Strategies for defining financial benchmarks for the research mission in academic health centers.
Valid financial benchmarks are needed for the research mission in academic health centers (AHCs). Databases listing institutional success in obtaining sponsored research funding are publicly available. However, these databases are generally not adjusted for AHC size, confounding useful comparisons between institutions. The authors suggest simple strategies, which depend on a form of ratio analysis, to circumvent this limitation. Annual rates of growth (rates of return, R(f)) are determined for total National Institutes of Health research grant dollars, number of research grants, and average dollars per research grant for 15 U.S. AHCs. Selected institutions are compared to one another and to the total pool of medical school funding. Performance is evaluated over a ten-year period (1992-2001) to illustrate the advantages, limitations, and applications of the ratio analysis approach. Alternative strategies are suggested for individual AHCs to evaluate their departmental and organizational performance, again without regard to institution size, and also dependent on ratios. Application of these strategies, especially when individualized to the particular AHC, permits more accurate assessment of past performance and more accurate and effective planning for future growth.


Grain-size considerations for optoelectronic multistage interconnection networks.
This paper investigates, at the system level, the performance-cost trade-off between optical and electronic interconnects in an optoelectronic interconnection network. The specific system considered is a packet-switched, free-space optoelectronic shuffle-exchange multistage interconnection network (MIN). System bandwidth is used as the performance measure, while system area, system power, and system volume constitute the cost measures. A detailed design and analysis of a two-dimensional (2-D) optoelectronic shuffle-exchange routing network with variable grain size K is presented. The architecture permits the conventional 2 x 2 switches or grains to be generalized to larger K x K grain sizes by replacing optical interconnects with electronic wires without affecting the functionality of the system. Thus the system consists of log(k) N optoelectronic stages interconnected with free-space K-shuffles. When K = N, the MIN consists of a single electronic stage with optical input-output. The system design use an effi ient 2-D VLSI layout and a single diffractive optical element between stages to provide the 2-D K-shuffle interconnection. Results indicate that there is an optimum range of grain sizes that provides the best performance per cost. For the specific VLSI/GaAs multiple quantum well technology and system architecture considered, grain sizes larger than 256 x 256 result in a reduced performance, while grain sizes smaller than 16 x 16 have a high cost. For a network with 4096 channels, the useful range of grain sizes corresponds to approximately 250-400 electronic transistors per optical input-output channel. The effect of varying certain technology parameters such as the number of hologram phase levels, the modulator driving voltage, the minimum detectable power, and VLSI minimum feature size on the optimum grain-size system is studied. For instance, results show that using four phase levels for the interconnection hologram is a good compromise for the cost functions mentioned above. As VLSI minimum feature sizes decrease, the optimum grain size increases, whereas, if optical interconnect performance in terms of the detector power or modulator driving voltage requirements improves, the optimum grain size may be reduced. Finally, several architectural modifications to the system, such as K x K contention-free switches and sorting networks, are investigated and optimized for grain size. Results indicate that system bandwidth can be increased, but at the price of reduced performance/cost. The optoelectronic MIN architectures considered thus provide a broad range of performance/cost alternatives and offer a superior performance over purely electronic MIN's.


Methodologies for pre-validation of biofilters and wetlands for stormwater treatment.
Water Sensitive Urban Design (WSUD) systems are frequently used as part of a stormwater harvesting treatment trains (e.g. biofilters (bio-retentions and rain-gardens) and wetlands). However, validation frameworks for such systems do not exist, limiting their adoption for end-uses such as drinking water. The first stage in the validation framework is pre-validation, which prepares information for further validation monitoring. A pre-validation roadmap, consisting of five steps, is suggested in this paper. Detailed methods for investigating target micropollutants in stormwater, and determining challenge conditions for biofilters and wetlands, are provided. A literature review was undertaken to identify and quantify micropollutants in stormwater. MUSIC V5.1 was utilized to simulate the behaviour of the systems based on 30-year rainfall data in three distinct climate zones; outputs were evaluated to identify the threshold of operational variables, including length of dry periods (LDPs) and volume of water treated per event. The paper highlights that a number of micropollutants were found in stormwater at levels above various worldwide drinking water guidelines (eight pesticides, benzene, benzo(a)pyrene, pentachlorophenol, di-(2-ethylhexyl)-phthalate and a total of polychlorinated biphenyls). The 95th percentile LDPs was exponentially related to system design area while the 5th percentile length of dry periods remained within short durations (i.e. 2-8 hours). 95th percentile volume of water treated per event was exponentially related to system design area as a percentage of an impervious catchment area. The out-comings of this study show that pre-validation could be completed through a roadmap consisting of a series of steps; this will help in the validation of stormwater treatment systems.


Albuminuria after renal transplantation: maintenance with sirolimus/low-dose tacrolimus vs. mycophenolate mofetil/high-dose tacrolimus.
Maintenance immunosuppression with sirolimus (SRL) in renal transplantation has been associated with proteinuria. We report long-term outcomes of kidney transplant recipients maintained on steroid-free regimens, either SRL with low-dose tacrolimus (SRL/L-Tac) or mycophenolate mofetil (MMF) with high-dose tacrolimus (MMF/H-Tac). We conducted a case-matched study of 50 patients receiving MMF/H-Tac, matched 1:2 with 100 patients maintained on SRL/L-Tac. All patients were induced with rabbit antithymocyte globulin followed by early steroid withdrawal. Comparisons were made of patient and graft survival, graft function, acute rejection, and albuminuria. There were no significant differences between the SRL/L-Tac and MMF/H-Tac groups for patient survival, graft survival, occurrence of acute rejection, or graft function. There was no difference in the proportion of patients with albumin/creatinine ratio (ACR) ≥300 μg/mg (19% vs. 20%), but more patients in the SRL group were receiving renin-angiotensin system blocking agents (72% vs. 53%, p = 0.04). Only flushing the donor kidney with histidine-tryptophan-ketoglutarate solution (vs. UW solution) was predictive of albuminuria. Long-term outcomes are similar at our center for kidney transplant patients receiving either SRL/L-Tac or MMF/H-Tac. Although the occurrence of albuminuria was not different, significantly more SRL-treated patients were receiving antiproteinuric medications.


Potential of diagnostic microbiology for treatment and prognosis of dental caries and periodontal diseases.
Most evidence suggests that only a finite number of bacteria are responsible for dental caries and periodontal diseases. This knowledge led to the development of microbial tests which can identify suspected pathogens. Current evaluation of the diagnostic power of microbial tests has shown that they have a low sensitivity and a low prognostic value. Despite these shortcomings, there are valid indications for microbiological-based diagnosis. Salivary microbial tests for the detection of mutans streptococci and lactobacilli may be useful, for example, in young children, oligosialic patients, and orthodontic patients. These tests can be used to monitor the success of chemopreventive measures or compliance with dietary recommendations. Microbial diagnosis, may also be valuable in the treatment of early-onset periodontitis or in subjects who respond poorly to periodontal therapy. The use of microbial tests to monitor the efficacy of chemotherapy or mechanical treatment is of particular interest.


Differential recruitment of activating and inhibitory Fc gamma RII during phagocytosis.
Human myeloid cells express both activating and inhibitory receptors of the FcgammaRII family. FcgammaRIIA mediates processes associated with cell activation, including phagocytosis of IgG-opsonized particles, whereas coengagement of the inhibitory FcgammaRIIB downregulates such signaling. We analyzed the relative recruitment of these two receptors during phagocytosis of IgG-coated particles by ts20 Chinese hamster fibroblast cells cotransfected with both receptors carrying distinguishable fluorescent protein tags. We found that FcgammaRIIA is substantially enriched at sites of particle binding relative to its inhibitory counterpart, with a greater than 2-fold increase in the local ratio of activating to inhibitory receptor compared with that for the plasma membrane as a whole. Experiments with chimeric receptors revealed that the preferential enrichment of FcgammaRIIA results from differences between the extracellular domains of the receptors, and indicated that the lesser recruitment of FcgammaRIIB limits its ability to effectively inhibit FcgammaRIIA-mediated phagocytosis. Mutagenesis studies indicated that FcgammaRIIA residues leucine 132 and phenylalanine 160, which lie in IgG-binding regions of FcgammaRIIA and which differ in FcgammaRIIB, both contribute to the local relative enrichment of FcgammaRIIA by increasing its affinity for IgG1 relative to that of FcgammaRIIB. In human monocytes, engagement of approximately equal amounts of FcgammaRIIB was required to substantially inhibit FcgammaRIIA-mediated phagocytosis. These results demonstrate that differences in affinity for IgG between activating and inhibitory FcgammaR can result in substantial local changes in their relative concentrations during phagocytosis, with important functional consequences.


[The role of tadalafil in the management of sexual dysfunctions].
Erectile dysfunction (ED) has a significant negative impact on the quality of life of the patients and their partners. The sequence and regimens of ED therapy have become quite evident since the advent of phosphodiesterase type 5 inhibitors (PDE-5). However, there have been continued basic research of the efficacy and safety of these agents and studies aimed at new therapeutic goals. In recent years, the attention of researchers has shifted into a wider range of issues related to the personalized PDE-5 therapy, including sexual satisfaction, psychosocial variables (e.g., confidence, self-esteem, quality of relationships) and other potentially related factors. In particular, there are more and more new data on male sexual dysfunction. This review focuses on the relationship between erectile dysfunction and concomitant conditions: depressive symptoms, libido and sexual satisfaction disorders, ejaculation and orgasm abnormalities. The authors outline the possibilities and potential benefits of PDE-5 for patients with comorbid sexual dysfunction and depression with a special focus on tadalafil.


