Modulation of pulmonary fibrosis by IL-13Rα2.
Pulmonary fibrosis is a progressive and fatal disease that involves the remodeling of the distal airspace and the lung parenchyma, which results in compromised gas exchange. The median survival time once diagnosed is less than three years. Interleukin (IL)-13 has been shown to play a role in a number of inflammatory and fibrotic diseases. IL-13 modulates its effector functions via a complex receptor system that includes the IL-4 receptor (R) α, IL-13Rα1, and the IL-13Rα2. IL-13Rα1 binds IL-13 with low affinity, yet, when it forms a complex with IL-4α, it binds with much higher affinity, inducing the effector functions of IL-13. IL-13Rα2 binds IL-13 with high affinity but has a short cytoplasmic tail and has been shown to act as a nonsignaling decoy receptor. Transfection of fibroblasts and epithelial cells with IL-13Rα2 inhibited the IL-13 induction of soluble collagen, TGF-β, and CCL17. Adenoviral overexpression of IL-13Rα2 in the lung reduced bleomycin-induced fibrosis. Our work shows that overexpression of IL-13Rα2 inhibits the IL-13 induction of fibrotic markers in vitro and inhibits bleomycin-induced pulmonary fibrosis. In summary our study highlights the antifibrotic nature of IL-13Ra2.


Generation and characterization of 0.6-THz polarization domain-wall trains in an ultralow-birefringence spun fiber.
Polarization domain-wall (PDW) trains have been generated at a repetition rate of 0.6 THz in an ultralow-birefringence spun optical fiber and measured by use of an adapted frequency-resolved optical gating technique. Characterization of the intensity and the phase of the PDW train shows complete switching between adjacent domains of counterrotating circular polarizations and directly confirms predictions based on numerical simulations of the incoherently coupled nonlinear Schrödinger equations.


How energy funnels from the phycoerythrin antenna complex to photosystem I and photosystem II in cryptophyte Rhodomonas CS24 cells.
We report an investigation of energy migration dynamics in intact cells of the photosynthetic cryptophyte Rhodomonas CS24 using analyses of steady-state and time-resolved fluorescence anisotropy measurements. By fitting a specific model to the fluorescence data, we obtain three time scales (17, 58, and 113 ps) by which the energy is transferred from phycoerythrin 545 (PE545) to the membrane-associated chlorophylls (Chls). We propose that these time scales reflect both an angular distribution of PE545 around the photosystems and the relative orientations of the donor dihydrobiliverdin (DBV) bilin and the acceptor Chl. Contrary to investigations of the isolated antenna complex, it is demonstrated that energy transfer from PE545 does not occur from a single-emitting bilin, but rather both the peripheral dihydrobiliverdin (DBV) chromophores in PE545 appear to be viable donors of excitation energy to the membrane-bound proteins. The model shows an almost equal distribution of excitation energy from PE545 to both photosystem I (PSI) and photosystem II (PSII), whose trap times correspond well to those obtained from experiments on isolated photosystems.


Evaluation of Focused Obstetric Ultrasound Examinations by Health Care Personnel in the Democratic Republic of Congo, Guatemala, Kenya, Pakistan, and Zambia.
Prior studies have suggested that obstetrical (OB) ultrasound in low- and middle-income countries has aided in detection of high-risk conditions, which in turn could improve OB management. We are participating in a cluster-randomized clinical trial of OB ultrasound, which is designed to assess the effect of basic OB ultrasound on maternal mortality, fetal mortality, neonatal mortality, and maternal near-miss in 5 low-income countries. We designed a 2-week course in basic OB ultrasound, followed by 12 weeks of oversight, to train health care professionals with no prior ultrasound experience to perform basic OB ultrasound to screen for high-risk pregnancies. All patients with high-risk pregnancies identified by the trainees were referred to higher-level health facilities where fully trained sonographers confirmed the diagnoses before any actions were taken. Although there have been several published studies on basic OB ultrasound training courses for health care workers in low- and middle-income countries, quality control reporting has been limited. The purpose of this study is to report on quality control results of these trainees. Health care workers trained in similar courses could have an adjunctive role in ultrasound screening for high-risk OB conditions where access to care is limited. After completion of the ultrasound course, 41 trainees in 5 countries performed 3801 ultrasound examinations during a 12-week pilot period. Each examination was reviewed by ultrasound trainers for errors in scanning parameters and errors in diagnosis, using predetermined criteria. Of the 32,480 images comprising the 3801 examinations, 94.8% were rated as satisfactory by the reviewers. There was 99.4% concordance between trainee and reviewer ultrasound diagnosis. The results suggest that trained health care workers could play a role in ultrasound screening for high-risk OB conditions.


A novel subset of CD4(+) T(H)2 memory/effector cells that produce inflammatory IL-17 cytokine and promote the exacerbation of chronic allergic asthma.
The inflammatory cytokine interleukin (IL)-17 is involved in the pathogenesis of allergic diseases. However, the identity and functions of IL-17-producing T cells during the pathogenesis of allergic diseases remain unclear. Here, we report a novel subset of T(H)2 memory/effector cells that coexpress the transcription factors GATA3 and RORγt and coproduce T(H)17 and T(H)2 cytokines. Classical T(H)2 memory/effector cells had the potential to produce IL-17 after stimulation with proinflammatory cytokines IL-1β, IL-6, and IL-21. The number of IL-17-T(H)2 cells was significantly increased in blood of patients with atopic asthma. In a mouse model of allergic lung diseases, IL-17-producing CD4(+) T(H)2 cells were induced in the inflamed lung and persisted as the dominant IL-17-producing T cell population during the chronic stage of asthma. Treating cultured bronchial epithelial cells with IL-17 plus T(H)2 cytokines induced strong up-regulation of chemokine eotaxin-3, Il8, Mip1b, and Groa gene expression. Compared with classical T(H)17 and T(H)2 cells, antigen-specific IL-17-producing T(H)2 cells induced a profound influx of heterogeneous inflammatory leukocytes and exacerbated asthma. Our findings highlight the plasticity of T(H)2 memory cells and suggest that IL-17-producing T(H)2 cells may represent the key pathogenic T(H)2 cells promoting the exacerbation of allergic asthma.


Voxel-based morphometry findings in Alzheimer's disease: neuropsychiatric symptoms and disability correlations - preliminary results.
The role of structural brain changes and their correlations with neuropsychiatric symptoms and disability in Alzheimer's disease are still poorly understood. To establish whether structural changes in grey matter volume in patients with mild Alzheimer's disease are associated with neuropsychiatric symptoms and disability Nineteen Alzheimer's disease patients (9 females; total mean age =75.2 y old +4.7; total mean education level =8.5 y +4.9) underwent a magnetic resonance imaging (MRI) examination and voxel-based morphometry analysis. T1-weighted images were spatially normalized and segmented. Grey matter images were smoothed and analyzed using a multiple regression design. The results were corrected for multiple comparisons. The Neuropsychiatric Inventory was used to evaluate the neuropsychiatric symptoms, and the Functional Activities Questionnaire and Disability Assessment for Dementia were used for functional evaluation A significant negative correlation was found between the bilateral middle frontal gyri, left inferior temporal gyrus, right orbitofrontal gyrus, and Neuropsychiatric Inventory scores. A negative correlation was found between bilateral middle temporal gyri, left hippocampus, bilateral fusiform gyri, and the Functional Activities Questionnaire. There was a positive correlation between the right amygdala, bilateral fusiform gyri, right anterior insula, left inferior and middle temporal gyri, right superior temporal gyrus, and Disability Assessment for Dementia scores The results suggest that the neuropsychiatric symptoms observed in Alzheimer's disease patients could be mainly due to frontal structural abnormalities, whereas disability could be associated with reductions in temporal structures.


Seroprevalance Anti-Toxoplasma gondii antibodies in children and adolescents with tourette syndrome/chronic motor or vocal tic disorder: A case-control study.
Toxoplasma gondii infection may be associated with psychiatric disorders due to its neurological effects. The purpose of this study was to investigate the relation between tic disorders in children and adolescents and Anti-Toxoplasma IgG. 43 children diagnosed with Tourette's syndrome(TS) and 87 with chronic motor or vocal tic disorder(CMVTD), and 130 healthy volunteers, all aged 7-18, were enrolled. Anti-Toxoplasma IgG antibody levels obtained from blood specimens were investigated. Toxoplasma IgG positivity was determined in 16(37.2%) of the patients with TS, in 27(31%) of those with CMVTD and in 12(9.2%) members of the control group. Anti-Toxoplasma gondii antibody positivity was 5.827-fold higher in subjects with TS and 4.425-fold higher in subjects with CMVTD compared to the control group. Correlation was determined between a diagnosis of TS or CMVTD and Anti-Toxoplasma gondii antibodies. We think that it will be useful for the neuropsychiatric process associated with Anti-Toxoplasma gondii antibodies to be clarified.


Vision in microalgae.
Flagellate green algae such as Chlamydomonas and related genera are guided by their eyes to places where light conditions are optimal for photosynthetic growth. These eyes constitute the simplest and most common visual system found in nature. The eyes contain optics, photoreceptors and the elementary components of a signal-transduction chain. Rhodopsin serves as the photoreceptor, as it does in animal vision. Upon light stimulation, its all-trans-retinal chromophore isomerizes into 13-cis and activates a photoreceptor channel which leads to a rapid Ca2+ influx into the eyespot region. At low light levels, the depolarization activates small flagellar currents which induce in both flagella small but slightly different beating changes resulting in distinct directional changes. In continuous light, Ca2+ fluxes serve as the molecular basis for phototaxis. In response to flashes of higher energy the larger photoreceptor currents trigger a massive Ca2+ influx into the flagella which causes the well-known phobic response. The identification of proteins contributing to this signalling system has just begun with the isolation and cloning of the opsins from Chlamydomonas and Volvox. These plant opsins are highly charged, are not typical seven-helix receptors, and are believed to form a protein complex with the photoreceptor channel. In Spermatozopsis, a G-protein has been found which interacts either directly with the rhodopsin or with the rhodopsin-ion channel complex. By using insertional mutagenesis, genes coding for proteins that are involved in signalling have been tagged. One of them is connected to the flagellar channel and crucial for the flagellar action potential. Elucidation of photoreception in flagellated algae will provide deeper insight into the development of visual systems, starting from single-celled organisms and moving up through higher animals.


Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study.
Nearly 30,000 patients with coronavirus disease-2019 (COVID-19) have been hospitalized in New York City as of April 14th, 2020. Data on the epidemiology, clinical course, and outcomes of critically ill patients with COVID-19 in this setting are needed. We prospectively collected clinical, biomarker, and treatment data on critically ill adults with laboratory-confirmed-COVID-19 admitted to two hospitals in northern Manhattan between March 2nd and April 1st, 2020. The primary outcome was in-hospital mortality. Secondary outcomes included frequency and duration of invasive mechanical ventilation, frequency of vasopressor use and renal-replacement-therapy, and time to clinical deterioration following hospital admission. The relationship between clinical risk factors, biomarkers, and in-hospital mortality was modeled using Cox-proportional-hazards regression. Each patient had at least 14 days of observation. Of 1,150 adults hospitalized with COVID-19 during the study period, 257 (22%) were critically ill. The median age was 62 years (interquartile range [IQR] 51-72); 170 (66%) were male. Two-hundred twelve (82%) had at least one chronic illness, the most common of which were hypertension (63%; 162/257) and diabetes mellitus (36%; 92/257). One-hundred-thirty-eight patients (54%) were obese, and 13 (5%) were healthcare workers. As of April 14th, 2020, in-hospital mortality was 33% (86/257); 47% (122/257) of patients remained hospitalized. Two-hundred-one (79%) patients received invasive mechanical ventilation (median 13 days [IQR 9-17]), and 54% (138/257) and 29% (75/257) required vasopressors and renal-replacement-therapy, respectively. The median time to clinical deterioration following hospital admission was 3 days (IQR 1-6). Older age, hypertension, chronic lung disease, and higher concentrations of interleukin-6 and d-dimer at admission were independently associated with in-hospital mortality. Critical illness among patients hospitalized with COVID-19 in New York City is common and associated with a high frequency of invasive mechanical ventilation, extra-pulmonary organ dysfunction, and substantial in-hospital mortality.


Advances in the understanding of mineral and bone metabolism in inflammatory bowel diseases.
Chronic inflammatory disorders such as inflammatory bowel diseases (IBDs) affect bone metabolism and are frequently associated with the presence of osteopenia, osteoporosis, and increased risk of fractures. Although several mechanisms may contribute to skeletal abnormalities in IBD patients, inflammation and inflammatory mediators such as TNF, IL-1β, and IL-6 may be the most critical. It is not clear whether the changes in bone metabolism leading to decreased mineral density are the result of decreased bone formation, increased bone resorption, or both, with varying results reported in experimental models of IBD and in pediatric and adult IBD patients. New data, including our own, challenge the conventional views, and contributes to the unraveling of an increasingly complex network of interactions leading to the inflammation-associated bone loss. Since nutritional interventions (dietary calcium and vitamin D supplementation) are of limited efficacy in IBD patients, understanding the pathophysiology of osteopenia and osteoporosis in Crohn's disease and ulcerative colitis is critical for the correct choice of available treatments or the development of new targeted therapies. In this review, we discuss current concepts explaining the effects of inflammation, inflammatory mediators and their signaling effectors on calcium and phosphate homeostasis, osteoblast and osteoclast function, and the potential limitations of vitamin D used as an immunomodulator and anabolic hormone in IBD.


The sharp slowdown in growth of medical imaging: an early analysis suggests combination of policies was the cause.
The growth in the use of advanced imaging for Medicare beneficiaries decelerated in 2006 and 2007, ending a decade of growth that had exceeded 6 percent annually. The slowdown raises three questions. Did the slowdown in growth of imaging under Medicare persist and extend to the non-Medicare insured? What factors caused the slowdown? Was the slowdown good or bad for patients? Using claims file data and interviews with health care professionals, we found that the growth of imaging use among both Medicare beneficiaries and the non-Medicare insured slowed to 1-3 percent per year through 2009. One by-product of this deceleration in imaging growth was a weaker market for radiologists, who until recently could demand top salaries. The expansion of prior authorization, increased cost sharing, and other policies appear to have contributed to the slowdown. A meaningful fraction of the reduction in use involved imaging studies previously identified as having unproven medical value. What has occurred in the imaging field suggests incentive-based cost control measures can be a useful complement to comparative effectiveness research when a procedure's ultimate clinical benefit is uncertain.


[Demanding respect for the subjectivity of public health system clients: towards humanization of health care].
This paper analyzes how clients of the public health system in Natal, Rio Grande do Norte, Brazil, "give meaning" to their situation as "patients", basically focusing on three aspects: (1) evaluation of care, (2) awareness of their rights as citizens and role in improvement of the service, and (3) expectations regarding the encounter with health professionals. The results point to many deficiencies in the health system, besides demonstrating the population's passivity and resignation towards the present situation. The need to consider clients' subjectivity is important, as is the health professional-client relationship, with their encounter considered a prime moment for establishing a humanizing process in health practice, besides fostering the development of a critical awareness among clients concerning their rights and their role as agents of change in the health system.


Late-life Depression, Suicidal Ideation, and Attempted Suicide: The Role of Individual Differences in Maximizing, Regret, and Negative Decision Outcomes.
Suicide rates are highest in adults of middle and older age. Research with psychiatric patients has shown that proneness to feel regret about past decisions can grow so intense that suicide becomes a tempting escape. Here, we examine the additional role of individual differences in maximizing, or the tendency to strive for the best decision, rather than one that is good enough. We provided individual-differences measures of maximizing, regret proneness, and negative life decision outcomes (as reported on the Decision Outcome Inventory or DOI) to a non-psychiatric control group, as well as three groups of psychiatric patients in treatment for suicide attempts, suicidal ideation, or non-suicidal depression. We found that scores on the three individual-differences measures were worse for psychiatric patients than for non-psychiatric controls, and were correlated to clinical assessments of depression, hopelessness, and suicidal ideation. More importantly, maximizing was associated with these clinical assessments, even after taking into account maximizers' worse life decision outcomes. Regret proneness significantly mediated those relationships, suggesting that maximizers could be at risk for clinical depression because of their proneness to regret. We discuss the theoretical relevance of our findings and their promise for clinical practice. Ultimately, late-life depression and suicidal ideation may be treated with interventions that promote better decision making and regret regulation.


NGF expression in the aged rat pineal gland does not correlate with loss of sympathetic axonal branches and varicosities.
The factors that determine the ability of some, but not all neurons, to sustain their axonal projections during aging remain largely unknown. Because sympathetic neurons remain responsive to nerve growth factor (NGF) in old age, it has been proposed that the selective decrease observed in the sympathetic innervation to some targets in aged rats may be the result of a deficit in target-derived NGF. In this study we utilized two different techniques to demonstrate decreased target innervation by sympathetic fibers in the aged rat pineal gland, which is an appropriate and relevant model for examining mechanisms of neuron-target interactions in aging. Tyrosine hydroxylase immunoreactive profiles were quantified in pineal glands of young and aged male Sprague-Dawley rats. The density of tyrosine hydroxylase-immunoreactive fibers was 30% lower in aged pineals, although the remaining fibers contained 20% more tyrosine hydroxylase-immunoreactivity. Othograde tracing of the pineal sympathetic innervation using biotinylated dextran revealed that average axon length, varicosity numbers, branch point numbers, and numbers of terminations were all decreased by approximately 50% in aged tissues, indicating possible functional deficits. These findings suggest that whole branches, along with their associated varicosities were lost in old age. A sensitive quantitative ribonuclease protection assay and a two-site ELISA assay were used to examine whether reduced NGF availability might correlate with sympathetic nerve atrophy. No significant differences were detected in either NGF mRNA or NGF protein levels when comparing young and aged pineal glands, suggesting that atrophy in aged sympathetic neurons is not causally related to reduced availability of NGF at the target. Our results indicate that mechanisms other than NGF expression need to be explored in order to explain the age-related axonal regression observed in this target.


Association between unmet healthcare needs and health-related quality of life: a longitudinal study.
As life expectancy has increased overall, health-related quality of life is now more important than ever. This is especially relevant in countries such as South Korea that are concerned about unmet healthcare needs and health-related quality of life (HRQoL). Thus, we investigated the relationship between unmet healthcare needs and HRQoL in the general population. We used data from the 2011 to 2013 Korea Health Panel Survey, which included data from 8150 baseline participants of 19 years of age or older. We measured HRQoL using the EQ-5D and EQ-VAS indices. In addition, we used generalized estimating equations to perform a longitudinal regression analysis. Approximately 13.1% of the participants (n = 1068) experienced unmet healthcare needs. Individuals with unmet healthcare needs due to economic hardship tended to have lower values than those without unmet healthcare needs for EQ-5D and EQ-VAS indices (EQ-5D: -2.688, P < 0.0001; EQ-VAS: -5.256, P < 0.0001). Additionally, when stratified by gender, both male and female subjects who had unmet healthcare needs and low economic status had a drastic decrease in HRQoL regardless of the reasons for their unmet healthcare needs. Unmet healthcare needs influences HRQoL, which was more pronounced in economically vulnerable groups. Thus, interventions to address HRQoL problems should focus on implementing a guarantee of healthcare services for economically vulnerable groups.


Comparison of Transradial and Transfemoral Approaches in Women Undergoing Percutaneous Coronary Intervention in China: A Retrospective Observational Study.
Despite increasing adoption of the transradial approach for percutaneous coronary intervention (PCI) in clinical practice, the role of transradial intervention (TRI) in women remains a significant debate. We identified 1392 women from a consecutive cohort of patients undergoing PCI in China in 2010 and compared the efficacy and hospital costs between TRI and transfemoral intervention. An inverse probability weighting (IPW) method was used to control for potential bias. After IPW adjustment, patients receiving TRI were less likely to experience post-PCI bleeding (adjusted odds ratio [OR]: 0.46, 95% confidence interval [CI]: 0.30-0.71) and major adverse cardiac events (adjusted OR 0.35, 95% CI 0.19-0.63) and more likely to have shorter length of stay in hospital (1.2 days difference, 95% CI: 0.6-1.7). Moreover, TRI was associated with a cost saving of ¥ (Yuan Renminbi) 7474 (approximately US$1150, 95% CI: ¥2993-¥11 624). More than 70% of this saving was driven by lower PCI-related costs. In conclusion, the use of TRI in women was associated with more favorable outcomes and lower hospital costs.


