-microbial activities. In the in vivo animal experiments, S. mukorossi seed oil-treated wounds revealed acceleration of sequential skin wound healing events after two days of healing. The size of oil-treated wound decreased to half the size of the untreated control after eight days of healing. The results suggest that S. mukorossi seed oil could be a potential source for promoting skin wound healing.


Microstructural and compositional contributions towards the mechanical behavior of aging human bone measured by cyclic and impact reference point indentation.
The assessment of fracture risk often relies primarily on measuring bone mineral density, thereby accounting for only a single pathology: the loss of bone mass. However, bone's ability to resist fracture is a result of its biphasic composition and hierarchical structure that imbue it with high strength and toughness. Reference point indentation (RPI) testing is designed to directly probe bone mechanical behavior at the microscale in situ, although it remains unclear which aspects of bone composition and structure influence the results at this scale. Therefore, our goal in this study was to investigate factors that contribute to bone mechanical behavior measured by cyclic reference point indentation, impact reference point indentation, and three-point bending. Twenty-eight female cadavers (ages 57-97) were subjected to cyclic and impact RPI in parallel at the unmodified tibia mid-diaphysis. After RPI, the middiaphyseal tibiae were removed, scanned using micro-CT to obtain cortical porosity (Ct.Po.) and tissue mineral density (TMD), then tested using three-point bending, and lastly assayed for the accumulation of advanced glycation end-products (AGEs). Both the indentation distance increase from cyclic RPI (IDI) and bone material strength index from impact RPI (BMSi) were significantly correlated with TMD (r=-0.390, p=0.006; r=0.430, p=0.002; respectively). Accumulation of AGEs was significantly correlated with IDI (r=0.281, p=0.046), creep indentation distance (CID, r=0.396, p=0.004), and BMSi (r=-0.613, p<0.001). There were no significant relationships between tissue TMD or AGEs accumulation with the quasi-static material properties. Toughness decreased with increasing tissue Ct.Po. (r=-0.621, p<0.001). Other three-point bending measures also correlated with tissue Ct.Po. including the bending modulus (r=-0.50, p<0.001) and ultimate stress (r=-0.56, p<0.001). The effects of Ct.Po. on indentation were less pronounced with IDI (r=0.290, p=0.043) and BMSi (r=-0.299, p=0.037) correlated modestly with tissue Ct.Po. These results suggest that RPI may be sensitive to bone quality changes relating to collagen.


Hematological features of patients with myelodysplastic syndromes associated with a chromosome 5q deletion.
The hematological and clinical features of 26 patients with myelodysplasia and a chromosome 5q deletion in the bone marrow are presented. We have examined the relationship of French-American-British Co-operative Group (FAB) 1982 classification and bone marrow karyotype at diagnosis with patient outcome and the presence or absence of the classical features of the 5q-syndrome. Those patients classified as refractory anemia (RA) with no additional karyotypic abnormalities have the typical features of the 5q-syndrome and a good prognosis. None of the patients in this group transformed to acute leukemia during the period of follow-up. Patients with either refractory anemia and excess blasts (RAEB) or additional karyotypic abnormalities show many of the hematologic features of the 5q-syndrome but do not share the good prognosis. We conclude that the 5q-syndrome may be best defined as primary MDS of the FAB type RA with a 5q deletion as the sole karyotypic abnormality. This simple definition will distinguish patients with a good prognosis and all the classical features of the 5q-syndrome.


Mitochondrial morphology differences and mitophagy deficit in murine glaucomatous optic nerve.
Decreased ATP correlates with intraocular pressure exposure in the optic nerves of mice with glaucoma. To understand what underlies this energy deficit, we examined mitochondria in the myelinated optic nerve axons of the DBA/2J mouse, a model of glaucoma secondary to iris pigment disease, and the DBA/2(wt-gpnmb) control strain. Mitochondrial length, width, surface area, and health status were measured in 30 electron microscopic fields within the myelinated portion of optic nerves from DBA/2J and DBA/2(wt-gpnmb) mice at 3, 6, and 10 months of age. Protein was isolated from optic nerve for analysis of PINK1, Parkin, LC3-I and -II, and lysosome-associated membrane protein 1 (LAMP1) by Western blot. The number of mitochondria in DBA/2J optic nerve was increased, and they had significantly smaller surface area. Mitochondria in DBA/2J were closer to the axolemma, more spatially isolated, and their cristae were more disrupted at every age group as compared to DBA/2(wt-gpnmb). Autophagosomes were significantly increased in DBA/2J optic nerve at all ages. Protein analysis showed higher LC3-II to LC3-I ratio in aged DBA/2J optic nerve than in DBA/2(wt-gpnmb). PINK1 and Parkin levels were not statistically different across age groups. LAMP1 was significantly decreased in the aged DBA/2J optic nerve. Decreased surface area, combined with reduced oxidative capacity in mitochondria from the aged DBA/2J axon, indicate that mitochondrial pathology may contribute to the energy deficit in glaucomatous optic nerve. Though autophagosomes were increased in DBA/2J optic nerve, the increased mitochondria and decreased LAMP1 suggest deteriorating mitochondria are not being efficiently recycled by mitophagy.