High survivorship after catch-and-release fishing suggests physiological resilience in the endothermic shortfin mako shark (Isurus oxyrinchus).
The shortfin mako shark (Isurus oxyrinchus) is a species commonly targeted by commercial and recreational anglers in many parts of the developed world. In Australia, the species is targeted by recreational anglers only, under the assumption that most of the sharks are released and populations remain minimally impacted. If released sharks do not survive, the current management strategy will need to be revised. Shortfin mako sharks are commonly subjected to lengthy angling events; however, their endothermic physiology may provide an advantage over ectothermic fishes when recovering from exercise. This study assessed the post-release survival of recreationally caught shortfin mako sharks using Survivorship Pop-up Archival Transmitting (sPAT) tags and examined physiological indicators of capture stress from blood samples as well as any injuries that may be caused by hook selection. Survival estimates were based on 30 shortfin mako sharks captured off the south-eastern coast of Australia. Three mortalities were observed over the duration of the study, yielding an overall survival rate of 90%. All mortalities occurred in sharks angled for <30 min. Sharks experienced increasing plasma lactate with longer fight times and higher sea surface temperatures (SSTs), increased plasma glucose at higher SSTs and depressed expression of heat shock protein 70 and β-hydroxybutyrate at higher SSTs. Long fight times did not impact survival. Circle hooks significantly reduced foul hooking when compared with J hooks. Under the conditions of this study, we found that physical injury associated with hook choice is likely to have contributed to an increased likelihood of mortality, whereas the high aerobic scope associated with the species' endothermy probably enabled it to cope with long fight times and the associated physiological responses to capture.


Could we have known? A qualitative analysis of data from women who survived an attempted homicide by an intimate partner.
To examine in-depth the lives of women whose partners attempted to kill them, and to identify patterns that may aid in the clinician's ability to predict, prevent, or counsel about femicide or attempted femicide. Qualitative analysis of 30 in-depth interviews. Six U.S. cities. Thirty women, aged 17-54 years, who survived an attempted homicide by an intimate partner. All but 2 of the participants had previously experienced physical violence, controlling behavior, or both from the partner who attempted to kill them. The intensity of the violence, control, and threats varied greatly, as did the number of risk factors measured by the Danger Assessment, defining a wide spectrum of prior abuse. Approximately half (14/30) of the participants did not recognize that their lives were in danger. Women often focused more on relationship problems involving money, alcohol, drugs, possessiveness, or infidelity, than on the risk to themselves from the violence. The majority of the attempts (22/30) happened around the time of a relationship change, but the relationship was often ending because of problems other than violence. Clinicians should not be falsely reassured by a woman's sense of safety, by the lack of a history of severe violence, or by the presence of few classic risk factors for homicide. Efforts to reduce femicide risk that are targeted only at those women seeking help for violence-related problems may miss potential victims.


A piece in the puzzle of intrauterine fetal death: pathological findings in placentas from term and preterm intrauterine fetal death pregnancies.
To compare pathological findings of placentas from term and preterm pregnancies complicated by intrauterine fetal death (IUFD). A retrospective cohort study was conducted including deliveries complicated by IUFD. A comparison was made between placentas from term and preterm (<37 weeks' gestation) pregnancies complicated by IUFD. A second analysis was undertaken comparing IUFD placentas delivered before and after 34 weeks' gestation. Uteroplacental insufficiency was defined when one or more of the following pathological features were found: placental infarct, poor vascularity of the chorionic villi, intravascular thrombi and vascular occlusion. During the study period, 849 placentas of IUFD were examined. Gross and microscopic pathological finding were noted. When comparing gross and microscopic findings in term and preterm (<37 weeks) IUFD placentas, higher rates of calcifications, tissue congestion and cellular metaplasia were found in term vs. preterm placentas. Significantly increased rates of poor tissue vascularity, placental vascular occlusion and uteroplacental insufficiency were demonstrated in preterm IUFD placentas. When comparing pathological findings in IUFD placentas delivered before and after 34 weeks' gestation, higher rates of abnormal cord insertion, calcifications, tissue congestion, infarcts and intravascular thrombi as well as poor tissue vascularity and placental vascular occlusion were demonstrated in IUFD placentas delivered before 34 weeks. Regardless of gestational age at the time of IUFD in more than 90% of placentas vascular wall thickening was found. A third of both term and preterm placentas demonstrated histological chorioamionitis. A vast majority of IUFD placentas reveal numerous pathological findings that reflect uteroplacental insufficiency and abnormal blood supply. Different characteristics were noted in term and preterm placentas of pregnancies complicated by IUFD. Better definition of causes and associated placental pathological findings of IUFD might aid clinicians in counseling such patients regarding the reason and risk of recurrence in subsequent pregnancies.


Comparative genomics of a subset of Adherent/Invasive Escherichia coli strains isolated from individuals without inflammatory bowel disease.
There is increased evidence demonstrating the association between Crohn's Disease (CD), a type of Inflammatory Bowel Disease (IBD), and non-diarrheagenic Adherent/Invasive Escherichia coli (AIEC) isolates. AIEC strains are phenotypically characterized by their adhesion, invasion and intra-macrophage survival capabilities. In the present study, the genomes of five AIEC strains isolated from individuals without IBD (four from healthy donors and one from peritoneal liquid) were sequenced and compared with AIEC prototype strains (LF82 and NRG857c), and with extra-intestinal uropathogenic strain (UPEC CFT073). Non-IBD-AIEC strains showed an Average Nucleotide Identity up to 98% compared with control strains. Blast identities of the five non-IBD-AIEC strains were higher when compared to AIEC and UPEC reference strains than with another E. coli pathotypes, suggesting a relationship between them. The SNPs phylogeny grouped the five non-IBD-AIEC strains in one separated cluster, which indicates the emergence of these strains apart from the AIEC group. Additionally, four genomic islands not previously reported in AIEC strains were identified. An incomplete Type VI secretion system was found in non-IBD-AIEC strains; however, the Type II secretion system was complete. Several groups of genes reported in AIEC strains were searched in the five non-IBD-AIEC strains, and the presence of fimA, fliC, fuhD, chuA, irp2 and cvaC were confirmed. Other virulence factors were detected in non-IBD-AIEC strains, which were absent in AIEC reference strains, including EhaG, non-fimbrial adhesin 1, PapG, F17D-G, YehA/D, FeuC, IucD, CbtA, VgrG-1, Cnf1 and HlyE. Based on the differences in virulence determinants and SNPs, it is plausible to suggest that non-IBD AIEC strains belong to a different pathotype.


Dabigatran etexilate for stroke prevention in patients with atrial fibrillation: resolving uncertainties in routine practice.
Dabigatran etexilate is a new oral anticoagulant recently approved in Europe for the prevention of stroke or systemic embolism in adult patients with non-valvular atrial fibrillation (AF) and at least one risk factor for stroke. With a fast onset of action and a predictable anticoagulant effect obviating the need for coagulation monitoring, dabigatran etexilate offers practical advantages over vitamin K antagonists in clinical practice. However, clinicians may have questions about practical aspects of dabigatran etexilate use including monitoring anticoagulant efficacy, interruption for surgical or invasive procedures and management of bleeding. This review article aims to address these concerns and provide guidance on the use of dabigatran etexilate in special situations, such as acute coronary syndromes and cardiac revascularisation. In addition, cut-off values for different coagulation assay results associated with an increased risk of bleeding are given.


Quantum statistics of broadband squeezed light.
Photon-emission sequences in nonclassical light beams generated by an optical parametric oscillator are studied. Exact photon-counting and waiting time distributions are derived by using a generating function technique based on the positive-P representation. This approach is used to present a simple physical picture of photon emissions from this nonclassical light source.


New beaked whales from the late Miocene of Peru and evidence for convergent evolution in stem and crown Ziphiidae (Cetacea, Odontoceti).
The Ziphiidae (beaked whales) represent a large group of open-ocean odontocetes (toothed cetaceans), whose elusive and deep diving behavior prevents direct observation in their natural habitat. Despite their generally large body size, broad geographical distribution, and high species number, ziphiids thus remain poorly known. Furthermore, the evolutionary processes that have led to their extreme adaptations and impressive extant diversity are still poorly understood. Here we report new fossil beaked whales from the late Miocene of the Pisco Formation (southern Peru). The best preserved remains here described are referred to two new genera and species, the Messinian Chavinziphius maxillocristatus and the Tortonian Chimuziphius coloradensis, based on skull remains from two marine vertebrate-rich localities: Cerro Los Quesos and Cerro Colorado, respectively. C. maxillocristatus is medium sized retains a complete set of functional lower teeth, and bears robust rostral maxillary crests similar to those of the extant Berardius. By contrast, C. coloradensis is small and characterized by large triangular nasals and moderately thickened premaxillae that dorsally close the mesorostral groove. Both species confirm the high past diversity of Ziphiidae, the richest cetacean family in terms of the number of genera and species. Our new phylogenetic and biogeographical analyses depart markedly from earlier studies in dividing beaked whales into two major clades: the Messapicetus clade, which, along with other stem ziphiids, once dominated the southeastern Pacific and North Atlantic; and crown Ziphiidae, the majority of which are found in deep-water regions of the Southern Ocean, with possible subsequent dispersal both globally (Mesoplodon and Ziphius) and to the cooler waters of the northern oceans (Berardius and Hyperoodon). Despite this relatively clear separation, both lineages seem to follow similar evolutionary trends, including (1) a progressive reduction of dentition; (2) an increase in the compactness and thickness of the rostral bones; (3) similar changes in facial morphology (e.g., elevation of the vertex); and (4) an increase of body size. We suggest that these trends may be linked to a convergent ecological shift to deep diving and suction feeding.


A short note on dynamic programming in a band.
Third generation sequencing technologies generate long reads that exhibit high error rates, in particular for insertions and deletions which are usually the most difficult errors to cope with. The only exact algorithm capable of aligning sequences with insertions and deletions is a dynamic programming algorithm. In this note, for the sake of efficiency, we consider dynamic programming in a band. We show how to choose the band width in function of the long reads' error rates, thus obtaining an [Formula: see text] algorithm in space and time. We also propose a procedure to decide whether this algorithm, when applied to semi-global alignments, provides the optimal score. We suggest that dynamic programming in a band is well suited to the problem of aligning long reads between themselves and can be used as a core component of methods for obtaining a consensus sequence from the long reads alone. The function implementing the dynamic programming algorithm in a band is available, as a standalone program, at: https://forgemia.inra.fr/jean-francois.gibrat/BAND_DYN_PROG.git.