A prospective study of gestation and birthweight in Aboriginal pregnancies in far north Queensland.
This study aimed to determine the cause(s) of the increased incidence of low birthweight birth in Aboriginal pregnancies. The study prospectively examined a cohort of Aboriginal women presenting for antenatal care before 20 weeks gestation (ultrasound proven) and a reference cohort of Caucasian women in four remote North Queensland communities served by the Far North Regional Obstetric and Gynaecological Service (FROGS) and the antenatal clinic at Cairns Base Hospital. Women with no known medical factors affecting fetal growth or gestation were recruited. Of the 102 Aboriginal and 101 Caucasian women recruited, 96 Aboriginal and 96 Caucasian women completed the study, providing groups of sufficient size to allow statistical assessment at 80% power and 95% significance. Outcomes measured were gestation at delivery, planned or spontaneous birth, neonatal anthropometric measurements and Dubowitz score. The phenotypic and demographic characteristics of the women, their pregnancies, and their babies were also compared to understand the major associations with low birthweight birth in the Aboriginal women. Apart from Aboriginal ethnicity, excessive alcohol use in pregnancy, low maternal body mass index (BMI), and low maternal age had significant negative correlations with birthweight, and excessive tobacco use in pregnancy and high maternal gravidity showed strong similar trends. Culturally appropriate programs need to be funded and developed to reduce the incidence of low birthweight Aboriginal birth, rather than medical programs primarily aimed at the reduction of the incidence of preterm labour.


Pilots and athletes: Different concerns, similar concussion non-disclosure.
Concussion non-disclosure research has focused almost exclusively on athletes. The focus on athletic populations has been sensible considering athletes' demonstrated susceptibility to sustaining and concealing concussions. Nevertheless, the habitual use of athletic populations has allowed researchers and practitioners to omit the development of generalized perceived costs and perceived rewards as critical determinants of concussion self-disclosure. We hypothesized that perceiving concussion disclosure as generally more costly than rewarding would predict negative attitudes towards disclosure and decreased intent to disclose. We also hypothesized that generalized perceived costs and rewards could explain concussion non-disclosure in different populations, athletes and future pilots specifically, even when those populations perceive concussion self-disclosure as costly for different specific reasons. We examined concussion disclosure using 2,504 cadets at the United States Air Force Academy. Cadets completed anonymous surveys assessing their intention to self-disclose undiagnosed concussions (Anticipated Concussion Disclosure) as well as several variables potentially related to concussion self-disclosure: perceived cost, perceived reward, personal identity, attitudes, normative behavior, social support, and self-efficacy. The results demonstrate that concussion non-disclosure develops when a population perceives disclosure as more costly (i.e. directly or emotionally) and less rewarding. Perceived Cost and Perceived Reward variables alone accounted for 50% of the variance in Anticipated Conclusion Disclosure (Adjusted R2 = 0.50, F(2,2312) = 1,145.31, p < 0.001). As expected, Anticipated Conclusion Disclosure developed for different reasons within different sub-populations. Consistent with existing research, cadet intercollegiate athletes reported being primarily concerned that concussion self-disclosure would cause them to miss practice or game time (t (736.7) = 14.20, p < .001, Cohen's d = 0.96). In contrast, cadet future pilots reported being primarily concerned that concussion self-disclosure would have negative United States Air Force career repercussions (t (1828) = 10.25, p < .001, Cohen's d = 0.50). These results suggest that cultures of concussion non-disclosure can develop in any population where disclosure is perceived as having undesirable consequences, not just athletic populations. Concussion researchers and practitioners should devote more attention to the perceived cost-benefit structures that create concussion non-disclosure to address this crucial public health issue more effectively.


Identification of 3-chloro-1,2-propandiol using molecularly imprinted composite solid-phase extraction materials.
A novel molecularly imprinted material based on silica microparticles was synthesized by surface polymerization with 3-chloro-1,2-propandiol (3-MCPD) as a template molecule. The molecularly imprinted polymer (MIP) was characterized by infrared spectroscopy and scanning electron microscopy. The adsorption of 3-MCPD by MIP was measured by gas chromatography with electron capture detection (GC-ECD) and an equilibrium binding experiment. Scatchard analysis revealed that the maximum apparent binding capacities of the MIP and non-imprinted polymer (NIP) were 67.64 and 23.31 μmol/g, respectively. The new adsorbent was successfully used in solid-phase extraction (SPE) to selectively enrich and determine 3-MCPD in soy sauce samples. The MIP-SPE column achieves recoveries higher than 92.7% with a relative standard deviation of less than 1.83%. The MIP-SPE-GC protocol improved the selectivity and eliminated the effects of template leakage on quantitative analysis and could be used for the determination of 3-MCPD in other complex food samples.


Comprehensive assessment of variation at the transforming growth factor beta type 1 receptor locus and colorectal cancer predisposition.
The role of transforming growth factor beta receptor type 1 (TGFBR1) polymorphisms, particularly a coding CGC insertion (rs11466445, TGFBR1*6A/9A) in exon 1, has been extensively investigated in regard to colorectal cancer (CRC) risk. These investigations have generated conflicting results. More recently, allele-specific expression (ASE) of TGFBR1 mRNA has been suggested as predisposing to CRC, with a relative risk of nearly 10-fold and a population attributable risk of approximately 10%. Owing to the potential importance of TGFBR1 variants in CRC, we performed a comprehensive examination of tagging SNPs at and around the gene in 3,101 CRC cases and 3,334 controls of northern European ancestry. To test whether rare or subpolymorphic TGFBR1 variants were associated with CRC risk, we sequenced the gene's exons in a subset of patients. We also evaluated TGFBR1 ASE in a panel of CRC cases and controls. Overall, we found no association between TGFBR1 polymorphisms and CRC risk. The rare variant screen did not identify any changes of potentially pathogenic effects. No evidence of greater ASE in cases than controls was detected, and no haplotype around TGFBR1 could account for the ASE reported in other studies. We conclude that neither genetic variation nor ASE at TGFBR1 is likely to be a major CRC risk factor.


Erythema nodosum.
An active duty female Sailor reports to your clinic complaining of tender nodules to her legs beginning 1.5 weeks ago. She is diagnosed with erythema nodosum (EN), a painful disorder of the subcutaneous fat that is usually self-limited but may be a clue to an additional underlying medical diagnosis. This article reviews the pathophysiology, causes, course, diagnosis, and management of EN.


Consecutive esotropia in intermittent exotropia patients with immediate postoperative overcorrection more than 17 prism diopters.
To report the incidence and the factors of consecutive esotropia (ET) in patients with immediate postoperative overcorrection of at least 17 prism diopters (PD) after surgery for intermittent exotropia (X(T)). Four-hundred-five patients under the age of 18 were included in this study. They underwent bilateral lateral rectus recession (LROU-rec) or unilateral recession-resection (R&R) for X(T). On postoperative day one, the patients with at least 17 PD overcorrection were classified as group 1 and those with less than 17 PD as group 2. Age, refractive error, type of surgery, lateral incomitancy, and the incidence of consecutive ET were analyzed for each group. Group 1 consisted of 116 patients (28.6%) and group 2 consisted of 289 (71.4%). At the six-month follow-up visit, consecutive ET had developed in 16 patients (13.8%) in group 1, and in five patients (1.7%) in group 2 (p<0.001). The occurrence of consecutive ET was not related to age at the time of surgery (p=0.46 in group 1; p=0.54 in group 2), refractive error (p=0.18 in group 1; p=0.08 in group 2), or the type of surgery (p=0.69 in group 1; p=1.00 in group 2). The incidence in group 1 was 23.8% in patients with lateral incomitancy and 8.1% in patients without lateral incomitancy (p<0.05). In group 2, the incidence was 4.4% in patients with lateral incomitancy and 0.5% in patients without lateral incomitancy (p=0.04). Consecutive ET developed in 13.8% of patients with immediate overcorrection of at least 17 PD. Lateral incomitancy was the most important risk factor.


A variant within the DNA repair gene XRCC3 is associated with the development of melanoma skin cancer.
Exposure to UV radiation is a major risk factor for the development of malignant melanoma. DNA damage caused by UV radiation is thought to play a major role in carcinogenesis induction. Multiprotein pathways involved in repairing UV-DNA damage are the base excision, the nucleotide excision, and the homologous double-stranded DNA repair pathways. This study used a sequence-specific primer PCR (PCR-SSP) genotyping method to investigate the association between polymorphisms in DNA repair genes from these pathways with the development of malignant melanoma. The patient cohort was comprised of 125 individuals with malignant melanoma with lesions or staging suggesting a high risk of relapse or metastatic disease. The control population consisted of 211 individuals. We found the presence of a T allele in exon 7 (position 18067) of the XRCC3 gene was significantly associated with melanoma development (P = 0.004; odds ratio, 2.36; relative risk, 1.74). This gene codes for a protein involved in the homologous pathway of double-stranded DNA repair, thought to repair chromosomal fragmentation, translocations, and deletions. These results may provide further insights into the pathogenesis and the mechanism of UV-radiation induced carcinogenesis as well as having a role in prevention.


Computation time-saving mirror image suppression method in Fourier-domain optical coherence tomography.
The theory and experimental results of a computation time-saving mirror image suppression method in Fourier-domain optical coherence tomography, which utilizes the property of reversed system phase shift between the real and mirror images, for differentiating one from the other are demonstrated. By solving a set of two equations based on a reasonable approximation, the real image signal can be obtained. The theoretical backgrounds and the improved real image quality of the average and iteration procedures in this method are particularly illustrated. Also, the mirror image suppression ratios under various process conditions, including different process iteration numbers and different system phase shifts between two neighboring A-mode scans, are evaluated. Meanwhile, the mirror image suppression results based on our method are compared with those obtained from the widely used BM-scan technique. It is found that when a process procedure of two iterations is used, the mirror image suppression quality based on our method can be higher than that obtained from the BM-scan technique. The computation time of our method is significantly shorter than that of the BM-scan technique.


