Heaviness of smoking index, number of cigarettes smoked and the Fagerstrom test for nicotine dependence among adult male Malaysians.
Two methods of identifying smokers with high nicotine dependence, the heaviness of smoking index (HSI) and number of cigarettes per day (CPD) were compared with the Fagerstrom test for nicotine dependence (FTND). The HSI, CPD and the FTND were administered to 316 adult Malaysian male, daily smokers aged between 25-64 years old in the Malaysian NCD Surveillance-1 Survey using a two-stage stratified random sampling of enumeration blocks and living quarters, via an interview based on a validated questionnaire. The cut-off point for classification of high nicotine dependence on the HSI was a score of four or higher, and for the heavy smoking category, smoking more than 20 cigarettes per day. Classification using each method was compared with classification by the FTND (score of six or more) as the reference standard. Sensitivity, specificity and kappa statistics for concordance between both measures and the FTND were evaluated. The HSI gave a similar prevalence rate of high nicotine dependence as the FTND. There was substantial agreement between the HSI and the FTND (kappa=0.63.), with moderate sensitivity (69.8%) and high specificity (92.5%). However, prevalence of high nicotine dependence using the CPD was 7% lower than the FTND. The heavy smoking category also showed fair agreement with the FTND (kappa=0.45) and moderate sensitivity (67.0%), but specificity was high (86.9%). The findings indicate that the HSI can be used as an alternative to the FTND in screening for high nicotine dependence among daily smokers in large population-based studies, while CPD may not be a suitable alternative to the FTND.


Targeting Impaired Antimicrobial Immunity in the Brain for the Treatment of Alzheimer's Disease.
Alzheimer's disease (AD) is the most common form of dementia and aging is the most common risk factor for developing the disease. The etiology of AD is not known but AD may be considered as a clinical syndrome with multiple causal pathways contributing to it. The amyloid cascade hypothesis, claiming that excess production or reduced clearance of amyloid-beta (Aβ) and its aggregation into amyloid plaques, was accepted for a long time as the main cause of AD. However, many studies showed that Aβ is a frequent consequence of many challenges/pathologic processes occurring in the brain for decades. A key factor, sustained by experimental data, is that low-grade infection leading to production and deposition of Aβ, which has antimicrobial activity, precedes the development of clinically apparent AD. This infection is chronic, low grade, largely clinically silent for decades because of a nearly efficient antimicrobial immune response in the brain. A chronic inflammatory state is induced that results in neurodegeneration. Interventions that appear to prevent, retard or mitigate the development of AD also appear to modify the disease. In this review, we conceptualize further that the changes in the brain antimicrobial immune response during aging and especially in AD sufferers serve as a foundation that could lead to improved treatment strategies for preventing or decreasing the progression of AD in a disease-modifying treatment.


The influence of experimentally induced copper deficiency on the fertility of rams. II. Macro- and microscopic changes in the testes.
The macro- and microscopic changes of the testes caused by molybdenum as well as a molybdenum plus sulphate induced copper deficiency were investigated in S.A. Mutton Merino rams. Judged on testes measurements, the testes development of rams suffering from a severe copper deficiency was slower (P less than or equal to 0.05) when compared with rams in the control group. Histological examinations of the testes of the rams which suffered from a severe copper deficiency revealed that the seminiferous tubules were less developed and less active than those of the control group. This was mainly due to the inactivity of the Sertoli cells. Where rams suffered from a copper deficiency, the Sertoli cells contained only a small volume of cytoplasm. The typical fingerlike cytoplasmic evaginations of the Sertoli cells into the lumen of the seminiferous tubules were absent while the nuclei of these cells were darkly stained, in some cases even pycnotic. Spermatocytogenesis was normal because primary spermatocytes with dark stained thread-like chromatin were observed in most of the seminiferous tubules. The process of spermiogenesis (metamorphic phase) did not take place. This can be accounted for by the inactivity of the Sertoli cells.