Feature driven classification of Raman spectra for real-time spectral brain tumour diagnosis using sound.
Spectroscopic diagnostics have been shown to be an effective tool for the analysis and discrimination of disease states from human tissue. Furthermore, Raman spectroscopic probes are of particular interest as they allow for in vivo spectroscopic diagnostics, for tasks such as the identification of tumour margins during surgery. In this study, we investigate a feature-driven approach to the classification of metastatic brain cancer, glioblastoma (GB) and non-cancer from tissue samples, and we provide a real-time feedback method for endoscopic diagnostics using sound. To do this, we first evaluate the sensitivity and specificity of three classifiers (SVM, KNN and LDA), when trained with both sub-band spectral features and principal components taken directly from Raman spectra. We demonstrate that the feature extraction approach provides an increase in classification accuracy of 26.25% for SVM and 25% for KNN. We then discuss the molecular assignment of the most salient sub-bands in the dataset. The most salient sub-band features are mapped to parameters of a frequency modulation (FM) synthesizer in order to generate audio clips from each tissue sample. Based on the properties of the sub-band features, the synthesizer was able to maintain similar sound timbres within the disease classes and provide different timbres between disease classes. This was reinforced via listening tests, in which participants were able to discriminate between classes with mean classification accuracy of 71.1%. Providing intuitive feedback via sound frees the surgeons' visual attention to remain on the patient, allowing for greater control over diagnostic and surgical tools during surgery, and thus promoting clinical translation of spectroscopic diagnostics.


An instrument for assessing public health system performance: validity in rural settings.
This study evaluated the validity and utility of the Local Public Health System Assessment Instrument (Local Instrument) of the National Public Health Performance Standards Program in rural settings. The study compared the Local Instrument scores of 6 rural local public health systems to external assessments of those public health systems. The 6 public health systems represented 3 states in which 1 of the 2 local jurisdictions had scored well below and the other well above the state median in a pilot test of the Local Instrument. The study design featured a case study approach consisting of an iterative and integrated combination of semistructured individual and focus group interviews along with the collection of archival materials provided by the 6 public health systems. Despite differences in Local Instrument scores, the representative public health systems in each state provided roughly the same levels of public health services. Sites varied tremendously in the percentage of survey items rated highly or less relevant. The National Public Health Performance Standards Program Local Instrument can provide a useful structure and process for assessing public health system performance at the local level. Key informants provided several recommendations to improve the Local Instrument, including clarification of difficult terminology and acronyms, and development of multiple instruments structured around subsets of survey items.


Time Course of Lung Changes at Chest CT during Recovery from Coronavirus Disease 2019 (COVID-19).
Background Chest CT is used to assess the severity of lung involvement in coronavirus disease 2019 (COVID-19). Purpose To determine the changes in chest CT findings associated with COVID-19 from initial diagnosis until patient recovery. Materials and Methods This retrospective review included patients with real-time polymerase chain reaction-confirmed COVID-19 who presented between January 12, 2020, and February 6, 2020. Patients with severe respiratory distress and/or oxygen requirement at any time during the disease course were excluded. Repeat chest CT was performed at approximately 4-day intervals. Each of the five lung lobes was visually scored on a scale of 0 to 5, with 0 indicating no involvement and 5 indicating more than 75% involvement. The total CT score was determined as the sum of lung involvement, ranging from 0 (no involvement) to 25 (maximum involvement). Results Twenty-one patients (six men and 15 women aged 25-63 years) with confirmed COVID-19 were evaluated. A total of 82 chest CT scans were obtained in these patients, with a mean interval (±standard deviation) of 4 days ± 1 (range, 1-8 days). All patients were discharged after a mean hospitalization period of 17 days ± 4 (range, 11-26 days). Maximum lung involved peaked at approximately 10 days (with a calculated total CT score of 6) from the onset of initial symptoms (R2 = 0.25, P < .001). Based on quartiles of chest CT scans from day 0 to day 26 involvement, four stages of lung CT findings were defined. CT scans obtained in stage 1 (0-4 days) showed ground-glass opacities (18 of 24 scans [75%]), with a mean total CT score of 2 ± 2; scans obtained in stage 2 (5-8 days) showed an increase in both the crazy-paving pattern (nine of 17 scans [53%]) and total CT score (mean, 6 ± 4; P = .002); scans obtained in stage 3 (9-13 days) showed consolidation (19 of 21 scans [91%]) and a peak in the total CT score (mean, 7 ± 4); and scans obtained in stage 4 (≥14 days) showed gradual resolution of consolidation (15 of 20 scans [75%]) and a decrease in the total CT score (mean, 6 ± 4) without crazy-paving pattern. Conclusion In patients recovering from coronavirus disease 2019 (without severe respiratory distress during the disease course), lung abnormalities on chest CT scans showed greatest severity approximately 10 days after initial onset of symptoms. © RSNA, 2020.


Developing a scalable training model in global mental health: pilot study of a video-assisted training Program for Generalist Clinicians in Rural Nepal.
In low- and middle-income countries, mental health training often includes sending few generalist clinicians to specialist-led programs for several weeks. Our objective is to develop and test a video-assisted training model addressing the shortcomings of traditional programs that affect scalability: failing to train all clinicians, disrupting clinical services, and depending on specialists. We implemented the program -video lectures and on-site skills training- for all clinicians at a rural Nepali hospital. We used Wilcoxon signed-rank tests to evaluate pre- and post-test change in knowledge (diagnostic criteria, differential diagnosis, and appropriate treatment). We used a series of 'Yes' or 'No' questions to assess attitudes about mental illness, and utilized exact McNemar's test to analyze the proportions of participants who held a specific belief before and after the training. We assessed acceptability and feasibility through key informant interviews and structured feedback. For each topic except depression, there was a statistically significant increase (Δ) in median scores on knowledge questionnaires: Acute Stress Reaction (Δ = 20, p = 0.03), Depression (Δ = 11, p = 0.12), Grief (Δ = 40, p < 0.01), Psychosis (Δ = 22, p = 0.01), and post-traumatic stress disorder (Δ = 20, p = 0.01). The training received high ratings; key informants shared examples and views about the training's positive impact and complementary nature of the program's components. Video lectures and on-site skills training can address the limitations of a conventional training model while being acceptable, feasible, and impactful toward improving knowledge and attitudes of the participants.


Whole-exome sequencing in 20,197 persons for rare variants in Alzheimer's disease.
The genetic bases of Alzheimer's disease remain uncertain. An international effort to fully articulate genetic risks and protective factors is underway with the hope of identifying potential therapeutic targets and preventive strategies. The goal here was to identify and characterize the frequency and impact of rare and ultra-rare variants in Alzheimer's disease, using whole-exome sequencing in 20,197 individuals. We used a gene-based collapsing analysis of loss-of-function ultra-rare variants in a case-control study design with data from the Washington Heights-Inwood Columbia Aging Project, the Alzheimer's Disease Sequencing Project and unrelated individuals from the Institute of Genomic Medicine at Columbia University. We identified 19 cases carrying extremely rare SORL1 loss-of-function variants among a collection of 6,965 cases and a single loss-of-function variant among 13,252 controls (P = 2.17 × 10-8; OR: 36.2 [95% CI: 5.8-1493.0]). Age-at-onset was 7 years earlier for patients with SORL1 qualifying variant compared with noncarriers. No other gene attained a study-wide level of statistical significance, but multiple top-ranked genes, including GRID2IP,WDR76 and GRN, were among candidates for follow-up studies. This study implicates ultra-rare, loss-of-function variants in SORL1 as a significant genetic risk factor for Alzheimer's disease and provides a comprehensive dataset comparing the burden of rare variation in nearly all human genes in Alzheimer's disease cases and controls. This is the first investigation to establish a genome-wide statistically significant association between multiple extremely rare loss-of-function variants in SORL1 and Alzheimer's disease in a large whole-exome study of unrelated cases and controls.


The association between renal replacement therapy modality and long-term outcomes among critically ill adults with acute kidney injury: a retrospective cohort study*.
Among critically ill patients with acute kidney injury, the impact of renal replacement therapy modality on long-term kidney function is unknown. Compared with conventional intermittent hemodialysis, continuous renal replacement therapy may promote kidney recovery by conferring greater hemodynamic stability; yet continuous renal replacement therapy may not enhance patient survival and is resource intense. Our objective was to determine whether continuous renal replacement therapy was associated with a lower risk of chronic dialysis as compared with intermittent hemodialysis, among survivors of acute kidney injury. Retrospective cohort study. Linked population-wide administrative databases in Ontario, Canada. Critically ill adults who initiated dialysis for acute kidney injury between July 1996 and December 2009. In the primary analysis, we considered those who survived to at least 90 days after renal replacement therapy initiation. Initial receipt of continuous renal replacement therapy versus intermittent hemodialysis. Continuous renal replacement therapy recipients were matched 1:1 to intermittent hemodialysis recipients based on a history of chronic kidney disease, receipt of mechanical ventilation, and a propensity score for the likelihood of receiving continuous renal replacement therapy. Cox proportional hazards were used to evaluate the relationship between initial renal replacement therapy modality and the primary outcome of chronic dialysis, defined as the need for dialysis for a consecutive period of 90 days. We identified 2,315 continuous renal replacement therapy recipients of whom 2,004 (87%) were successfully matched to 2,004 intermittent hemodialysis recipients. Participants were followed over a median duration of 3 years. The risk of chronic dialysis was significantly lower among patients who initially received continuous renal replacement therapy versus intermittent hemodialysis (hazard ratio, 0.75; 95% CI, 0.65-0.87). This relation was more prominent among those with preexisting chronic kidney disease (p value for interaction term = 0.065) and heart failure (p value for interaction term = 0.035). Compared with intermittent hemodialysis, initiation of continuous renal replacement therapy in critically ill adults with acute kidney injury is associated with a lower likelihood of chronic dialysis.


Intermittent fasting in the prevention and treatment of cancer.
Chronic caloric restriction (CR) has powerful anticarcinogenic actions in both preclinical and clinical studies but may be difficult to sustain. As an alternative to CR, there has been growing interest in intermittent fasting (IF) in both the scientific and lay community as a result of promising study results, mainly in experimental animal models. According to a survey by the International Food Information Council Foundation, IF has become the most popular diet in the last year, and patients with cancer are seeking advice from oncologists about its beneficial effects for cancer prevention and treatment. However, as discussed in this review, results from IF studies in rodents are controversial and suggest potential detrimental effects in certain oncologic conditions. The effects of IF on human cancer incidence and prognosis remain unknown because of a lack of high-quality randomized clinical trials. Preliminary studies suggest that prolonged fasting in some patients who have cancer is safe and potentially capable of decreasing chemotherapy-related toxicity and tumor growth. However, because additional trials are needed to elucidate the risks and benefits of fasting for patients with cancer, the authors would not currently recommend patients undergoing active cancer treatment partake in IF outside the context of a clinical trial. IF may be considered in adults seeking cancer-prevention benefits through means of weight management, but whether IF itself affects cancer-related metabolic and molecular pathways remains unanswered.