Drug safety testing, disposals and dealing in an English field: Exploring the operational and behavioural outcomes of the UK's first onsite 'drug checking' service.
In a year when UK drug-related deaths and festival drug-related deaths reached their highest on record, a pilot festival drug safety testing service was introduced with the aim of reducing drug-related harm. This paper describes the operational and behavioural outcomes of this pilot and explores the relationship between drug use, supply and policing within festival grounds. Chemists in a temporary laboratory analysed 247 substances submitted by the public to a free, confidential testing service across four days at a UK festival in July 2016. Test results were returned to service users embedded in 230 healthcare consultations delivered to approximately 900 festival-goers (one in five drug using festival-goers) that included harm reduction advice and the opportunity to use a disposal service for further substances of concern. Consultation data were collected at point of care, matched with test results, coded and analysed using SPSS RESULTS: Test results revealed that one in five substances was not as sold or acquired. One in five service users utilised the disposal service for further substances of concern in their possession and another one in six moderated their consumption. Two thirds of those whose sample was missold disposed of further substances, compared with under one in ten whose sample was as sold. Service users who acquired substances onsite at the festival were more than twice as likely to have been missold them as those acquired offsite, were nearly twice as likely to use the disposal service and were on average two years younger. Women were more likely to be using the drug for the first time and more likely to use the disposal service. Test results were shared with emergency services; alerts issued across site and an unanticipated feedback loop occurred to some drug suppliers. This pilot suggests that festival-goers engage productively with onsite drug safety testing services when given the opportunity, such services can access harder-to-reach and new user groups and can play a part in reducing drug-related harm by identifying and informing service users, emergency services and offsite drug using communities about substances of concern. Disposals to the testing service for onward police destruction provide an externally corroborated measure of impact, reducing harm to the individual and others by removing such substances from site. Evidence of differential dealing onsite and its potential negative consequences has implications for future research and policing.


Total fundoplication is superior to partial fundoplication even when esophageal peristalsis is weak.
About a decade ago, partial (240 degrees) fundoplication became popular for treating gastroesophageal reflux disease in cases where the patient's primary esophageal peristalsis was weak. A total (360 degrees) fundoplication was reserved for patients with normal peristalsis (tailored approach). The theory was that partial fundoplication was an adequate antireflux measure, and by posing less resistance for the weak esophageal peristalsis to overcome, it would give rise to less dysphagia. Short-term results seemed to confirm these ideas. This study reports the longterm followup of patients in whom a tailored approach (type of wrap chosen to match esophageal peristalsis) was used, and the results of a nonselective approach, using a total fundoplication regardless of the amplitude of esophageal peristalsis. We analyzed clinical and laboratory findings in 357 patients who had an operation for gastroesophageal reflux disease between October 1992 and November 2002. Group 1 was composed of 235 patients in whom a tailored approach was used between October 1992 and December 1999 (141 patients, partial fundoplication and 94 patients, total fundoplication). Group 2 contained 122 patients in whom a nonselective approach was used (total fundoplication regardless of quality of peristalsis). In group 1, heartburn from reflux (ie, pH monitoring test was abnormal) recurred in 19% of patients after partial fundoplication and in 4% after total fundoplication. In group 2, heartburn recurred in 4% of patients after total fundoplication. The incidence of postoperative dysphagia was similar in the two groups. These data show that laparoscopic partial fundoplication was less effective than total fundoplication in curing gastroesophageal reflux disease, and compared with a partial (240 degrees) fundoplication, a total (360 degrees) fundoplication was not followed by more dysphagia, even when esophageal peristalsis was weak.


Cytokine concentrations direct endothelial function in pregnancy and preeclampsia.
Endothelial dysfunction is a prominent feature of preeclampsia, a hypertensive disorder of pregnancy, and contributes to multiple symptoms characteristic of the syndrome. A myriad of growth factors and cytokines are dysregulated in preeclampsia as compared to normal pregnancy, however, a complete appreciation of the effect of changing concentrations of these factors on endothelial function is lacking. In this study, we evaluate the effect of a variety of growth factors and cytokines on Ca2+ signaling and monolayer integrity. We report that VEGF165, TNFα, EGF, and IL-1β either improve or inhibit Ca2+ signaling depending on dose, whereas TNFα and IL-1β reduce monolayer integrity and bFGF increases monolayer integrity. Additionally, to model the effects of combinations of growth factors and cytokines, we screened for Ca2+ signaling changes in response to 16 dose combinations of VEGF165 and TNFα together. This revealed an optimal combination capable of supporting pregnancy-adapted Ca2+ signaling, and that changes in either VEGF165 or TNFα dose would result in a shift toward suppressed function. This study shows in detail how growth factor or cytokine concentration effects endothelial cell function. Such data can be used to model how changing growth factor and cytokine levels in normal pregnancy may contribute to healthy endothelial function and in preeclampsia may promote endothelial dysfunction. The results of VEGF165 and TNFα combination treatments suggest that more complex growth factor and cytokine combination modeling may be important in order to more accurately understand the effects of circulating factors on the endothelial function.


Risk factors for unfavorable pregnancy outcome in women with adverse childhood experiences.
To explore the association between childhood sexual abuse (CSA), physical abuse, as well as other adverse childhood experiences (ACE), and different obstetrical risk factors/behaviors. In this cohort study, obstetrical risk factors and perinatal outcome in 85 women exposed to CSA were compared to 170 matched unexposed women. CSA, physical abuse, and ACE were explored by face-to-face interviews and by questionnaire. Data on perinatal outcome were extracted from medical charts. Fisher's exact, χ2-test, and multiple logistic regression were used for statistical analysis. During pregnancy women with CSA experiences were significantly more often smoking (31.7%/9.4%; P<0.0001), had partners abusing drugs (10.6%/1.2%; P<0.0005), experienced physical (16.5%/0; P<0.0001), sexual (12.9%/0; P<0.0001), and emotional abuse (44.7%/1.7%; P<0.0001), reported depression (24.7%/1.8%; P<0.0001), and suicidal ideation (10.6%/0; P<0.0001) than women without CSA experiences. Differences in risk factors were more often correlated with physical than with sexual abuse during childhood. The probability for premature delivery was associated with CSA, physical abuse and ACE as well as with several of the risk factors investigated. Women with CSA, physical, and ACE present with a variety of abuse-associated obstetrical risk factors and an increased risk for premature delivery. Therefore, all types of abusive and other ACE should be considered in prenatal care.


Unraveling the Hexaploid Sweetpotato Inheritance Using Ultra-Dense Multilocus Mapping.
The hexaploid sweetpotato (Ipomoea batatas (L.) Lam., 2n = 6x = 90) is an important staple food crop worldwide and plays a vital role in alleviating famine in developing countries. Due to its high ploidy level, genetic studies in sweetpotato lag behind major diploid crops significantly. We built an ultra-dense multilocus integrated genetic map and characterized the inheritance system in a sweetpotato full-sib family using our newly developed software, MAPpoly. The resulting genetic map revealed 96.5% collinearity between I. batatas and its diploid relative I. trifida We computed the genotypic probabilities across the whole genome for all individuals in the mapping population and inferred their complete hexaploid haplotypes. We provide evidence that most of the meiotic configurations (73.3%) were resolved in bivalents, although a small portion of multivalent signatures (15.7%), among other inconclusive configurations (11.0%), were also observed. Except for low levels of preferential pairing in linkage group 2, we observed a hexasomic inheritance mechanism in all linkage groups. We propose that the hexasomic-bivalent inheritance promotes stability to the allelic transmission in sweetpotato.


Exercise with blood flow restriction: an updated evidence-based approach for enhanced muscular development.
A growing body of evidence supports the use of moderate blood flow restriction (BFR) combined with low-load resistance exercise to enhance hypertrophic and strength responses in skeletal muscle. Research also suggests that BFR during low-workload aerobic exercise can result in small but significant morphological and strength gains, and BFR alone may attenuate atrophy during periods of unloading. While BFR appears to be beneficial for both clinical and athletic cohorts, there is currently no common consensus amongst scientists and practitioners regarding the best practice for implementing BFR methods. If BFR is not employed appropriately, there is a risk of injury to the participant. It is also important to understand how variations in the cuff application can affect the physiological responses and subsequent adaptation to BFR training. The optimal way to manipulate acute exercise variables, such as exercise type, load, volume, inter-set rest periods and training frequency, must also be considered prior to designing a BFR training programme. The purpose of this review is to provide an evidence-based approach to implementing BFR exercise. These guidelines could be useful for practitioners using BFR training in either clinical or athletic settings, or for researchers in the design of future studies investigating BFR exercise.


Extreme ultraviolet observations from the voyager 2 encounter with saturn.
Combined analysis of helium (584 angstroms) airglow and the atmospheric occultations of the star delta Scorpii imply a vertical mixing parameter in Saturn's upper atmosphere of K (eddy diffusion coefficient) approximately 8 x 10(7) square centimeters per second, an order of magnitude more vigorous than mixing in Jupiter's upper atmosphere. Atmospheric H(2) band absorption of starlight yields a preliminary temperature of 400 K in the exosphere and a temperature near the homopause of approximately 200 K. The energy source for the mid-latitude H(2) band emission still remains a puzzle. Certain auroral emissions can be fully explained in terms of electron impact on H(2), and auroral morphology suggests a link between the aurora and the Saturn kilometric radiation. Absolute optical depths have been determined for the entire C ring andparts of the A and B rings. A new eccentric ringlet has been detected in the C ring. The extreme ultraviolet reflectance of the rings is fairly uniform at 3.5 to 5 percent. Collisions may control the distribution of H in Titan's H torus, which has a total vertical extent of approximately 14 Saturn radii normal to the orbit plane.


Use of acceptable daily intake (ADI) as a health-based benchmark in nutrition research studies that consider the safety of low-calorie sweeteners (LCS): a systematic map.
It is well-recognized that consumers face many challenges in understanding and applying nutritional guidance for low-calorie sweeteners (LCS). Thus, this research aims to (1) assess how benchmarks for safe levels of consumption of LCS are utilized by researchers, and (2) understand how varying use of such benchmarks may contribute to challenges in understanding and applying nutritional guidance for LCS consumption. A systematic mapping exercise was employed to characterize when and how acceptable daily intake (ADI) values are used as health-based benchmarks in nutrition research studies that consider the safety of LCS. Based on results from charting 121 studies, our findings demonstrate that comparisons of LCS intake to an ADI derived by an authoritative body have been made in a diverse set of published literature, varying widely in their objectives, approaches, and populations of interest. The majority of studies compared the ADI to intake in a population under study; these represent the type of comparison that is most consistent with the intent of the ADI. Other applications of the ADI included use as a benchmark in experimental studies, risk-benefit analyses, and metabolism studies. Although most instances of ADI use were reasonable within the context of the individual studies' objectives, the diversity in use by original-study authors amplifies the continued need for development of "best practices" regarding the use and interpretation of the ADIs in current research. Using comparisons to the ADI can be a helpful way to provide context to research findings. However, in doing so, it is important that researchers utilize the value in a manner specific with its intent, as the ADI is a metric that represents an estimate of the amount of a substance that can be consumed daily over a lifetime without presenting an appreciable risk to health.