Genome-derived insights into the biology of the hepatotoxic bloom-forming cyanobacterium Anabaena sp. strain 90.
Cyanobacteria can form massive toxic blooms in fresh and brackish bodies of water and are frequently responsible for the poisoning of animals and pose a health risk for humans. Anabaena is a genus of filamentous diazotrophic cyanobacteria commonly implicated as a toxin producer in blooms in aquatic ecosystems throughout the world. The biology of bloom-forming cyanobacteria is poorly understood at the genome level. Here, we report the complete sequence and comprehensive annotation of the bloom-forming Anabaena sp. strain 90 genome. It comprises two circular chromosomes and three plasmids with a total size of 5.3 Mb, encoding a total of 4,738 genes. The genome is replete with mobile genetic elements. Detailed manual annotation demonstrated that almost 5% of the gene repertoire consists of pseudogenes. A further 5% of the genome is dedicated to the synthesis of small peptides that are the products of both ribosomal and nonribosomal biosynthetic pathways. Inactivation of the hassallidin (an antifungal cyclic peptide) biosynthetic gene cluster through a deletion event and a natural mutation of the buoyancy-permitting gvpG gas vesicle gene were documented. The genome contains a large number of genes encoding restriction-modification systems. Two novel excision elements were found in the nifH gene that is required for nitrogen fixation. Genome analysis demonstrated that this strain invests heavily in the production of bioactive compounds and restriction-modification systems. This well-annotated genome provides a platform for future studies on the ecology and biology of these important bloom-forming cyanobacteria.


The mechanism of hydrogen adsorption on transition metal dichalcogenides as hydrogen evolution reaction catalyst.
Two-dimensional transition metal dichalcogenides (TMDs) have been widely considered as potential hydrogen evolution reaction (HER) catalysts because of their low cost and good electrochemical stability in acid conditions. The mechanism of hydrogen adsorption on TMDs plays an important role in optimizing HER activity. In this research, a series of TMDs (MX2, M = Co, Cr, Fe, Mn, Mo, Nb, Ni, Re, Sc, Tc, Ti, V, W, Zr, and X = S, Se, Te) in 2H- and 1T-phases were investigated using density functional theory to determine the relationship between hydrogen adsorption free energy (ΔGH) and electronic structure using a simple descriptor. The results showed a positive linear relation between ΔGH and the work required of the H electron to fill the unoccupied electronic states of the TMDs. Based on such linear relationships, the various defects (B-, C-, N-, O-, F-, P-, Se-doping and S-vacancy) were used to activate the inert basal planes of the 2H-phase molybdenum disulfide, which can introduce impurity states in the lower energy level to effectively accommodate the H electron. Furthermore, HER activity can be further optimized with the increasing concentration of the defects. These findings provide a practicable map of the HER performances, as well as indicating an appropriate direction for optimizing HER activity.