The type II secretion system - a dynamic fiber assembly nanomachine.
Type II secretion systems (T2SSs) share common origins and structure with archaeal flagella (archaella) and pili, bacterial competence systems and type IV pili. All of these systems use a conserved ATP-powered machinery to assemble helical fibers that are anchored in the plasma membrane. The T2SSs assemble pseudopili, periplasmic filaments that promote extracellular secretion of folded periplasmic proteins. Comparative analysis of T2SSs and related fiber assembly nanomachines might provide important clues on their functional specificities and dynamics. This review focuses on recent developments in the study of pseudopilus structure and biogenesis, and discusses mechanistic models of pseudopilus function in protein secretion.


Suicidal behavior in adolescents with comorbid depression and alcohol abuse.
Depression, alcohol abuse and suicidality each continue to threaten adolescent populations throughout the world. The comorbidity between these diseases has been found to be up to 73% with consistent positive correlations between adolescent drinking, depression and suicidality. Alcohol abuse, depression and suicidal behavior in adolescents have also been found to have biochemical and genetic correlates. This article explores the contributing and causative factors and directional models underlying such prevalent comorbidities. Alcohol use is shown to be both a distal and proximal cause of suicide attempts in adolescent populations. Individuals with both alcoholism and depression who attempt or complete suicide often present with significantly high levels of aggression and impulsivity. These factors may be caused or nuanced by poor or underdeveloped coping skills as well as other comorbid psychiatric conditions. Such behaviors, alone or in comorbidity, may be a consequence of childhood abuse, social pressures, low self-esteem and/or delinquency- all of which may be particularly salient among adolescent populations. Such adolescent stressors are implicated as the cause for the self-medication model. Some studies suggest that depression encourages alcohol use as self-medication and then leads to suicidality, while others imply that the initial alcohol consumption is responsible for increasing depressive and suicidal symptoms in adolescents. This article discusses the social stigma associated with alcoholism, depression and suicidality, and how that may serve to enhance these disorders in adolescent populations. Many directional models are presented based on past research and as suggestions for future research. There is a lot that can be done by clinicians, legal and educational professionals and society at large that may help to prevent and treat such problems.


Large-scale screening of circulating microRNAs in individuals with HIV-1 mono-infections reveals specific liver damage signatures.
Human immunodeficiency virus type 1 (HIV-1)-induced inflammation and/or long-term antiretroviral drug toxicity may contribute to the evolution of liver disease. We investigated circulating plasma microRNAs (miRNAs) as potential biomarkers of liver injury in patients mono-infected with HIV-1. We performed large-scale deep sequencing analyses of small RNA level on plasma samples from patients with HIV-1 mono-infection that had elevated or normal levels of alanine aminotransferase (ALT) or focal nodular hyperplasia (FNH). Hepatitis C virus (HCV) mono-infected patients were also studied. Compared to healthy donors, patients with HIV-1 or HCV mono-infections showed significantly altered (fold change >2, adjusted p < 0.05) level of 25 and 70 miRNAs, respectively. Of the 25 altered miRNAs found in patients with HIV-1, 19 were also found in patients mono-infected with HCV. Moreover, 13 of the 14 most up-regulated miRNAs (range: 9.3-3.4-fold increase) in patients with HCV mono-infections were also up-regulated in patients with HIV-1 mono-infections. Importantly, most of these miRNAs significantly and positively correlated with ALT and aspartate aminotransferase (AST) levels, and liver fibrosis stage (p < 0.05). MiR-122-3p and miR-193b-5p were highly up-regulated HIV-1 mono-infected patients with elevated ALT or FNH, but not in HIV-1 patients with normal levels of ALT. These results reveal that HIV-1 infections impacted liver-related miRNA levels in the absence of an HCV co-infection, which highlights the potential of miRNAs as biomarkers for the progression of liver injury in HIV-1 infected patients.


Listening to Lyrica: contested illnesses and pharmaceutical determinism.
Fibromyalgia syndrome is a debilitating pain disorder of unknown origins and a paradigmatic contested illness. As with other contested illnesses, the reality of fibromyalgia is disputed by many physicians. Thus, millions of individuals who are diagnosed with fibromyalgia must cope with chronic symptoms as well as medical and public skepticism. In this context, the U.S. Federal Drug Administration's approval of Lyrica, the first prescription medication specifically for the management of fibromyalgia, is of considerable interest. In this paper I examine the cultural logic whereby the existence (and marketing) of an officially approved prescription medication for a condition lends support to the biomedical existence of the condition itself. I label this logic pharmaceutical determinism and argue that it represents an important new phase in the proliferation of contested illness diagnoses. Using the case of Lyrica, I describe the role that pharmaceutical companies and pharmaceuticals themselves play in promoting and legitimating contested diagnoses and validating those who are so diagnosed. Through a narrative analysis of the Lyrica direct-to-consumer advertising campaign and the responses of fibromyalgia sufferers to the introduction and marketing of Lyrica, I demonstrate the symbiotic relationship between the interests of the pharmaceutical industry, contested illness legitimization, and medicalization. I also provide a gender analysis of this relationship, foregrounding how contested illnesses continue to be shaped by their feminization in a cultural context that equates women with irrationality. Finally, I address the consequences and limitations of relying on the pharmaceutical industry for illness validation.


The effect of calcium ions on the glycolytic activity of Ehrlich ascites-tumour cells.
1. Added Ca(2+) inhibited lactate formation from sugar phosphates by intact Ehrlich ascites-tumour cells. Lactate formation from glucose by these cells was unaffected by added Ca(2+). 2. The Ca(2+) inhibition of lactate formation by intact cells occurred in the extracellular medium. 3. Intact ascites-tumour cells did not take up Ca(2+)in vitro. 4. Glycolysis of sugar phosphates by cell extracts as well as pyruvate formation from 3-phosphoglycerate and phosphoenolpyruvate was inhibited by Ca(2+). 5. It was concluded that Ca(2+) inhibited the pyruvate-kinase (EC 184.108.40.206) reaction. Further, Ca(2+) inhibition of pyruvate kinase could be correlated with the overall inhibition of glycolysis. 6. Concentrations of Ca(2+) usually present in Krebs-Ringer buffers, inhibited glycolysis and pyruvate-kinase activity by approx. 50%. 7. The inhibition of glycolysis by added Ca(2+) could be partially reversed by K(+) and completely reversed by Mg(2+) or by stoicheiometric amounts of EDTA. 8. The hypothesis is advanced that the inability of tumour cells to take up Ca(2+) is a factor contributing towards their high rate of glycolysis.


Nucleosome-Chd1 structure and implications for chromatin remodelling.
Chromatin-remodelling factors change nucleosome positioning and facilitate DNA transcription, replication, and repair. The conserved remodelling factor chromodomain-helicase-DNA binding protein 1(Chd1) can shift nucleosomes and induce regular nucleosome spacing. Chd1 is required for the passage of RNA polymerase IIthrough nucleosomes and for cellular pluripotency. Chd1 contains the DNA-binding domains SANT and SLIDE, a bilobal motor domain that hydrolyses ATP, and a regulatory double chromodomain. Here we report the cryo-electron microscopy structure of Chd1 from the yeast Saccharomyces cerevisiae bound to a nucleosome at a resolution of 4.8 Å. Chd1 detaches two turns of DNA from the histone octamer and binds between the two DNA gyres in a state poised for catalysis. The SANT and SLIDE domains contact detached DNA around superhelical location (SHL) -7 of the first DNA gyre. The ATPase motor binds the second DNA gyre at SHL +2 and is anchored to the N-terminal tail of histone H4, as seen in a recent nucleosome-Snf2 ATPase structure. Comparisons with published results reveal that the double chromodomain swings towards nucleosomal DNA at SHL +1, resulting in ATPase closure. The ATPase can then promote translocation of DNA towards the nucleosome dyad, thereby loosening the first DNA gyre and remodelling the nucleosome. Translocation may involve ratcheting of the two lobes of the ATPase, which is trapped in a pre- or post-translocation state in the absence or presence, respectively, of transition state-mimicking compounds.


Clonally amplified cardiac stem cells are regulated by Sca-1 signaling for efficient cardiovascular regeneration.
Recent studies have shown that cardiac stem cells (CSCs) from the adult mammalian heart can give rise to functional cardiomyocytes; however, the definite surface markers to identify a definitive single entity of CSCs and the molecular mechanisms regulating their growth are so far unknown. Here, we demonstrate a single-cell deposition analysis to isolate individually selected CSCs from adult murine hearts and investigate the signals required for their proliferation and survival. Clonally proliferated CSCs express stem cell antigen-1 (Sca-1) with embryonic stem (ES) cell-like and mesenchymal cell-like characteristics and are associated with telomerase reverse transcriptase (TERT). Using a transgene that expresses a GFP reporter under the control of the TERT promoter, we demonstrated that TERT(GFP)-positive fractions from the heart were enriched for cells expressing Sca-1. Knockdown of Sca-1 transcripts in CSCs led to retarded ex vivo expansion and apoptosis through Akt inactivation. We also show that ongoing CSC proliferation and survival after direct cell-grafting into ischemic myocardium require Sca-1 to upregulate the secreted paracrine effectors that augment neoangiogenesis and limit cardiac apoptosis. Thus, Sca-1 might be an essential component to promote CSC proliferation and survival to directly facilitate early engraftment, and might indirectly exert the effects on late cardiovascular differentiation after CSC transplantation.


B7-CD28/CTLA-4 costimulatory pathways are required for the development of T helper cell 2-mediated allergic airway responses to inhaled antigens.
We have previously demonstrated that the development of allergen-induced airway hyperresponsiveness in a murine model is CD4+ T cell dependent. In the present study, we examined the role of the B7/CD28-CTLA4 costimulatory T cell activation pathway in the pathogenesis of allergen-induced airway hyperresponsiveness in this murine model. Sensitized A/J mice develop significant increases in airway responsiveness, bronchoalveolar lavage eosinophils, serum IgE levels, and Th2-associated cytokine production following aspiration challenge with OVA. Administration of CTLA4-Ig either before Ag sensitization or before pulmonary Ag challenge abolished Ag-induced airway hyperresponsiveness and pulmonary eosinophilia. Examination of cytokine protein levels in the bronchoalveolar lavage showed a significant decrease in the level of the Th2 cytokine, IL-4, after CTLA4-Ig treatment either before sensitization or before challenge, with no significant change in the concentration of the Th1 cytokine, IFN-gamma. Further, the Ag-specific Ab isotypes IgG1 and IgE were significantly decreased in animals treated with CTLA4-Ig before challenge, while there was no significant change in the IgG2a Ab isotype. These data demonstrate that administration of CTLA4-Ig is effective in ablating allergen-induced airway dysfunction concomitant with a significant reduction in the Th2 response. We conclude that B7/CD28-CTLA-4 costimulation is required for the development of many of the immunologic and physiologic features of asthma, possibly by promoting a pathologic type 2-associated response.