Can Medical Students Evaluate Medical Websites?: A mixed-methods study from Oman.
This study aimed to discover the extent to which medical students can evaluate medical websites, evaluation criteria used, factors affecting their abilities and whether a teaching intervention could rectify problems. Medical students and practitioners are required to evaluate medical information available on the Internet. Most current medical students are familiar with the Internet, but their ability to evaluate material may require improvement. A class of undergraduate medical students evaluated an unreliable medical website, received a teaching intervention on website evaluation criteria and re-evaluated the same site. This mixed-methods study was conducted at Sultan Qaboos University, Muscat, Oman, from September to December 2018. A total of 149 (response rate: 82.3%) students participated. Students spent, on average, 4.69 hours per day on the Internet. No significant correlations were found between demographic indicators and Internet time. On a 10-point Likert scale, students' scores ranged from 5-6, with no significant differences between the pre- and post-intervention evaluations, except for increased polarisation away from the mean. Qualitative comments indicated an awareness of relevant criteria but an overall inability to critically apply them. The results indicate that one cannot make a blanket statement about medical students' ability to evaluate medical websites despite their familiarity with technology. Moreover, website evaluation should be viewed primarily from the information perspective and that critical thinking ability may play a major role. Due to these overriding factors, short interventions are unlikely to have an impact, and other educational strategies should be developed. These are necessary to ensure that medical students can function independently as life-long learners and medical professionals.


[The potential of three-dimensional tumor models and cell culturing in cancer research and diagnostics].
In vitro testing of antitumor agents on human cancer cell lines has become essential in pharmaceutical research and in clinical practice. Although the most widely used technique is the two-dimensional cell growing protocol (in tissue culture plates), the new three-dimensional methods are becoming more and more popular as their structure and complexity is more similar to the microenvironment of the real tumor. The aim of the present study is to describe the most widely used in vitro three-dimensional tumor models and to compare a RAFT(TM) three dimensional in vitro tumor model with the traditional two-dimensional tumor cell cultures. In the study, the viability and the enzyme activity of cultured A549 non-small cell lung cancer (NSCLC) cells under different conditions were compared. The results show that while the number of necrotic cells increased significantly (20-fold; 2D/A549 T75 conventional tissue culture flask 1.6%; 2D/A549-collagen coated T75 tissue culture flask 1.45%, RAFT(TM) 22.11%) during long culturing period in the RAFT(TM) three-dimensional in vitro tumor model, there was no significant difference during the conventional antitumor screening period (3-5 day) compared to the traditional two-dimensional cell cultures. The structure of the tumor cell islets grown with RAFT(TM) is much more complex than that of the traditional two-dimensional cultures. Thus, similarly to the in vivo tumor microenvironment, there is also a collagen matrix in the extracellular space which can have significant effect on the diffusion of the antitumor agents to cells. In conclusion, it can be stated that testing of antitumor agents on tumor cells cultured in three-dimensional systems can be an important complementary method to the traditional two-dimensional in vitro analyses. The results of the new three-dimensional method can be more easily applied in the in vivo analysis and translated into clinical practice.


Effects of Somatostatin Analogs and Dopamine Agonists on Insulin-Like Growth Factor 2-Induced Insulin Receptor Isoform A Activation by Gastroenteropancreatic Neuroendocrine Tumor Cells.
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) express insulin-like growth factor (IGF)-related factors [IGF1, IGF2; insulin receptor (IR)-A, IR-B; IGF-binding protein (IGFBP) 1-3] as well as somatostatin (SSTRs) and dopamine D2 receptors (D2Rs). To (1) compare mRNA expression of IGF-related factors in human pancreatic NET (panNET) cell lines with that in human GEP-NETs to evaluate the usefulness of these cells as a model for studying the IGF system in GEP-NETs, (2) determine whether panNET cells produce growth factors that activate IR-A, and (3) investigate whether somatostatin analogs (SSAs) and/or dopamine agonists (DAs) influence the production of these growth factors. In panNET cells (BON-1 and QGP-1) and GEP-NETs, mRNA expression of IGF-related factors was measured by quantitative real-time PCR. Effects of the SSAs octreotide and pasireotide (PAS), the DA cabergoline (CAB), and the dopastatin BIM-23A760 (all 100 nM) were evaluated at the IGF2 mRNA and protein level (by ELISA) and regarding IR-A bioactivity (by kinase receptor activation assay) in panNET cells. panNET cells and GEP-NETs had comparable expression profiles of IGF-related factors. Especially in BON-1 cells, IGF2 and IR-A were most highly expressed. PAS + CAB inhibited IGF2 (-29.5 ± 4.9%, p < 0.01) and IGFBP3 (-20.0 ± 4.0%, p < 0.01) mRNA expression in BON-1 cells. In BON-1 cells, IGF2 protein secretion was significantly inhibited with BIM-23A760 (-23.7 ± 3.8%). BON-1- but not QGP-1- conditioned medium stimulated IR-A bioactivity. In BON-1 cells, IR-A bioactivity was inhibited by BIM-23A760 and PAS + CAB (-37.8 ± 2.1% and -30.9 ± 4.1%, respectively, p < 0.0001). (1) The BON-1 cell line is a representative model for studying the IGF system in GEP-NETs, (2) BON-1 cells produce growth factors (IGF2) activating IR-A, and (3) combined SSTR and D2R targeting with PAS + CAB and BIM-23A760 suppresses IGF2-induced IR-A activation.


Comparison of laser surface scanning and fiducial marker-based registration in frameless stereotaxy. Technical note.
The authors compared the accuracy of laser surface scanning patient registration using the commercially available Fazer (Medtronic, Inc.) with the conventional registration procedure based on fiducial markers (FMs) in computer-assisted surgery. Four anatomical head specimens were prepared with 10 titanium microscrews placed at defined locations and scanned with a 16-slice spiral computed tomography unit. To compare the two registration methods, each method was applied five times for each cadaveric specimen; thus data were obtained from 40 registrations. Five microscrews (selected following a randomization protocol) were used for each FM-based registration; the other five FMs were selected for coordinate measurements by touching with a point measurement stylus. Coordinates of these points were also measured manually on the screen of the navigation computer. Coordinates were measured in the same manner after laser surface registration. The root mean square error as calculated by the navigation system ranged from 1.3 to 3.2 mm (mean 1.8 mm) with the Fazer and from 0.3 to 1.8 mm (mean 1.0 mm) with FM-based registration. The overall mean deviations (the arithmetic mean of the mean deviations of measurements on the four specimens) were 3.0 mm (standard deviation [SD] range 1.4-2.6 mm) with the Fazer and 1.4 mm (SD range 0.4-0.9 mm) with the FMs. The Fazer registration scans 300 surface points. Statistical tests showed the difference in the accuracy of these methods to be highly significant. In accordance with the findings of other groups, the authors concluded that the inclusion of a larger number of registration points might improve the accuracy of Fazer registration.


Chromosome condensation induced by geminivirus infection of mature plant cells.
Tomato golden mosaic virus (TGMV) is a geminivirus that replicates its single-stranded DNA genome through double-stranded DNA intermediates in nuclei of differentiated plant cells using host replication machinery. We analyzed the distribution of viral and plant DNA in nuclei of infected leaves using fluorescence in situ hybridization (FISH). TGMV-infected nuclei showed up to a sixfold increase in total volume and displayed a variety of viral DNA accumulation patterns. The most striking viral DNA patterns were bright, discrete intranuclear compartments, but diffuse nuclear localization was also observed. Quantitative and spatial measurements of high resolution 3-dimensional image data revealed that these compartments accounted for 1-18% of the total nuclear volume or 2-45% of the total nuclear FISH signals. In contrast, plant DNA was concentrated around the nuclear periphery. In a significant number of nuclei, the peripheral chromatin was organized as condensed prophase-like fibers. A combination of FISH analysis and indirect immunofluorescence with viral coat protein antibodies revealed that TGMV virions are associated with the viral DNA compartments. However, the coat protein antibodies failed to cross react with some large viral DNA inclusions, suggesting that encapsidation may occur after significant viral DNA accumulation. Infection by a TGMV mutant with a defective coat protein open reading frame resulted in fewer and smaller viral DNA-containing compartments. Nevertheless, nuclei infected with the mutant virus increased in size and in some cases showed chromosome condensation. Together, these results established that geminivirus infection alters nuclear architecture and can induce plant chromatin condensation characteristic of cells arrested in early mitosis.


Staphylococcus aureus sarA regulates inflammation and colonization during central nervous system biofilm formation.
Infection is a frequent and serious complication following the treatment of hydrocephalus with CSF shunts, with limited therapeutic options because of biofilm formation along the catheter surface. Here we evaluated the possibility that the sarA regulatory locus engenders S. aureus more resistant to immune recognition in the central nervous system (CNS) based on its reported ability to regulate biofilm formation. We utilized our established model of CNS catheter-associated infection, similar to CSF shunt infections seen in humans, to compare the kinetics of bacterial titers, cytokine production and inflammatory cell influx elicited by wild type S. aureus versus an isogenic sarA mutant. The sarA mutant was more rapidly cleared from infected catheters compared to its isogenic wild type strain. Consistent with this finding, several pro-inflammatory cytokines and chemokines, including IL-17, CXCL1, and IL-1β were significantly increased in the brain following infection with the sarA mutant versus wild type S. aureus, in agreement with the fact that the sarA mutant displayed impaired biofilm growth and favored a planktonic state. Neutrophil influx into the infected hemisphere was also increased in the animals infected with the sarA mutant compared to wild type bacteria. These changes were not attributable to extracellular protease activity, which is increased in the context of SarA mutation, since similar responses were observed between sarA and a sarA/protease mutant. Overall, these results demonstrate that sarA plays an important role in attenuating the inflammatory response during staphylococcal biofilm infection in the CNS via a mechanism that remains to be determined.