Directed Molecular Stacking for Engineered Fluorescent Three-Dimensional Reduced Graphene Oxide and Coronene Frameworks.
Three-dimensional fluorescent graphene frameworks with controlled porous morphologies are of significant importance for practical applications reliant on controlled structural and electronic properties, such as organic electronics and photochemistry. Here we report a synthetically accessible approach concerning directed aromatic stacking interactions to give rise to new fluorogenic 3D frameworks with tuneable porosities achieved through molecular variations. The binding interactions between the graphene-like domains present in the in situ-formed reduced graphene oxide (rGO) with functional porphyrin molecules lead to new hybrids via an unprecedented solvothermal reaction. Functional free-base porphyrins featuring perfluorinated aryl groups or hexyl chains at their meso- and β-positions were employed in turn to act as directing entities for the assembly of new graphene-based and foam-like frameworks and of their corresponding coronene-based hybrids. Investigations in the dispersed phase and in thin-film by XPS, SEM and FLIM shed light onto the nature of the aromatic stacking within functional rGO frameworks (denoted rGOFs) which was then modelled semi-empirically and by DFT calculations. The pore sizes of the new emerging reduced graphene oxide hybrids are tuneable at the molecular level and mediated by the bonding forces with the functional porphyrins acting as the "molecular glue". Single crystal X-ray crystallography described the stacking of a perfluorinated porphyrin with coronene, which can be employed as a molecular model for understanding the local aromatic stacking order and charge transfer interactions within these rGOFs for the first time. This opens up a new route to controllable 3D framework morphologies and pore size from the Ångstrom to the micrometre scale. Theoretical modelling showed that the porosity of these materials is mainly due to the controlled inter-planar distance between the rGO, coronene or graphene sheets. The host-guest chemistry involves the porphyrins acting as guests held through π-π stacking, as demonstrated by XPS. The objective of this study is also to shed light into the fundamental localised electronic and energy transfer properties in these new molecularly engineered porous and fluorogenic architectures, aiming in turn to understand how functional porphyrins may exert stacking control over the notoriously disordered local structure present in porous reduced graphene oxide fragments. By tuning the porosity and the distance between the graphene sheets using aromatic stacking with porphyrins, it is also possible to tune the electronic structure of the final nanohybrid material, as indicated by FLIM experiments on thin films. Such nanohybrids with highly controlled pores dimensions and morphologies open the way to new design and assembly of storage devices and applications incorporating π-conjugated molecules and materials and their π-stacks may be relevant towards selective separation membranes, water purification and biosensing applications.


Depression, self-focused attention, and expectancies for positive and negative future life events for self and others.
In two studies, we examined depressed and nondepressed persons' judgments of the probability of future positive and negative life events occurring to themselves and to others. Study 1 demonstrated that depressed subjects were generally less optimistic than their nondepressed counterparts: Although nondepressed subjects rated positive events as more likely to happen to themselves than negative events, depressed subjects did not. In addition, relative to nondepressed subjects, depressed subjects rated positive events as less likely to occur to themselves and more likely to occur to others and negative events as more likely to occur to both self and others. Study 2 investigated the role that differential levels of self-focused attention might play in mediating these differences. On the basis of prior findings that depressed persons generally engage in higher levels of self-focus than nondepressed persons do and the notion that self-focus activates one's self-schema, we hypothesized that inducing depressed subjects to focus externally would attenuate their pessimistic tendencies. Data from Study 2 supported the hypothesis that high levels of self-focus partially mediate depressive pessimism: Whereas self-focused depressed subjects were more pessimistic than nondepressed subjects, externally focused depressed subjects were not. The role of attentional focus in maintaining these and other depressive pessimistic tendencies was discussed.


[Auditory-perceptive, acoustic and vocal self-perception analyses in children].
To establish the occurrence of dysphonic children and to relate data from auditory-perceptive, acoustic and vocal self-perception analyses of dysphonic and non-dysphonic children. Participants were 70 children, 37 female and 33 male, with ages ranging from 6 to 10 years. The sustained emission of the vowel /a/ was recorded, and children replied to the question "What do you think of your voice?".After that, the auditory-perceptive analysis of their voices was carried out, based on the parameters of the GRBASI scale. The acoustic analysis was also conducted, considering the following measures: fundamental frequency, frequency and amplitude perturbation quotient, and harmonic-to-noise ratio. The self-perception analysis of the subjects' voices was based on content analysis. Data were statistically analyzed. The occurrence of dysphonic children was 37.14%. Breathiness was the most common vocal quality among dysphonic children, followed by roughness, which was also common. The acoustic measures frequency and amplitude perturbation quotient and harmonic-to-noise ration were higher among dysphonic children. However, these measures were similar between children that had positive self-perception and those with negative self-perception. Negative self-perception was more frequent among dysphonic children. The occurrence of dysphonia in the studied group was 37.14%. Dysphonic children present negative self-perception of their voices, voice quality predominantly rough and/or breathy, and altered acoustic measures, when compared to non-dysphonic children.