Purification of recombinant adeno-associated virus by iodixanol gradient ultracentrifugation allows rapid and reproducible preparation of vector stocks for gene transfer in the nervous system.
Recombinant adeno-associated virus (rAAV) vectors have become attractive tools for in vivo gene transfer. The production and purification of high-titer rAAV vector stocks for experimental and therapeutic gene transfer continue to undergo improvement. Standard rAAV vector purification protocols include the purification of the vector by cesium chloride (CsCl)-density gradient centrifugation followed by extensive desalination via dialysis against a physiological buffer for in vivo use. These procedures are extremely time consuming and frequently result in a substantial loss of the infectious vector titer. As an alternative to CsCl we have investigated the use of Iodixanol, an X-ray contrast solution, as the density-gradient medium. Purification of rAAV vectors by Iodixanol shortened the centrifugation period to 3 hr and resulted in reproducible concentration and purification of rAAV-vector stocks. We show that injection of rAAV derived from an Iodixanol gradient can be used for in vivo gene transfer applications in the brain and spinal cord without detectable cytopathic effects and directing stable transgene expression for at least 2 months.


Leveling the field: addressing health disparities through diabetes disease management.
To examine the relationships among patient characteristics, labor inputs, and improvement in glycosylated hemoglobin (A1C) level in a successful primary care-based diabetes disease management program (DDMP). We performed subanalyses to examine the relationships among patient characteristics, labor inputs, and improvement in A1C level within a randomized controlled trial. Control patients received usual care, while intervention patients received usual care plus a comprehensive DDMP. The primary outcome was improvement in A1C level over 12 months stratified by intervention status and patient characteristics. Process outcomes included the number of actions or contacts with patients, time spent with patients, and number of glucose medication titrations or additions. One hundred ninety-three of 217 enrolled patients (88.9%) had complete 12-month followup data. Patients in the intervention group had significantly greater improvement in A1C level than the control group (-2.1% vs -1.2%, P = .007). In multivariate analysis, no significant differences were observed in improvement in A1C level when stratified by age, race/ethnicity, income, or insurance status, and no interaction effect was observed between any covariate and intervention status. Among intervention patients, we observed similar labor inputs regardless of age, race/ethnicity, sex, education, or whether goal A1C level was achieved. Among intervention patients in a successful DDMP, improvement in A1C level was achieved regardless of age, race/ethnicity, sex, income, education, or insurance status. Labor inputs were similar regardless of age, race/ethnicity, sex, or education and may reflect the nondiscriminatory nature of providing algorithm-based disease management care.


Male and female transsexualism: the Danish experience with 37 patients.
Since the first sex-reassignment operation in Denmark at the Rigshospitalet in 1951, a total of 37 patients, 29 males and 8 females, have had sex-modifying surgery and a change in legal status. In our experience a basic insecure gender identity is a predominant trait in transsexuals, dating back to earliest childhood. This insecurity and a concomitant anxiety are overcome differently by the two transsexual sexes. In male transsexualism, the most outstanding characteristic is a narcissistic withdrawal to a condition marked by submission and pseudofeminity. Anxiety and insecurity are basic to the gender dysphoria but are subdued by means of fantasy escape and gratification in aestheticized ego-ideals with suppression of aggressive and sexual feelings. This results in the often observed pseudofeminity in the male transsexual. A core group of transsexual males are marked by a persistent pseudofeminine narcissism. They have stable ego strength, are agenital in sexual attitude, and have an intact sense of reality. This group is expected to remain so after sex reassignment. The transsexual female assumes a narcissistic, phallic attitude displaying outer activities and caricatured masculine manners in an attempt to subdue her insecurity. Examples are given of the characteristic splitting of these persons' phenomenological ego-experiences and how different their reality testing is from that of psychotic persons with a desire for sex change. Transsexual females are much more sexually active than transsexual males. We find a closer connection between female homosexuality and transsexualism than between male homosexuality and transsexualism.


Does emotion processing require attention? The effects of fear conditioning and perceptual load.
This study examined the impact of perceptual load on the processing of unattended threat-relevant faces. Participants performed a central letter-classification task while ignoring irrelevant face distractors, which appeared above or below the central task. The face distractors were graded for affective salience by means of aversive fear conditioning, with a conditioned angry face (CS+), an unconditioned angry face (CS-), and a neutral control face. The letter-classification task was presented under conditions of both low and high perceptual load. Results showed that fear conditioned (i.e., CS+) angry face distractors interfered with task performance more than CS- angry or neutral face distractors but that this interference was completely eliminated by high perceptual load. These findings demonstrate that aversively conditioned face distractors capture attention only under conditions of low perceptual load.


Evaluation of linear models of surface spectral reflectance with small numbers of parameters.
Recent computational models of color vision demonstrate that it is possible to achieve exact color constancy over a limited range of lights and surfaces described by linear models. The success of these computational models hinges on whether any sizable range of surface spectral reflectances can be described by a linear model with about three parameters. In the first part of this paper, I analyze two large sets of empirical surface spectral reflectances and examine three conjectures concerning constraints on surface reflectance: that empirical surface reflectances fall within a linear model with a small number of parameters, that empirical surface reflectances fall within a linear model composed of band-limited functions with a small number of parameters, and that the shape of the spectral-sensitivity curves of human vision enhance the fit between empirical surface reflectances and a linear model. I conclude that the first and second conjectures hold for the two sets of spectral reflectances analyzed but that the number of parameters required to model the spectral reflectances is five to seven, not three. A reanalysis of the empirical data that takes human visual sensitivity into account gives more promising results. The linear models derived provide excellent fits to the data with as few as three or four parameters, confirming the third conjecture. The results suggest that constraints on possible surface-reflectance functions and the "filtering" properties of the shapes of the spectral-sensitivity curves of photoreceptors can both contribute to color constancy. In the last part of the paper I derive the relation between the number of photoreceptor classes present in vision and the "filtering" properties of each class. The results of this analysis reverse a conclusion reached by Barlow: the "filtering" properties of human photoreceptors are consistent with a trichromatic visual system that is color constant.


Identifying targets for drug discovery using bioinformatics.
Drug discovery is the process of discovering and designing drugs, which includes target identification, target validation, lead identification, lead optimization and introduction of the new drugs to the public. This process is very important, involving analyzing the causes of the diseases and finding ways to tackle them. The problems we must face include: i) that this process is so long and expensive that it might cost millions of dollars and take a dozen years; and ii) the accuracy of identification of targets is not good enough, which in turn delays the process. Introducing bioinformatics into the drug discovery process could contribute much to it. Bioinformatics is a booming subject combining biology with computer science. It can explore the causes of diseases at the molecular level, explain the phenomena of the diseases from the angle of the gene and make use of computer techniques, such as data mining, machine learning and so on, to decrease the scope of analysis and enhance the accuracy of the results so as to reduce the cost and time. Here we describe recent studies about how to apply bioinformatics techniques in the four phases of drug discovery, how these techniques improve the drug discovery process and some possible difficulties that should be dealt with. We conclude that combining bioinformatics with drug discovery is a very promising method although it faces many problems currently.


A reduced liver 18F-FDG uptake may be related to hypoalbuminemia in patients with malnutrition.
18F-FDG PET/CT is a hybrid imaging method widely used as a useful, noninvasive imaging modality for evaluating various neoplastic diseases. When assessing the tumor uptake, the liver and the mediastinal blood pool are often used as a reference region. In daily clinical practice, the 18F-FDG uptake in the liver sometimes appears to decrease on PET images of patients with malnutrition. The purpose of this study was to investigate whether or not the liver 18F-FDG uptake is decreased in patients with malnutrition. We retrospectively analyzed 246 patients who underwent 18F-FDG PET/CT from January 2018 to June 2018 and whose blood serum albumin was measured within 1 month of PET/CT. We compared the liver uptake and mediastinal blood uptake of patients with low serum albumin level (< 4.0 g/dl) and hypoalbuminemia (< 3.5 g/dl) with those with a normal serum albumin level (≥ 4.0 g/dl). Correlations between the liver and mediastinal blood uptake and the serum albumin level were also calculated. The maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean) of the liver in 117 patients with low serum albumin were 3.1 ± 0.5 and 2.3 ± 0.3, respectively, while they were 2.9 ± 0.4, 2.0 ± 0.3 in 29 patients with hypoalbuminemia; these values were all significantly lower than the respective ones (3.4 ± 0.5, 2.5 ± 0.4) in 129 patients with normal serum albumin (all p < 0.001). The SUVmean of the mediastinal blood uptake in patients with hypoalbuminemia and normal serum albumin were 1.6 ± 0.2 and 1.7 ± 0.3, respectively (p = 0.053). The serum albumin level demonstrated a significantly positive, moderate correlation with the liver SUVmean, showing a regression line of y = 0.31x + 1.1 (r = 0.41, p < 0.001). The liver 18F-FDG uptake tended to decrease in patients with hypoalbuminemia. In the patients with malnutrition, the mediastinal blood pool may be a more stable reference than the liver for evaluating the tumor activity because hypoalbuminemia is considered to less strongly influence the mediastinal blood pool than that in the liver.