Use of a novel serum ELISA method and the tonsil-carrier state for evaluation of Mycoplasma hyosynoviae distributions in pig herds with or without clinical arthritis.
A novel indirect ELISA test using deoxycholate extracted antigens coated onto a hydrophobic polystyrene surface for measurement of serum antibodies specific for Mycoplasma hyosynoviae was developed. Sensitivity and specificity of the test were found to be superior to previous ELISAs as tested on porcine serum following experimental Mycoplasma infections as well as by analysis of samples from one Danish herd known to be free of M. hyosynoviae and samples from two Norwegian herds without clinical suspicion of M. hyosynoviae infections since their establishment. The epidemiology of M. hyosynoviae infection was then investigated in Danish pig herds with evidence of clinical M. hyosynoviae arthritis (MhA herds, n = 4) and in herds with M. hyosynoviae-carriers among slaughter pigs, but with limited clinical lameness (MhC herds, n = 4). M. hyosynoviae bacteriaemia and tonsil-carrier state were determined by culture of cross-sectional samples of whole-blood (n = 238) and tonsil scrapings (n = 322), respectively. Levels of serum antibodies (n = 396) were measured by the novel indirect ELISA test. There was no significant difference in the ELISA results between the MhA and the MhC herds. Pigs that were tonsil-carriers had a significantly higher response in the ELISA test (P < 0.001) than non-carriers. Slaughter pigs showed higher ELISA values (P < 0.001) and they were more prone to be tonsil-carriers (P < 0.001). The most critical period for spread of the infection seems to be the nursery period (4-12 weeks). The results indicate that M. hyosynoviae infection progresses similarly in herds irrespective of the presence of clinical arthritis. Thus, clinical arthritis due to M. hyosynoviae is probably triggered by other host or herd factors than low levels of serum antibodies or by differences in virulence factors between M. hyosynoviae strains.


Alternating Copolymer of Double Four Ring Silicate and Dimethyl Silicone Monomer-PSS-1.
A new copolymer consisting of double four ring (D4R) silicate units linked by dimethylsilicone monomer referred to as polyoligosiloxysilicone number one (PSS-1) was synthesized. The D4R building unit is provided by hexamethyleneimine cyclosilicate hydrate crystals, which were dehydrated and reacted with dichlorodimethylsilane. The local structure of D4R silicate units and dimethyl silicone monomers was revealed by multidimensional solid-state NMR, FTIR and modeling. On average, D4R silicate units have 6.8 silicone linkages. Evidence for preferential unidirectional growth and chain ordering within the PSS-1 copolymer was provided by STEM and TEM. The structure of PSS-1 copolymer consists of twisted columns of D4R silicate units with or without cross-linking. Both models are consistent with the spectroscopic, microscopic and physical properties. PSS-1 chains are predicted to be mechanically strong compared to silicones such as PDMS, yet more flexible than rigid silica materials such as zeolites.


Mother's Emotional and Posttraumatic Reactions after a Preterm Birth: The Mother-Infant Interaction Is at Stake 12 Months after Birth.
Very preterm infants are known to be at risk of developmental disabilities and behavioural disorders. This condition is supposed to alter mother-infant interactions. Here we hypothesize that the parental coping with the very preterm birth may greatly influence mother-infant interactions. 100 dyads were included in 3 university hospitals in France. Preterm babies at higher risk of neurodevelopmental sequelae (PRI>10) were excluded to target the maternal determinants of mother-infant interaction. We report the follow-up of this cohort during 1 year after very preterm birth, with regular assessment of infant somatic state, mother psychological state and the assessment of mother-infant interaction at 12 months by validated scales (mPPQ, HADS, EPDS, PRI, DDST and PIPE). We show that the intensity of post-traumatic reaction of the mother 6 months after birth is negatively correlated with the quality of mother-infant interaction at 12 months. Moreover, the anxious and depressive symptoms of the mother 6 and 12 months after birth are also correlated with the quality of mother-infant interaction at 12 months. By contrast, this interaction is not influenced by the initial affective state of the mother in the 2 weeks following birth. In this particular population of infants at low risk of sequelae, we also show that the quality of mother-infant interaction is not correlated with the assessment of the infant in the neonatal period but is correlated with the fine motor skills of the baby 12 months after birth. This study suggests that mothers' psychological condition has to be monitored during the first year of very preterm infants' follow-up. It also suggests that parental interventions have to be proposed when a post-traumatic, anxious or depressive reaction is suspected.


Hepatoprotective effects of zataria multiflora ethanolic extract on liver toxicity induced by cyclophosphamide in mice.
Although cyclophosphamide (CP), an alkylating agent, has been extensively used in chemotherapy, it possesses a wide spectrum of adverse effects including hepatotoxicity. This study was aimed to evaluate the protective effects of Zataria multiflora against hepatic damage induced by CP in mice.Mice were orally (gavages) pretreated with the ethanolic extract aerial parts of Zataria at doses of 50, 100, 200, or 400 mg/kg for 7 consecutive days before a single intraperitoneal injection of 200 mg/kg CP. After 24 h, animals were anesthetized, blood samples and hepatic tissues were collected and used for biochemical and histological examination.Serum levels of hepatic markers were significantly increased after only CP treated animals but restored in Zataria pretreated groups. A single dose of CP administration also markedly induced abnormality in the levels of several biomarkers associated with oxidative stress in liver tissues homogenates. However, pretreatment with Zataria significantly inhibited the abnormality of antioxidant enzymes defense system in the liver tissues. In addition, histopathological studies proved that CP causes damage to the liver, and this was evidenced by the induced dilated and congested sinusoidal space, lymphocytic infiltration between hepatocytes, portal space with moderate to severe inflammation and necrotic hepatocyte with absence of nuclei. Zataria effectively protected animals against CP-induced hepatic tissue damages.Our results reveal that Zataria produces a potent hepatoprotective role and could be a potent candidate to use concomitantly as a supplement agent against hepatotoxicity of CP for the patients undergoing chemotherapy.


Aflatoxin-free transgenic maize using host-induced gene silencing.
Aflatoxins, toxic secondary metabolites produced by some Aspergillus species, are a universal agricultural economic problem and a critical health issue. Despite decades of control efforts, aflatoxin contamination is responsible for a global loss of millions of tons of crops each year. We show that host-induced gene silencing is an effective method for eliminating this toxin in transgenic maize. We transformed maize plants with a kernel-specific RNA interference (RNAi) gene cassette targeting the aflC gene, which encodes an enzyme in the Aspergillus aflatoxin biosynthetic pathway. After pathogen infection, aflatoxin could not be detected in kernels from these RNAi transgenic maize plants, while toxin loads reached thousands of parts per billion in nontransgenic control kernels. A comparison of transcripts in developing aflatoxin-free transgenic kernels with those from nontransgenic kernels showed no significant differences between these two groups. These results demonstrate that small interfering RNA molecules can be used to silence aflatoxin biosynthesis in maize, providing an attractive and precise engineering strategy that could also be extended to other crops to improve food security.


Do antidepressants increase the risk of mania and bipolar disorder in people with depression? A retrospective electronic case register cohort study.
To investigate the association between antidepressant therapy and the later onset of mania/bipolar disorder. Retrospective cohort study using an anonymised electronic health record case register. South London and Maudsley National Health Service (NHS) Trust (SLaM), a large provider of inpatient and community mental healthcare in the UK. 21,012 adults presenting to SLaM between 1 April 2006 and 31 March 2013 with unipolar depression. Prior antidepressant therapy recorded in electronic health records. Time to subsequent diagnosis of mania or bipolar disorder from date of diagnosis of unipolar depression, censored at 31 March 2014. Multivariable Cox regression analysis with age and gender as covariates. The overall incidence rate of mania/bipolar disorder was 10.9 per 1000 person-years. The peak incidence of mania/bipolar disorder incidence was seen in patients aged between 26 and 35 years (12.3 per 1000 person-years). Prior antidepressant treatment was associated with an increased incidence of mania/bipolar disorder ranging from 13.1 to 19.1 per 1000 person-years. Multivariable analysis indicated a significant association with selective serotonin reuptake inhibitors (HR 1.34, 95% CI 1.18 to 1.52) and venlafaxine (1.35, 1.07 to 1.70). In people with unipolar depression, antidepressant treatment is associated with an increased risk of subsequent mania/bipolar disorder. These findings highlight the importance of considering risk factors for mania when treating people with depression.


A Computational Framework for Electrical Stimulation of Vestibular Nerve.
The vestibular organs are very important to generate reflexes critical for stabilizing gaze and body posture. Vestibular diseases significantly reduce the quality of life of people who are affected by them. Some research groups have recently started developing vestibular neuroprostheses to mitigate these symptoms. However, many scientific and technological issues need to be addressed to optimise their use in clinical trials. We developed a computational model able to mimic the response of human vestibular nerves and which can be exploited for "in-silico" testing of new strategies to design implantable vestibular prostheses. First, a digital model of the vestibular system was reconstructed from anatomical data. Monopolar stimulation was delivered at different positions and distances from ampullary nerves. The electrical potential induced by the injected current was computed through finite-element methods and drove extra-cellular stimulation of fibers in the vestibular, facial, and cochlear nerves. The electrical activity of vestibular nerves and the resulting eye movements elicited by different stimulation protocols were investigated. A set of electrode configurations was analyzed in terms of selectivity at increasing injected current. Electrode position along the nerve plays a major role in producing undesired activity in other nontargeted nerves, whereas distance from the fiber does not significantly affect selectivity. Indications are provided to minimize misalignment in nonoptimal electrode locations. Eye movements elicited by the different stimulation protocols are calculated and compared to experimental values, for the purpose of model validation.


Development and confirmatory factor analysis of the community norms of child neglect scale.
This article describes the development of the Community Norms of Child Neglect Scale (CNCNS), a new measure of perceptions of child neglect, for use in community samples. The CNCNS differentiates among four subtypes of neglect (failure to provide for basic needs, lack of supervision, emotional neglect, and educational neglect). Scenarios ranging in seriousness for each subtype were presented to a large community sample (N = 3,809). Confirmatory factor analyses indicated that a four-factor model provided a better fit to the data than did a model specifying only one overall neglect factor, suggesting this sample distinguished among the four subtypes of neglect. The authors tested measurement equivalence across individuals who work with children and lay community respondents and across rural and urban respondents, with results indicating a very similar structure across these groups. These initial reliability and validity data suggest that the CNCNS may be of use in comparing perceptions of child neglect among individuals and across communities.