Comparison of Outcomes between Direct-to-Implant Breast Reconstruction Following Nipple-Sparing Mastectomy through Inframammary Fold Incision versus Noninframammary Fold Incision.
In properly selected patients with breast cancer, nipple-sparing mastectomy (NSM) is generally considered safe by oncologic standards. We examined two groups of patients who underwent direct-to-implant (DTI) reconstruction after NSM, comparing complications encountered, revision rates, and aesthetic outcomes. The patients were stratified based on type of surgical incision and assigned to inframammary fold (IMF) and non-IMF groups. We investigated 141 patients (145 breasts) subjected to NSM and immediate DTI reconstruction between 2013 and 2016. A total of 62 breasts (in 58 patients) were surgically removed via IMF incisions, with the other 83 breasts (in 83 patients) removed by non-IMF means. Complications associated with IMF (n=62) and non-IMF (n=83) incisions were as follows: skin necrosis (IMF, 9; non-IMF, 18); hematoma (IMF, 3; non-IMF, 4); seroma (IMF, 8; non-IMF, 4); mild capsular contracture (IMF, 4; non-IMF, 7); and tumor recurrence (IMF, 2; non-IMF, 8). Surgical revisions were counted as duplicates (IMF, 18; non-IMF, 38). Aesthetic outcomes following IMF incisions were rated as very good (44.2%), good (23.1%), fair (23.1%), or poor (9.6%). IMF incision enables complete preservation of the nipple-areolar complex, yielding superior aesthetic results in immediate DTI breast reconstruction after NSM. The nature of incision used had no significant impact on postoperative complications or reoperation rates and had comparable oncologic safety to that of non-IMF incisions. IMF incisions produced the least visible scarring and did not affect breast shape. Most patients were satisfied with the aesthetic outcomes.


Assessing improvement in disease prediction using net reclassification improvement: impact of risk cut-offs and number of risk categories.
Net reclassification improvement (NRI) has received much attention for comparing risk prediction models, and might be preferable over the area under the receiver operating characteristics (ROC) curve to indicate changes in predictive ability. We investigated the influence of the choice of risk cut-offs and number of risk categories on the NRI. Using data of the European Prospective Investigation into Cancer and Nutrition-Potsdam study, three diabetes prediction models were compared according to ROC area and NRI with varying cut-offs for two and three risk categories and varying numbers of risk categories. When compared with a basic model, including age, anthropometry, and hypertension status, a model extension by waist circumference improved discrimination from 0.720 to 0.831 (0.111 [0.097-0.125]) while increase in ROC-AUC from 0.831 to 0.836 (0.006 [0.002-0.009]) indicated moderate improvement when additionally considering diet and physical activity. However, NRI based on these two model comparisons varied with varying cut-offs for two (range: 5.59-23.20%; -0.79 to 4.09%) and three risk categories (20.37-40.15%; 1.22-4.34%). This variation was more pronounced in the model extension showing a larger difference in ROC-AUC. NRI increased with increasing numbers of categories from minimum NRIs of 18.41 and 0.46% to approximately category-free NRIs of 79.61 and 19.22%, but not monotonically. There was a similar pattern for this increase in both model comparisons. In conclusion, the choice of risk cut-offs and number of categories has a substantial impact on NRI. A limited number of categories should only be used if categories have strong clinical importance.


QiHong prevents death in coxsackievirus B3 induced murine myocarditis through inhibition of virus attachment and penetration.
Viral myocarditis affects about 5% to 20% of the population. So far, there are not many effective antiviral treatments available. QiHong, the combination of the extracts from Astragali (Huangqi), Rhadiola rosea (Hongjingtian), and Sophora flavescens (Kushen), was developed based on laboratory research. The aim of this study was to investigate the effect and mechanism of QiHong on coxsackievirus B3 (CVB3)-induced myocarditis. The antiviral activity of QiHong in vitro was evaluated on HeLa and Vero cells infected by CVB3. Ribavirin was chosen as positive control. Our results showed that QiHong possessed potent antiviral effects on CVB3 by sodium 3'-[1-(phenylamino-carbonyl)-3, 4-tetrazolium]-bis (4-methoxy-6-nitro) benzene sulfonic acid and plaque-forming assay (50% inhibitory concentrations [IC50] were 7.16 +/- 0.8 microg/ml and 2.63 +/- 0.5 microg/ml, respectively). The 50% cytotoxicity concentration (CC50) was 16-fold higher in QiHong-treated cells than in ribavirin-treated cells. Time course studies demonstrated that the antiviral effect of QiHong was mainly found during 0-4 hrs of infection, and it blocked the attachment and penetration of CVB3 into cells. In vivo 4-week-old male Balb/C mice were used and inoculated intraperitoneally with CVB3 suspension or normal saline. At 48 hrs after inoculation, the infected mice were gavaged with QiHong or ribavirin. On Day 6, myocardial virus titers were significantly lower in the QiHong-treated group than in the viral-infected groups. On Day 14, QiHong significantly ameliorated CVB3-induced myocardium necrosis; on Day 28, QiHong treatment increased survival rate 4-fold compared with CVB3-infected controls (64% vs. 16%; P < 0.05). The results showed that QiHong is a very promising potent antiviral agent with a highly significant favorable effect on survival and pathologic changes in CVB3-induced myocarditis with less toxicity than ribavirin. The antiviral activity of QiHong is at least partially due to an inhibitory effect on virus attachment and penetration.