Cell-specific nitrogen- and carbon-fixation of cyanobacteria in a temperate marine system (Baltic Sea).
We analysed N2 - and carbon (C) fixation in individual cells of Baltic Sea cyanobacteria by combining stable isotope incubations with secondary ion mass spectrometry (SIMS). Specific growth rates based on N2 - and C-fixation were higher for cells of Dolichospermum spp. than for Aphanizomenon sp. and Nodularia spumigena. The cyanobacterial biomass, however, was dominated by Aphanizomenon sp., which contributed most to total N2 -fixation in surface waters of the Northern Baltic Proper. N2 -fixation by Pseudanabaena sp. and colonial picocyanobacteria was not detectable. N2 -fixation by Aphanizomenon sp., Dolichospermum spp. and N. spumigena populations summed up to total N2 -fixation, thus these genera appeared as sole diazotrophs within the Baltic Sea's euphotic zone, while their mean contribution to total C-fixation was 21%. Intriguingly, cell-specific N2 -fixation was eightfold higher at a coastal station compared to an offshore station, revealing coastal zones as habitats with substantial N2 -fixation. At the coastal station, the cell-specific C- to N2 -fixation ratio was below the cellular C:N ratio, i.e. N2 was assimilated in excess to C-fixation, whereas the C- to N2 -fixation ratio exceeded the C:N ratio in offshore sampled diazotrophs. Our findings highlight SIMS as a powerful tool not only for qualitative but also for quantitative N2 -fixation assays in aquatic environments.


Cytolytic T lymphocyte function is independent of growth phase and position in the mitotic cycle.
We have investigated mitotic cell cycle and growth phase regulation of homogeneous cytolytic T lymphocytes (CTL). Two independently derived CTL clones were stained with the DNA-binding dye Hoechst 33342, sorted in a fluorescence-activated cell sorter according to their position in the cell cycle, and then assayed for specific lytic activity using a short-term (30 min) (51)Cr release assay. Results show that lytic activity remained unchanged throughout the cell cycle. Furthermore, there was no significant difference in the lytic activity of CTL clones growing exponentially or arrested in a plateau phase. These results demonstrate that T cell-mediated cytolysis is independent of growth phase and position in the cell cycle.


The Beneficial Effect of Korean Red Ginseng Extract on Atopic Dermatitis Patients: An 8 Weeks Open, Noncomparative Clinical Study.
Atopic dermatitis (AD) is a chronic or chronically relapsing, eczematous, severely pruritic inflammatory skin disorder. Korean red ginseng (KRG) has been shown previously to exhibit diverse biological effects including anti-inflammatory and antipruritic effects in a murine model. We aimed to investigate the beneficial effects of KRG on AD patients, to determine whether there was improvement in disease severity, skin barrier function, pruritus and sleep disturbance relief. An open, noncomparative clinical study that utilized KRG tablets (500 mg/tablet) was conducted. This study included 41 patients with mild to moderate AD diagnosed by the Korean atopic dermatitis guidelines. Three visits to the hospital at days 1, 28±7, and 56±7 for evaluation were made. The effects of KRG were assessed by measuring eczema area and severity index (EASI) score, transepidermal water loss (TEWL), the visual analogue scale (VAS), total amount of topical agents used in recent 8 weeks and investigator global assessment (IGA). Patients taking KRG tablets showed significant decreases in EASI score and TEWL, and the VAS of pruritus and sleep disturbance were significantly reduced. The amount of topical agents used was reduced but not by a statistically significant amount. IGA at the third visit showed improvement of AD compared to the second visit, but the difference was not statistically significant. KRG can be safely used as a health food to achieve clinical improvement of AD as well as improving overall quality of life, and has potential for further development.


Going with the flow: quality-of-life outcomes of cancer survivors with urinary diversion.
The purpose of this descriptive study was to describe health-related quality of life (HRQOL) concerns among cancer patients with continent urinary diversion (UD) and incontinent UD. Study participants were accrued from members of the California United Ostomy Association and 2 cancer centers in Southern California. The City of Hope HRQOL-Ostomy Questionnaire (COHHRQOL-O) is a modified HRQOL measurement tool based on the original work done over a number of years by Grant and colleagues. The COHHRQOL-O was mailed to 2,890 individuals. Of the 1,600 returns, there were 307 responses from patients with UD, indicating that they had a UD and a diagnosis that clearly indicated cancer. The majority of respondents were diagnosed with bladder cancer, and the average time since surgery was 9.5 years. While most patients reported being sexually active prior to UD, less than 27% resumed sexual activity after surgery. More than 75% of patients also reported difficulty in adjusting to their UD, with the majority reporting difficulty with urine leakage. Those who were incontinent reported a range of bothersome issues, such as skin problems around the UD, difficulties in managing UD care, fear of recurrence, financial worries, family distress, and uncertainty about the future. The results of this study add to our understanding of how patients adjust to a UD and what problems and issues can occur, even years after the initial surgery. Mastering UD care is best done under the guidance of a WOC nurse, and access to WOC nurse is essential when problems occur.


Quantitative Proteomics Reveals Ecophysiological Effects of Light and Silver Stress on the Mixotrophic Protist Poterioochromonas malhamensis.
Aquatic environments are heavily impacted by human activities including climate warming and the introduction of xenobiotics. Due to the application of silver nanoparticles as bactericidal agent the introduction of silver into the environment strongly has increased during the past years. Silver ions affect the primary metabolism of algae, in particular photosynthesis. Mixotrophic algae are an interesting test case as they do not exclusively rely on photosynthesis which may attenuate the harmful effect of silver. In order to study the effect of silver ions on mixotrophs, cultures of the chrysophyte Poterioochromonas malhamensis were treated in a replicate design in light and darkness with silver nitrate at a sub-lethal concentration. At five time points samples were taken for the identification and quantitation of proteins by mass spectrometry. In our analysis, relative quantitative protein mass spectrometry has shown to be a useful tool for functional analyses in conjunction with transcriptome reference sequences. A total of 3,952 proteins in 63 samples were identified and quantified, mapping to 4,829 transcripts of the sequenced and assembled transcriptome. Among them, 720 and 104 proteins performing various cellular functions were differentially expressed after eight days in light versus darkness and after three days of silver treatment, respectively. Specifically pathways of the energy and primary carbon metabolism were differentially affected by light and the utilization of expensive reactions hints to an energy surplus of P. malhamensis under light conditions. The excess energy is not invested in growth, but in the synthesis of storage metabolites. The effects of silver were less explicit, observable especially in the dark treatments where the light effect could not mask coinciding but weaker effects of silver. Photosynthesis, particularly the light harvesting complexes, and several sulphur containing enzymes were affected presumably due to a direct interference with the silver ions, mainly affecting energy supply.


Effect of estradiol during culture of bovine oocyte-granulosa cell complexes on the mitochondrial DNA copies of oocytes and telomere length of granulosa cells.
During the development of oocytes from early antral follicles (EAFs) to antral follicles (AFs), the mitochondrial DNA copy number (Mt DNA number) increases, and granulosa cells markedly proliferate. This study examined the effect of supplementation of culture medium with estradiol-17β (E2) on the in vitro growth of oocytes, and increases in the Mt DNA number, and telomere length during the in vitro culture of oocytes derived from EAFs (0.4-0.7 mm in diameter). The E2 supplementation improved antrum formation and the ratio of oocytes reaching the metaphase II (MII) stage, and there was a significant difference in these values between addition E2 concentrations of 10 μg/ml and 0.1 μg/ml. When the oocytes were cultured in the medium containing 10 μg/ml E2, the Mt DNA number determined by real-time polymerase chain reaction (PCR) significantly increased, and the ratio of the Mt DNA number at the end of culture to the Mt DNA number at the beginning of the culture was greatly different among cows, and could be predicted by the degree of the difference between the Mt DNA number of oocytes derived from EAFs and that of oocytes derived from AFs (3-6 mm in diameter). When oocytes were cultured for 16 days in a medium containing 10 μg/ml E2 or 0.1 μg/ml E2, the Mt DNA number of oocytes grown in vitro did not differ, but the telomere length of the granulosa cells was significantly greater in the 10 μg/ml E2 group than in the 0.1 μg/ml group. In conclusion, E2 supplementation in culture medium improved the growth of oocytes derived from EAFs, and a high E2 concentration increased the telomere length of the granulosa cells.


Recurrence rates provide evidence for sex-differential, familial genetic liability for autism spectrum disorders in multiplex families and twins.
Autism spectrum disorders (ASDs) are more prevalent in males, suggesting a multiple threshold liability model in which females are, on average, protected by sex-differential mechanisms. Under this model, autistic females are predicted to carry a more penetrant risk variant load than males and to share this greater genetic liability with their siblings. However, reported ASD recurrence rates have not demonstrated significantly increased risk to siblings of affected girls. Here, we characterize recurrence patterns in multiplex families from the Autism Genetics Resource Exchange (AGRE) to determine if risk in these families follows a female protective model. We assess recurrence rates and quantitative traits in full siblings from 1,120 multiplex nuclear families and concordance rates in 305 twin pairs from AGRE. We consider the first two affected children per family, and one randomly selected autistic twin per pair, as probands. We then compare recurrence rates and phenotypes between males and females and between twin pairs or families with at least one female proband (female-containing (FC)) versus those with only male probands (male-only (MO)). Among children born after two probands, we observe significantly higher recurrence in males (47.5%) than in females (21.1%; relative risk, RR = 2.25; adjusted P = 6.22e-08) and in siblings of female (44.3%) versus siblings of male probands (30.4%; RR = 1.46; adj. P = 0.036). This sex-differential recurrence is also robust in dizygotic twin pairs (males = 61.5%, females = 19.1%; RR = 3.23; adj. P = 7.66e-09). Additionally, we find a significant negative relationship between interbirth interval and ASD recurrence that is driven by children in MO families. By classifying families as MO or FC using two probands instead of one, we observe significant recurrence rate differences between families harboring sex-differential familial liability. However, a significant sex difference in risk to children within FC families suggests that female protective mechanisms are still operative in families carrying high genetic risk loads. Furthermore, the male-specific relationship between shorter interbirth intervals and increased ASD risk is consistent with a potentially greater contribution from environmental factors in males versus higher genetic risk in affected females and their families. Understanding the mechanisms driving these sex-differential risk profiles will be useful for treatment development and prevention.