End-to-end lung cancer screening with three-dimensional deep learning on low-dose chest computed tomography.
With an estimated 160,000 deaths in 2018, lung cancer is the most common cause of cancer death in the United States1. Lung cancer screening using low-dose computed tomography has been shown to reduce mortality by 20-43% and is now included in US screening guidelines1-6. Existing challenges include inter-grader variability and high false-positive and false-negative rates7-10. We propose a deep learning algorithm that uses a patient's current and prior computed tomography volumes to predict the risk of lung cancer. Our model achieves a state-of-the-art performance (94.4% area under the curve) on 6,716 National Lung Cancer Screening Trial cases, and performs similarly on an independent clinical validation set of 1,139 cases. We conducted two reader studies. When prior computed tomography imaging was not available, our model outperformed all six radiologists with absolute reductions of 11% in false positives and 5% in false negatives. Where prior computed tomography imaging was available, the model performance was on-par with the same radiologists. This creates an opportunity to optimize the screening process via computer assistance and automation. While the vast majority of patients remain unscreened, we show the potential for deep learning models to increase the accuracy, consistency and adoption of lung cancer screening worldwide.


Differential cognitive and behavioral effects of carbamazepine and lamotrigine.
The relative cognitive and behavioral effects of lamotrigine compared with the older standard antiepileptic drugs (AED) are uncertain. To directly compare the cognitive and behavioral effects of carbamazepine and lamotrigine. The cognitive and behavioral effects of carbamazepine and lamotrigine were assessed in 25 healthy adults using a double-blind, randomized crossover design with two 10-week treatment periods. During each treatment condition, subjects received either lamotrigine (150 mg/day) or carbamazepine (mean 696 mg/day) adjusted to a dose to achieve midrange standard therapeutic blood levels (mean 7.6 microg/mL). Subjects were tested at the end of each AED treatment period and in three drug-free conditions (two pretreatment baselines and a final posttreatment period [1 month after last AED]). The neuropsychological test battery included 19 measures yielding 40 total variables. Direct comparison of the two AED revealed significantly better performance on 19 (48%) variables for lamotrigine but none for carbamazepine. Differences spanned both objective cognitive and subjective behavioral measures, including cognitive speed, memory, graphomotor coding, neurotoxic symptoms, mood factors, sedation, perception of cognitive performance, and other quality-of-life perceptions. Comparison of carbamazepine with the nondrug average revealed significantly better performance for nondrug average on 24 (62%) variables but none for carbamazepine. Comparison of lamotrigine with nondrug average revealed better performance on one (2.5%) variable for nondrug average and on one (2.5%) variable for lamotrigine. Lamotrigine produces significantly fewer untoward cognitive and behavioral effects than carbamazepine at the dosages used in this study.


Obesity, sleep apnea, and hypertension.
Obesity has a high and rising prevalence and represents a major public health problem. Obstructive sleep apnea (OSA) is also common, affecting an estimated 15 million Americans, with a prevalence that is probably also rising as a consequence of increasing obesity. Epidemiologic data support a link between obesity and hypertension as well as between OSA and hypertension. For example, untreated OSA predisposes to an increased risk of new hypertension, and treatment of OSA lowers blood pressure, even during the daytime. Possible mechanisms whereby OSA may contribute to hypertension in obese individuals include sympathetic activation, hyperleptinemia, insulin resistance, elevated angiotensin II and aldosterone levels, oxidative and inflammatory stress, endothelial dysfunction, impaired baroreflex function, and perhaps by effects on renal function. The coexistence of OSA and obesity may have more widespread implications for cardiovascular control and dysfunction in obese individuals and may contribute to some of the clustering of abnormalities broadly defined as the metabolic syndrome. From the clinical and therapeutic perspectives, the presence of resistant hypertension and the absence of a nocturnal decrease in blood pressure in obese individuals should prompt the clinician to consider the diagnosis of OSA, especially if clinical symptoms suggestive of OSA (such as poor sleep quality, witnessed apnea, excessive daytime somnolence, and so forth) are also present.


The role of patient navigators in eliminating health disparities.
Despite many important efforts to increase equity in the US health care system, not all Americans have equal access to health care-or similar health outcomes. With the goal of lowering costs and increasing accessibility to health care, the nation's new health care reform legislation includes certain provisions that expand health insurance coverage to uninsured and underinsured populations, promote medical homes, and support coordination of care. These provisions may help narrow existing health care disparities. Many of the most vulnerable patients, however, may continue to have difficulty accessing and navigating the complex US health care delivery system. This article explores the unique role that patient navigation can play in improving health outcomes for racial and ethnic minorities, as well as other underserved populations, in the context of a changing healthcare environment. Patient navigators can not only facilitate improved health care access and quality for underserved populations through advocacy and care coordination, but they can also address deep-rooted issues related to distrust in providers and the health system that often lead to avoidance of health problems and non-compliance with treatment recommendations. By addressing many of the disparities associated with language and cultural differences and barriers, patient navigators can foster trust and empowerment within the communities they serve. Specific patient navigator activities are discussed, and metrics to evaluate program efforts are presented.


Comparing two methods for deriving dietary patterns associated with risk of metabolic syndrome among middle-aged and elderly Taiwanese adults with impaired kidney function.
Dietary patterns were associated with the risk of chronic disease development and outcome-related diseases. In this study, we aimed to compare the correlation between dietary patterns and metabolic syndrome (MetS) using two methods for identifying dietary patterns. The participants (n = 25,569) aged ≥40 years with impaired kidney function were retrieved from Mei Jau (MJ) Health Screening database from 2008 to 2010. Dietary patterns were identified by principal component analysis (PCA) and reduced rank regression (RRR) from twenty-two food groups using PROC FACTOR and PROC PLS functions. We identified two similar dietary pattern characteristics (high intakes of deep fried foods, preserved or processed foods, dipping sauce, meat, sugary drinks, organ meats, jam/honey, fried rice/flour products, instant noodles and eggs) derived by PCA and RRR. Logistic regression analysis revealed that RRR-derived dietary pattern scores were positively associated with an odds ratio (OR = 1.70, 95% CI: 1.56, 1.86) of having MetS than PCA-derived dietary pattern scores (OR = 1.38, 95% CI: 1.27, 1.51). The correlations between RRR-derived dietary pattern scores and elevated systolic and diastolic blood pressure (OR = 1.30 for both) or low high density lipoprotein cholesterol in women (OR = 1.32) were statistically significant but not significant in PCA-derived dietary pattern scores. Our findings suggest that RRR gives better results when studying behavior related dietary patterns in association with MetS. RRR may be more preferable to provide dietary information for developing dietary guidelines among people with MetS. Further studies with prospective measurements are needed to verify whether RRR is a useful analytic tool for the association between dietary patterns and other chronic diseases.


In vitro and in vivo characterization of two nonsporulating Aspergillus fumigatus clinical isolates from immunocompetent patients.
Aspergillus fumigatus is a pathogenic fungus responsible for invasive aspergillosis (IA). Typically, it can produce abundant conidia to survive and spread. The infection by A. fumigatus usually occurs in immunocompromised patients due to failed clearance of inhaled conidia. However, the incidence of aspergillosis in immunocompetent hosts has been increasing, the pathogenesis of which is still unknown. Our team previously obtained two clinical nonsporulating A. fumigatus isolates from non-immunocompromised patients, which only have the form of hyphae. This present study demonstrated the in vitro and in vivo characteristics of the two nonsporulating A. fumigatus isolates and verified that their conidiation defects are associated to abolished expression of the sporulation-related central regulatory pathway brlA gene. In addition, we confirmed the mutation site of brlA gene (c.657_660delTCCT) contributes to the nonsporulating phenotype in one clinical isolate. Plate assay showed that the two nonsporulating isolates have a similar resistance to antifungal drugs, cell wall disturbing substances, and oxidative stress compared with the wild-type reference Af293. Most important of all, we employed an immunocompetent mouse model to mimic the pathogenesis of pulmonary aspergillosis in non-immunocompromised patients. It revealed that the hyphae of two nonsporulating isolates and Af293 have similar virulence in immunocompetent hosts. Interestingly, the hyphae fragments of Af293 but not conidia are able to induce invasive aspergillosis in immunocompetent mice. In conclusion, our study indicate that the form of hyphae may play a dominant causative role in pulmonary aspergillosis of immunocompetent hosts rather than conidia.


Shear-Wave Elastography in the Characterization of Pleural Effusions.
The aim of the study was to investigate the efficacy of shear-wave elastography (SWE) in the differentiation of transudative and exudative pleural effusions. This monocentric study comprised 60 cases (17 transudative, 43 exudative).Transthoracic SWE was performed in 60 cases for whom to use thoracentesis for the pleural fluid analysis was planned. The mean SWE values of each patient were recorded, and the correlation between the biochemical analysis results of pleural fluid after thoracentesis and SWE findings was evaluated. The effusion SWE values and biochemical analysis results were compared. Of the 60 patients who participated in this study, 32 (53.4) were male and 28 (46.6%) were female. The mean ± SD age was 59 ± 17.09 years (range = 21-89 years). Simultaneous serum biochemical analysis was performed for the patients with PE. The mean ± SD shear-wave velocity value of the transudative fluid was calculated 2.29 ± 0.41 (1.6-2.94), whereas the mean ± SD shear-wave velocity value of the exudative pleural fluid was calculated as 3.29 ± 0.63 (2.01-4.88) (P < 0.001). The receiver operating characteristic analysis showed that sensitivity and specificity were found as 91% and 76.5%, respectively, when the cutoff value was selected as 2.52 m/s in the differentiation of the transudative and exudative effusions.Shear-wave elastography may help in the differentiation of transudative and exudative of the pleural effusions.