Cow's milk proteins cause infantile colic in breast-fed infants: a double-blind crossover study.
Sixty-six mothers of 66 breast-fed infants with infantile colic were put on a diet free from cow's milk. The colic disappeared in 35 infants; it reappeared on at least two challenges (cow's milk to mother) in 23 infants (35%). A double-blind crossover trial with cow's milk whey protein was performed in 16 of these 23 mothers and infants. Six infants had to be taken out of the study for various reasons; of the remaining ten infants, nine reacted with colic after their mothers' intake of whey protein-containing capsules. Sequential analysis showed a high correlation between infantile colic in breast-fed infants and their mothers' consumption of cow's milk protein. A diet free of cow's milk is suggested for the mothers as a first trial of treatment of infantile colic in breast-fed infants.


Optimal Selection of Radiotherapy as Part of a Multimodal Approach for Hepatocellular Carcinoma.
A multimodal approach to treatment is a basic oncologic principle with proven survival benefits for most cancer types. However, existing guidelines recommend single modalities for treating each stage of hepatocellular carcinoma (HCC). Nonetheless, multimodal approaches can be considered for HCC, depending on the characteristics of the disease in individual cases. Radiotherapy (RT), an effective local modality, is a critical element of most multimodal approaches. Improved RTtechnology and increased understanding of the tolerance of the liver to radiation have contributed to the popularity of RT for treating liver tumors in clinical practice. Consequently, numerous reports have described the effects of RT on liver cancer, despite a lack of stringent evidence for its benefits. RT can be delivered using various technologies and approaches, which may be the source of some confusion. For example, high-dose ablative RT can be curative on its own, or high-dose ablative or conventional RT can complement other treatments such as radiofrequency ablation and transarterial chemoembolization. Combinations of systemic agents and RT can also be applied. This review discusses the optimal selection of RT as part of a multimodal approach for HCC.


Subcritical Water Technology for Enhanced Extraction of Biochemical Compounds from Chlorella vulgaris.
Subcritical water extraction (SWE) technology has been used for the extraction of active compounds from different biomass materials with low process cost, mild operating conditions, short process times, and environmental sustainability. With the limited application of the technology to microalgal biomass, this work investigates parametrically the potential of subcritical water for high-yield extraction of biochemicals such as carbohydrates and proteins from microalgal biomass. The SWE process was optimized using central composite design (CCD) under varying process conditions of temperature (180-374°C), extraction time (1-20 min), biomass particulate size (38-250 μm), and microalgal biomass loading (5-40 wt.%). Chlorella vulgaris used in this study shows high volatile matter (83.5 wt.%) and carbon content (47.11 wt.%), giving advantage as a feedstock for biofuel production. The results showed maximum total carbohydrate content and protein yields of 14.2 g/100 g and 31.2 g/100 g, respectively, achieved under the process conditions of 277°C, 5% of microalgal biomass loading, and 5 min extraction time. Statistical analysis revealed that, of all the parameters investigated, temperature is the most critical during SWE of microalgal biomass for protein and carbohydrate production.


Context is key: Parasympathetic regulation in the classroom differentially predicts preschoolers' socially competent behaviors.
Research shows that children's early social competence predicts their later academic and interpersonal success. Accordingly, early childhood education programs increasingly aim to evaluate and support children's social skill development. Despite ample theoretical and empirical work demonstrating the role of the parasympathetic nervous system (PNS) in supporting neurophysiological processes that underlie social behaviors, no study has explicitly tested whether the assessment of PNS activity in childhood educational settings provides insight into children's social functioning. The current study addresses this gap by examining the influence of context-specific PNS regulation, assessed via respiratory sinus arrhythmia (RSA), in predicting preschool children's socially competent behavior toward peers in the classroom. Results showed that: (1) RSA withdrawal (e.g., decreases relative to a baseline task) during unstructured classroom activities predicted children's socially competent behaviors during these unstructured activities but not during structured activities, whereas (2) withdrawal during structured classroom activities predicted children's socially competent behaviors during structured activities. These results indicate that PNS activity makes context-specific contributions to children's social behaviors and highlight the importance of assessing neurophysiological regulation in context.