A Novel Test, the Sternomental Distance Ratio, Used as a Predictor of Difficult Laryngoscopy in a Normal Population and in Thyroid Tumor Surgery Patients: A Preliminary Study.
The aim of the present preliminary study was to assess whether the sternomental distance ratio (SMDR) could be suitable as a predictor of difficult laryngoscopy, in both normal surgical patients and patients scheduled to undergo thyroid tumor surgery. Two hundred and twenty-one consecutive adult patients (among them 122 patients with presumed normal airways and 33 patients with thyroid tumors), scheduled to undergo elective surgery under general anesthesia, were included in this study. Physical and airway characteristics, SMDR, difficult laryngoscopy (using Cormack-Lehane scale) and any kind of assisted intubation were assessed. Decreased SMDR demonstrated a strong correlation with difficult laryngoscopy in both thyroid tumor (Kendall's tau-b -0.578 (P=0.004) and normal patients -0.362 (P<0.001). Difficult laryngoscopy was 0 at SMDR>1.9 and 33% at SMDR <1.55 (P<0.001). The higher the SMDR was, the better the glottic view obtained. ? SMDR>1.9 indicates an easy laryngoscopy, whereas SMDR <1.55 indicates a difficult one in both thyroid tumor and normal patients. SMDR is an objective test to assess difficult airway in thyroid surgery.


Improving the efficiency of genomic selection.
We investigate two approaches to increase the efficiency of phenotypic prediction from genome-wide markers, which is a key step for genomic selection (GS) in plant and animal breeding. The first approach is feature selection based on Markov blankets, which provide a theoretically-sound framework for identifying non-informative markers. Fitting GS models using only the informative markers results in simpler models, which may allow cost savings from reduced genotyping. We show that this is accompanied by no loss, and possibly a small gain, in predictive power for four GS models: partial least squares (PLS), ridge regression, LASSO and elastic net. The second approach is the choice of kinship coefficients for genomic best linear unbiased prediction (GBLUP). We compare kinships based on different combinations of centring and scaling of marker genotypes, and a newly proposed kinship measure that adjusts for linkage disequilibrium (LD). We illustrate the use of both approaches and examine their performances using three real-world data sets with continuous phenotypic traits from plant and animal genetics. We find that elastic net with feature selection and GBLUP using LD-adjusted kinships performed similarly well, and were the best-performing methods in our study.


Injectable hydrogel promotes early survival of induced pluripotent stem cell-derived oligodendrocytes and attenuates longterm teratoma formation in a spinal cord injury model.
Transplantation of pluripotent stem cells and their differentiated progeny has the potential to preserve or regenerate functional pathways and improve function after central nervous system injury. However, their utility has been hampered by poor survival and the potential to form tumors. Peptide-modified biomaterials influence cell adhesion, survival and differentiation in vitro, but their effectiveness in vivo remains uncertain. We synthesized a peptide-modified, minimally invasive, injectable hydrogel comprised of hyaluronan and methylcellulose to enhance the survival and differentiation of human induced pluripotent stem cell-derived oligodendrocyte progenitor cells. Cells were transplanted subacutely after a moderate clip compression rat spinal cord injury. The hydrogel, modified with the RGD peptide and platelet-derived growth factor (PDGF-A), promoted early survival and integration of grafted cells. However, prolific teratoma formation was evident when cells were transplanted in media at longer survival times, indicating that either this cell line or the way in which it was cultured is unsuitable for human use. Interestingly, teratoma formation was attenuated when cells were transplanted in the hydrogel, where most cells differentiated to a glial phenotype. Thus, this hydrogel promoted cell survival and integration, and attenuated teratoma formation by promoting cell differentiation.


A race riot's effect on psychological symptoms.
Certain individually stressful events have been observed to increase the psychological distress of persons affected; reduced psychological distress following other events has been attributed to collective processes, including increased group cohesion. These possibilities are investigated by contrasting reported symptom levels of 938 adults interviewed before, during, and after a racial riot. White suburbanites interviewed after the riot and urban black women interviewed during the riot report significantly fewer psychological symptoms. Hypotheses of seasonal symptom changes, sampling biases, and the absence of symptom changes among relatively unimpaired respondents are rejected, suggesting that reductions in symptom level are associated with the riot. Serious methodological problems are raised by our finding that such events may significantly affect not only rates but also patterns of reported psychological symptoms obtained through epidemiological studies.


The structure of the TLR5-flagellin complex: a new mode of pathogen detection, conserved receptor dimerization for signaling.
Knowledge about how Toll-like receptors (TLRs) recognize pathogenic ligands is critical to understanding how these receptors are activated and to designing therapeutic compounds that target this family of receptors for inflammatory diseases. The crystal structure of TLR5 in complex with its bacterial ligand flagellin revealed that the ligand-binding mode for TLR5 is distinct from that of previously characterized TLRs. Nevertheless, like other TLRs, TLR5 forms a dimer in response to ligand binding. This work contributes to our current knowledge of TLR function and further demonstrates the ability of TLRs to couple versatile ligand recognition to a conserved receptor signaling mechanism.


The prevalence of anisometropia and its associated factors in an adult population from Shahroud, Iran.
The aim of this study was to evaluate the prevalence of anisometropia in an urban adult population in the north of Iran. This cross-sectional study was conducted among the 40-64-year-old population in Shahroud, Iran. Random cluster sampling was applied to select 6,311 people. Following an interview, optometric and ophthalmologic examinations, including objective non-cycloplegic refractions, were carried out. The prevalence of anisometropia was reported according to non-cycloplegic refraction and with cut-off points of 0.50, 1.00, 2.00 and 3.00 D. Of the sampled people, 5,190 (82.2 per cent) took part in the study. After considering exclusion criteria, data from 4,918 participants were included in the final analysis. Most participants were female (57.6 per cent) and the average age (with standard deviation) was 50.7 ± 6.2 years. The prevalence of anisometropia with cut-off points of 0.50, 1.00 and 2.00 D were 23.1 (95%CI: 22.0-24.3), 7.7 (95%CI: 7.0-8.4) and 3.2 per cent (95%CI: 2.7-3.7), respectively. The prevalence of severe anisometropia (3.00 D or more) was 1.9 per cent (95%CI: 1.5-2.3). The odds ratio (OR) of anisometropia was 1.06 times higher for every year of increasing age. The OR of anisometropia in participants with cataract was 2.78 times more than in those without (p < 0.001). Anisometropia was more frequent among participants with unilateral cataract (21.7 per cent) compared to those with bilateral cataract (13.4 per cent). Anisometropia of 1.00 D or more was significantly more prevalent among myopic participants compared to hyperopic participants (13.8 versus 12.7 per cent, p < 0.001) and there was a stronger association between anisometropia and myopia (OR = 2.93) than hyperopia (OR = 2.23). With increasing educational level, the prevalence of anisometropia decreased significantly (p < 0.001). The prevalence of aniso-astigmatism of 1.00 D or more was 11.1 per cent (95%CI: 10.2-11.9). In the present study, the prevalence of anisometropia in Iran was not negligible; however, it is less than in Eastern Asia. Myopia, cataract, age and educational level were associated with anisometropia.


Disentangling the influence of socioeconomic status on differences between African American and white women in unmet medical needs.
We sought to disentangle the relationships between race/ethnicity, socioeconomic status (SES), and unmet medical care needs. Data from the 2003-2004 Community Tracking Study Household Survey were used to examine associations between unmet medical needs and SES among African American and White women. No significant racial/ethnic differences in unmet medical needs (24.8% of Whites, 25.9% of African Americans; P = .59) were detected in bivariate analyses. However, among women with 12 years of education or less, African Americans were less likely than were Whites to report unmet needs (odds ratio [OR] = 0.57; 95% confidence interval [CI] = 0.42, 0.79). Relative to African American women with 12 years of education or less, the odds of unmet needs were 1.69 (95% CI = 1.24, 2.31) and 2.18 (95% CI = 1.25, 3.82) among African American women with 13 to 15 years of education and 16 years of education or more, respectively. In contrast, the relationship between educational level and unmet needs was nonsignificant among White women. Among African American women, the failure to recognize unmet medical needs is related to educational attainment and may be an important driver of health disparities, representing a fruitful area for future interventions.


The cyclin-dependent kinase inhibitor p21 (WAF1) is required for survival of differentiating neuroblastoma cells.
We are employing recent advances in the understanding of the cell cycle to study the inverse relationship between proliferation and neuronal differentiation. Nerve growth factor and aphidicolin, an inhibitor of DNA polymerases, synergistically induce neuronal differentiation of SH-SY5Y neuroblastoma cells and the expression of p21WAF1, an inhibitor of cyclin-dependent kinases. The differentiated cells continue to express p21WAF1, even after removal of aphidicolin from the culture medium. The p21WAF1 protein coimmunoprecipitates with cyclin E and inhibits cyclin E-associated protein kinase activity. Each of three antisense oligonucleotides complementary to p21WAF1 mRNA partially blocks expression of p21WAF1 and promotes programmed cell death. These data indicate that p21WAF1 expression is required for survival of these differentiating neuroblastoma cells. Thus, the problem of neuronal differentiation can now be understood in the context of negative regulators of the cell cycle.


A preclinical evaluation of polypropylene/polylacticacid hybrid meshes for fascial defect repair using a rat abdominal hernia model.
Synthetic mesh surgery for both abdominal and urogenital hernia repair is often unsatisfactory in the long-term due to postoperative complications. We hypothesized that a semi-degradable mesh hybrid may provide more appropriate biocompatibility with comparable mechanical properties. The aim was to compare its in vivo biocompatibility with a commercial polypropylene (PP) mesh. 72 rats were randomly allocated to either our new composite mesh (monofilament PP mesh knitted with polylactic-acid-fibers (PLA)) or to a commercially available PP mesh that was used as a control. 15, 90, and 180 days after implantation into the rat abdomen mesh tissue complexes were analysed for erosion, contraction, foreign body reaction, tissue integration and biomechanical properties. No differences were seen in regard to clinical parameters including erosion, contraction or infection rates between the two groups. Biomechanical properties including breaking load, stiffness and deformation did not show any significant differences between the different materials at any timepoint. Macrophage staining did not reveal any significant differences between the two groups or between timepoints either. In regard to collagen I there was significantly less collagen I in the PP group compared to the PP/ PLA group at day 180. Collagen III did not show any significant differences at any timepoint between the two groups. A PP/PLA hybrid mesh, leaving a low amount of PP after PLA degradation seems to have comparable biomechanical properties like PP at 180 days due to enhanced collagen production without significant differences in erosion, contraction, herniation or infection rates.