Telomerase mediates vascular endothelial growth factor-dependent responsiveness in a rat model of hind limb ischemia.
Telomere dysfunction contributes to reduced cell viability, altered differentiation, and impaired regenerative/proliferative responses. Recent advances indicate that telomerase activity confers a pro-angiogenic phenotype to endothelial cells and their precursors. We have investigated whether telomerase contributes to tissue regeneration following hind limb ischemia and vascular endothelial growth factor 165 (VEGF(165)) treatment. VEGF delivery induced angiogenesis and increased expression of the telomerase reverse transcriptase (TERT) and telomerase activity in skeletal muscles and satellite and endothelial cells. Adenovirus-mediated transfer of wild type TERT but not of a dominant negative mutant, TERTdn, significantly induced capillary but not arteriole formation. However, when co-delivered with VEGF, TERTdn abrogated VEGF-dependent angiogenesis, arteriogenesis, and blood flow increase. This effect was paralleled by in vitro evidence that telomerase inhibition by 3'-azido-3'-deoxythymidine in VEGF-treated endothelial cells strongly reduced capillary density and promoted apoptosis in the absence of serum. Similar results were obtained with adenovirus-mediated expression of TERTdn and AKTdn, both reducing endogenous TERT activity and angiogenesis on Matrigel. Mechanistically, neo-angiogenesis in our system involved: (i) VEGF-dependent activation of telomerase through the nitric oxide pathway and (ii) telomerase-dependent activation of endothelial cell differentiation and protection from apoptosis. Furthermore, detection of TERT in activated satellite cells identified them as VEGF targets during muscle regeneration. Because TERT behaves as an angiogenic factor and a downstream effector of VEGF signaling, telomerase activity appears required for VEGF-dependent remodeling of ischemic tissue at the capillaries and arterioles level.


The pig tapeworm Taenia solium, the cause of cysticercosis: Biogeographic (temporal and spacial) origins in Madagascar.
Cysticercosis is a serious public health problem in Madagascar. The prevalence rate of active cysticercosis reached 21% in regions with a high level of livestock farming. Taenia solium of African-American and Asian genotypes are both present on the island. The times of divergence of the 13 specimens studied suggests a very ancient diversification of T. solium. These events are widely thought to be prior to the domestication of pigs, and seem to follow the expansion of Homo in Asia. Multiple human migrations and the diversity of potential intermediate hosts may have led to a complex epidemiological situation on the island.


Computerized weight loss intervention optimizes staff time: the clinical and cost results of a controlled clinical trial conducted in a managed care setting.
To evaluate the costs and effects of incremental components of a weight-loss program. A 3-arm, 12-month randomized controlled clinical trial to evaluate 3 incremental levels of intervention intensity. The study included 588 individuals (BMI > 25 kg/m2) in a freestanding health maintenance organizalion and achieved an 81% completion rate. Using a cognitive behavioral approach for tailoring lifestyle modification goals, the incremental levels of intervention included a) a workbook alone, b) the addition of computerized tailoring using onsite computer kiosks with touch screen monitors, and c) the addition of both computers and staff consultation. Endpoints included weight parameters, lipid profile, plasma glucose, blood pressure, intervention costs, dietary intake, and physical activity. Study endpoints were analyzed using analysis of variance for normally distributed variables and analysis of covariance to control for any baseline differences. Regression and correlation analysis assessed the relationship between weight loss and other variables. For the increasing levels of intervention intensity, the mean 12-month weight losses were 2.2, 4.7, and 7.4 pounds, with the respective cost per participant being $12.33, $41.99, and $133.74. The decreases in mean BMIs for these respective intervelation levels were 0.4, 0.9 and 1.2. All groups reported a decrease in energy and fat intake and an increase in blocks walked (P<.01). Intervention variables that correlated with weight loss included more computer log-ons, achieving computer-selected goals, more self-monitoring, increased walking, and decreased energy and fat intake, as well as higher attendance in staff consultation group sessions for that treatment condition. Weight loss correlated with decreases in fasting glucose and blood pressure. In a weight-loss program, computers can facilitate selecting behavioral change goals. More frequent usage resulted in greater weight loss. Staff counseling to augment the computer intervention achieved the most weight loss.


Micro-UFO (Untethered Floating Object): A Highly Accurate Microrobot Manipulation Technique.
A new microrobot manipulation technique with high precision (nano level) positional accuracy to move in a liquid environment with diamagnetic levitation is presented. Untethered manipulation of microrobots by means of externally applied magnetic forces has been emerging as a promising field of research, particularly due to its potential for medical and biological applications. The purpose of the presented method is to eliminate friction force between the surface of the substrate and microrobot. In an effort to achieve high accuracy motion, required magnetic force for the levitation of the microrobot was determined by finite element method (FEM) simulations in COMSOL (version 5.3, COMSOL Inc., Stockholm, Sweden) and verified by experimental results. According to position of the lifter magnet, the levitation height of the microrobot in the liquid was found analytically, and compared with the experimental results head-to-head. The stable working range of the microrobot is between 30 µm to 330 µm, and it was confirmed in both simulations and experimental results. It can follow the given trajectory with high accuracy (<1 µm error avg.) at varied speeds and levitation heights. Due to the nano-level positioning accuracy, desired locomotion can be achieved in pre-specified trajectories (sinusoidal or circular). During its locomotion, phase difference between lifter magnet and carrier magnet has been observed, and relation with drag force effect has been discussed. Without using strong electromagnets or bulky permanent magnets, our manipulation approach can move the microrobot in three dimensions in a liquid environment.


Control of Neisseria gonorrhoeae pilin gene expression by environmental factors: involvement of the pilA/pilB regulatory genes.
The control of the expression of the pilin gene (pilE) in Neisseria gonorrhoeae under a wide variety of growth conditions has been studied. The expression of pilE was measured using transcriptional fusions between pilE and the gene encoding chloramphenicol acetyltransferase (CAT), and the level of pilin production was measured by Western blot analysis. Many of the conditions tested affected both growth rate and pilin gene expression (e.g. isoleucine, high osmolarity, high temperature, anaerobic growth, pH 6, urea and iron depletion). Changes in the level of many other proteins were also observed, depending on the conditions, indicating that gonococci undergo an adaptive response to environmental variations. Moreover, environment-induced changes in the level of many proteins, including pilin, seem to involve the pilA/pilB regulatory system, which has been previously proposed to modulate the expression of the gonococcal pilin gene.


Lignans and flavonoids inhibit aromatase enzyme in human preadipocytes.
Lignans and flavonoids are naturally-occurring diphenolic compounds found in high concentrations in whole grains, legumes, fruits and vegetables. Seven lignans and six flavonoids were evaluated for their abilities to inhibit aromatase enzyme activity in a human preadipose cell culture system. The lignan, enterolactone (Enl) and its theoretical precursors, 3'-demethoxy-3O-demethylmatairesinol (DMDM) and didemethoxymatairesinol (DDMM) decreased aromatase enzyme activity, with Ki values of 14.4, 5.0 and 7.3 microM, respectively. The flavonoids, coumestrol, luteolin and kaempferol also decreased aromatase enzyme activity, with Ki values of 1.3, 4.8 and 27.2 microM, respectively. Aminoglutethimide, a pharmaceutical aromatase inhibitor, showed a Ki value of 0.5 microM. Kinetic studies showed the inhibition by all compounds to be competitive. Smaller decreases in aromatase activity were observed with the lignan, enterodiol (End) and its theoretical precursors, O-demethylsecoisolariciresinol (ODSI), demethoxysecoisolariciresinol (DMSI) and didemethylsecoisolariciresinol (DDSI). The flavonoids, O-demethylangolensin (O-Dma), fisetin and morin showed no inhibitory effects. The inhibition of human preadipocyte aromatase activity by lignans and flavonoids suggests a mechanism by which consumption of lignan- and flavonoid-rich plant foods may contribute to reduction of estrogen-dependent disease, such as breast cancer.


The dynamics of resting fluctuations in the brain: metastability and its dynamical cortical core.
In the human brain, spontaneous activity during resting state consists of rapid transitions between functional network states over time but the underlying mechanisms are not understood. We use connectome based computational brain network modeling to reveal fundamental principles of how the human brain generates large-scale activity observable by noninvasive neuroimaging. We used structural and functional neuroimaging data to construct whole- brain models. With this novel approach, we reveal that the human brain during resting state operates at maximum metastability, i.e. in a state of maximum network switching. In addition, we investigate cortical heterogeneity across areas. Optimization of the spectral characteristics of each local brain region revealed the dynamical cortical core of the human brain, which is driving the activity of the rest of the whole brain. Brain network modelling goes beyond correlational neuroimaging analysis and reveals non-trivial network mechanisms underlying non-invasive observations. Our novel findings significantly pertain to the important role of computational connectomics in understanding principles of brain function.


Assessing the genetic risk for alcohol use disorders.
The past two decades have witnessed a revolution in the field of genetics which has led to a rapid evolution in the tools and techniques available for mapping genes that contribute to genetically complex disorders such as alcohol dependence. Research in humans and in animal models of human disease has provided important new information. Among the most commonly applied approaches used in human studies are family studies, case-control studies, and genome-wide association studies. Animal models have been aimed at identifying genetic regions or individual genes involved in different aspects of alcoholism, using such approaches as quantitative trait locus analysis, genome sequencing, knockout animals, and other sophisticated molecular genetic techniques. All of these approaches have led to the identification of several genes that seem to influence the risk for alcohol dependence, which are being further analyzed. Newer studies, however, also are attempting to look at the genetic basis of alcoholism at the level of the entire genome, moving beyond the study of individual genes toward analyses of gene interactions and gene networks in the development of this devastating disease.


Colorimetric and spectroradiometric characteristics of narrow-field-of-view clear skylight in Granada, Spain.
As part of our ongoing research into the clear daytime sky's visible structure, we analyze over 1,500 skylight spectra measured during a seven-month period in Granada, Spain. We use spectral radiances measured within 3 degrees fields of view (FOV's) to define colorimetric characteristics along four sky meridians: the solar meridian and three meridians at azimuths of 45 degrees, 90 degrees, and 315 degrees relative to it. The resulting clear-sky chromaticities in 44 different view directions (1) are close to but do not coincide with the CIE daylight locus, (2) form V-shaped meridional chromaticity curves along it (as expected from theory), and (3) have correlated color temperatures (CCT's) ranging from 3,800 K to infinity K. We also routinely observe that sky color and luminance are asymmetric about the solar meridian, usually perceptibly so. A principal-components analysis shows that three vectors are required for accurate clear-sky colorimetry, whereas six are needed for spectral analyses.