Annexin II Light Chain p11 Interacts With ENaC to Increase Functional Activity at the Membrane.
The epithelial Na+ channel (ENaC) provides for Na+ absorption in various types of epithelia including the kidney, lung, and colon where ENaC is localized to the apical membrane to enable Na+ entry into the cell. The degree of Na+ entry via ENaC largely depends on the number of active channels localized to the cell membrane, and is tightly controlled by interactions with ubiquitin ligases, kinases, and G-proteins. While regulation of ENaC endocytosis has been well-studied, relatively little is understood of the proteins that govern ENaC exocytosis. We hypothesized that the annexin II light chain, p11, could participate in the transport of ENaC along the exocytic pathway. Our results demonstrate that all three ENaC channel subunits interacted with p11 in an in vitro binding assay. Furthermore, p11 was able to immunoprecipitate ENaC in epithelial cells. Quantitative mass spectrometry of affinity-purified ENaC-p11 complexes recovered several other trafficking proteins including HSP-90 and annexin A6. We also report that p11 exhibits a robust protein expression in cortical collecting duct epithelial cells. However, the expression of p11 in these cells was not influenced by either short-term or long-term exposure to aldosterone. To determine whether the p11 interaction affected ENaC function, we measured amiloride sensitive Na+ currents in Xenopus oocytes or mammalian epithelia co-expressing ENaC and p11 or a siRNA to p11. Results from these experiments showed that p11 significantly augmented ENaC current, whereas knockdown of p11 decreased current. Further, knockdown of p11 reduced ENaC cell surface population suggesting p11 promotes membrane insertion of ENaC. Overall, our findings reveal a novel protein interaction that controls the number of ENaC channels inserted at the membrane via the exocytic pathway.


Genetic diversity and evolution of the emerging picornavirus Senecavirus A.
Senecavirus A (SVA) is an emerging picornavirus that causes vesicular disease (VD) in swine. The virus has been circulating in swine in the United Stated (USA) since at least 1988, however, since 2014 a marked increase in the number of SVA outbreaks has been observed in swine worldwide. The factors that led to the emergence of SVA remain unknown. Evolutionary changes that accumulated in the SVA genome over the years may have contributed to the recent increase in disease incidence. Here we compared full-genome sequences of historical SVA strains (identified before 2010) from the USA and global contemporary SVA strains (identified after 2011). The results from the genetic analysis revealed 6.32 % genetic divergence between historical and contemporary SVA isolates. Selection pressure analysis revealed that the SVA polyprotein is undergoing selection, with four amino acid (aa) residues located in the VP1 (aa 735), 2A (aa 941), 3C (aa 1547) and 3D (aa 1850) coding regions being under positive/diversifying selection. Several aa substitutions were observed in the structural proteins (VP1, VP2 and VP3) of contemporary SVA isolates when compared to historical SVA strains. Some of these aa substitutions led to changes in the surface electrostatic potential of the structural proteins. This work provides important insights into the molecular evolution and epidemiology of SVA.


Association between obesity and polymorphisms in SEC16B, TMEM18, GNPDA2, BDNF, FAIM2 and MC4R in a Japanese population.
There is evidence that the obesity phenotype in the Caucasian populations is associated with variations in several genes, including neuronal growth regulator 1 (NEGR1), SEC16 homolog B (SCE16B), transmembrane protein 18 (TMEM18), ets variant 5 (ETV5), glucosamine-6-phosphate deaminase 2 (GNPDA2), prolactin (PRL), brain-derived neurotrophic factor (BDNF), mitochondrial carrier homolog 2 (MTCH2), Fas apoptotic inhibitory molecule 2 (FAIM2), SH2B adaptor protein 1 (SH2B1), v-maf musculoaponeurotic fibrosarcoma oncogene homolog (MAF), Niemann-Pick disease, type C1 (NPC1), melanocortin 4 receptor (MC4R) and potassium channel tetramerisation domain containing 15 (KCTD15). To investigate the relationship between obesity and these genes in the Japanese population, we genotyped 27 single-nucleotide polymorphisms (SNPs) in 14 genes from obese subjects (n=1129, body mass index (BMI) > or =30 kg m(-2)) and normal-weight control subjects (n=1736, BMI <25 kg m(-2)). The SNP rs10913469 in SEC16B (P=0.000012) and four SNPs (rs2867125, rs6548238, rs4854344 and rs7561317) in the TMEM18 gene (P=0.00015), all of which were in almost absolute linkage disequilibrium, were significantly associated with obesity in the Japanese population. SNPs in GNPDA2, BDNF, FAIM2 and MC4R genes were marginally associated with obesity (P<0.05). Our data suggest that some SNPs identified by genome-wide association studies in the Caucasians also confer susceptibility to obesity in Japanese subjects.


Increased choroidal thickness in patients with Sturge-Weber syndrome.
With the recent development of enhanced depth imaging spectral-domain optical coherence tomography (SD-OCT), it is now possible to measure choroidal thickness in patients with Sturge-Weber syndrome and detect abnormalities that are not visible as part of the fundus examination. We were successful in imaging at least 1 eye in 12 individuals with Sturge-Weber syndrome using enhanced depth imaging SD-OCT. Eyes were defined as affected if they manifested at least one of the following: darkened choroid, glaucomatous optic nerve damage, or conjunctival hyperemia. None of the participants had a clinically visible choroidal hemangioma. The affected eyes had over twice the choroidal thickness of the unaffected eyes (mean [SD], 697 [337] μm vs 331 [94] μm; P = .004, determined by use of an unpaired t test). For the 6 unilaterally affected participants who had both eyes imaged, the choroidal thickness was greater in the affected eyes than in the unaffected eyes of 5 participants (mean [SD], 672 [311] μm vs 329 [88] μm; P = .01, determined by use of a paired t test). The advent of enhanced depth imaging SD-OCT has allowed us to quantify choroidal thickness in the posterior pole, even in eyes with a markedly thickened choroid, such as those found in individuals with Sturge-Weber syndrome. Spectral-domain OCT has a much higher resolution (5-10 μm) than B-scan ultrasonography (150 μm) and can be used to distinguish between the retina and the choroid. Furthermore, enhanced depth imaging SD-OCT can detect choroidal thickness in eyes without clinically apparent choroidal abnormalities.


Use of traditional medicines and traditional practitioners by children in Indonesia: findings from a national population survey in 2014-2015.
Background: Little data are available about traditional and complementary medicine use in children in the general population in Southeast Asia, including Indonesia. The aim of this investigation was to assess the prevalence of the use of traditional medicines and traditional practitioners in children in a national population-based survey in Indonesia. Methods: The cross-sectional sample included 15,739 children (0-14 years) (median age 7.0 years, inter quartile range =7.0) that took part in the Indonesia Family Life Survey in 2014-2015. Results: The prevalence of use of traditional medicines as a treatment in the past four weeks was 6.2%, vitamins or supplements 19.9%, and over-the-counter modern medicine 61.1%. The prevalence of traditional practitioner use in the past 4 weeks was 3.4%, and the prevalence of the use of traditional medicines and/or traditional practitioner in the past 4 weeks was 8.8%. The purpose of consulting the traditional practitioner was mainly massage (86.8%) and treatment for illness (14.8%). In the adjusted logistic regression analysis, having a birth certificate (as a proxy for better economic status) and poor self-rated health were associated with traditional medicine use. Younger age and poor self-rated health were associated with traditional practitioners use. Conclusion: A high prevalence of traditional medicine use in children in Indonesia was found, and several social factors and poor health status of its use were identified.


Associations between lipid profiles of adolescents and their mothers based on a nationwide health and nutrition survey in South Korea.
Dyslipidaemia is a metabolic disease influenced by environmental and genetic factors. Especially, family history related to genetic background is a strong risk factor of lipid abnormality. The aim of this study is to evaluate the association between the lipid profiles of adolescents and their mothers. A cross-sectional study. The data were derived from the Korea National Health and Nutrition Examination Survey (IV-VI) between 2009 and 2015. 2884 adolescents aged 12-18 years and their mothers were included. Outcome variables were adolescents' lipid levels. Mothers' lipid levels were the interesting variables. The lipid profiles included total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). We identified partial correlation coefficients (r) between the lipids. Multiple linear regressions were performed to identify the amount of change in adolescents' lipid levels for each unit increase of their mothers' lipids. The regression models included various clinical characteristics and health behavioural factors of both adolescents and mothers. The mean levels of adolescents' lipids were 156.6, 83.6, 50.4 and 89.4 mg/dL, respectively for TC, TG, HDL-C and LDL-C. Positive correlations between lipid levels of adolescents and mothers were observed for TC, TG, HDL-C and LDL-C (r, 95% CI: 0.271, 0.236 to 0.304; 0.204, 0.169 to 0.239; 0.289, 0.255 to 0.322; and 0.286, 0.252 to 0.319). The adolescent TC level was increased by 0.23 mg/dL for each unit increase of the mother's TC (SE, 0.02; p<0.001). The beta coefficients were 0.16 (SE, 0.01), 0.24 (SE, 0.02) and 0.24 (SE, 0.02), respectively, in each model of TG, HDL-C and LDL-C (all p<0.001). The linear relationships were significant regardless of sex and mother's characteristics. Mothers' lipid levels are associated with adolescents' lipids; therefore, they can serve as a reference for the screening of adolescent's dyslipidaemia.


A streamlined life cycle assessment of a coal-fired power plant: the South African case study.
Non-renewable energy sources have detrimental environmental effects, which directly and indirectly affect the biosphere as environmental deposits from their use for energy generation exceed a threshold. This study performs a streamlined life cycle assessment (LCA) of a coal-fired plant in South Africa. The cradle-to-grave LCA focuses on the coal cycle to determine hotspots with high environmental impacts in the process. Four impact categories were considered in this study: global warming potential, photochemical ozone creation potential, eutrophication potential, and acidification potential. Coal transportation, coal pulverization, water use, and ash management were identified as hotspots in the coal cycle. The coal process has 95% potential for global warming, 4% potential for eutrophication, 1% potential for acidification, and a negligible percentage for photochemical ozone creation. Susceptibility to climate change, eutrophication, acid rain, soil degradation, and water contamination among others are major concerns of the coal cycle. Outsourcing coal from nearby mines with train as medium of transportation reduces environmental impact. Similarly, the use of mitigation technologies like flue gas desulphurization, carbon capture storage, or selective catalytic reduction will reduce the concentration of the flue gas emitted. Ultimately, substituting the coal process with renewable energy sources will ensure environmental sustainability in South Africa. This study will serve as a good resource for further studies on LCA of coal power plants not only in other African countries but in other developing countries with similar situation.