Outcomes of Resection and Joint-Preserving Arthroplasty for Forefoot Deformities for Rheumatoid Arthritis.
We investigated the clinical outcomes of resection and joint-preserving arthroplasty for forefoot deformities in patients with rheumatoid arthritis. Sixteen feet of 14 women (average age, 67.1 years; range, 53-82) underwent resection arthroplasty of the metatarsal head (resection group), and 18 feet of 15 women (average age, 61.3 years; range, 40-73) underwent a metatarsophalangeal joint-preserving procedure with shortening oblique metatarsal osteotomies of the lesser toes (joint preservation group). The mean disease duration in the resection and joint preservation groups was 23.6 and 19.1 years, and the average follow-up period was 37.3 and 33.5 months, respectively. The classification of Larsen was used to assess the severity of destruction of the metatarsophalangeal (MTP) joint. Preoperative and postoperative clinical evaluation included Japanese Society for Surgery of the Foot (JSSF) score and postoperative complications. The number of preoperative radiographic destruction of the MTP joints (Larsen grade II, III, IV, and V) was 0, 29, 39, and 12 joints in the resection group and 13, 67, 9, and 1 joints in the joint preservation group. The mean JSSF score improved significantly from 61.3 to 83.9 points in the resection group ( P < .001) and from 62.2 to 90.8 points in the joint preservation group ( P < .001). In the resection group, recurrence of callosities and claw toe deformity was observed in 6 and 3 feet, respectively. In the joint-preserving group, recurrence of callosities and hammer toe deformity was observed in 1 foot each. The resection arthroplasty and joint-preserving procedure showed satisfactory clinical outcomes. However, whether both procedures can maintain the good clinical results without the recurrence of forefoot deformity will require longer follow-up. Level III, retrospective comparative series.


The optimization of microwave digestion procedures and application to an evaluation of potentially toxic element contamination on a former industrial site.
The optimization of a microwave dissolution procedure for potentially toxic elements in a contaminated soil sample has been evaluated using a central composite design approach. By considering the operating parameters of temperature, digestion time, microwave power and acid volume it was possible to identify the following optimum conditions: temperature, 160 degrees C; power, 750 W; digestion time, 25 min; and, an aqua regia volume of 13 mL. These microwave digestion conditions were then applied to 19 samples obtained from a former industrial site in Newcastle upon Tyne. Of the range of potentially toxic elements present at the site as a consequence of former industrial activity (As, Cd, Cr, Cu, Mo, Ni, Pb and Zn), the majority of topsoil samples indicated elevated concentrations of one or more of these elements. In particular, data obtained using either inductively coupled plasma mass spectrometry or flame atomic absorption spectroscopy indicates the high and wide concentration of Pb on the site (188-60300 mg/kg). Comparing the resulting potentially toxic elements data with UK soil guidelines values (SGVs) suggests at least parts of the site represent areas of potential human health risk. It was found that lead soil values exceeded the SGV on 17 out of the 19 sampling sites; similarly for As 6 out of 19 sampling sites exceeded the SGV. While for Cd, Cr and Ni the soil levels were below the stated SGVs.


The Effect of Dietary Antioxidant Supplementation in Patients with Glaucoma.
Oxidative stress may be a risk factor for glaucoma, and many previous reports have suggested that antioxidants could be a promising treatment. Here, we investigated the effects of a novel supplement containing three food-derived antioxidants (hesperidin, crocetin, and Tamarindus indica) on markers of oxidative stress in patients with glaucoma. This study had a prospective, single arm design. Thirty Japanese glaucoma patients were recruited and given 4 tablets with ample water twice a day for 8 weeks. The treatment was stopped, and the subjects were followed for an additional 8 weeks. We measured biological antioxidant potential (BAP) with a free radical analyzer. We also measured urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG; a marker of oxidative DNA damage). Clinical laboratory data were measured in venous blood samples. Clinical parameters were also recorded. Comparisons used a one-way analysis of variance (ANOVA) followed by Dunnett's test. The 8-OHdG level was not reduced. We also divided the patients into groups with high or low oxidative stress. In patients with relatively high oxidative stress, the 8-OHdG level was significantly reduced at weeks 4, 8, 12, and 16 (P < 0.001, P < 0.01, P < 0.01, P < 0.01), and BAP was significantly elevated at weeks 8 and 12 (P = 0.03, P = 0.04). In patients with relatively low oxidative stress, the 8-OHdG level was not significantly reduced during supplement intake but was significantly elevated at weeks 12 and 16 (P =0.03, P = 0.04), while BAP was not significantly elevated. An 8-week oral course of antioxidant supplementation was effective in patients with a high oxidative stress level. Dietary supplementation could hold promise in the treatment of systemic oxidative stress-related diseases.


Genetic predisposition influences plasma lipids of participants on habitual diet, but not the response to reductions in dietary intake of saturated fatty acids.
SNPs identified from genome-wide association studies associate with lipid risk markers of cardiovascular disease. This study investigated whether these SNPs altered the plasma lipid response to diet in the 'RISCK' study cohort. Participants (n=490) from a dietary intervention to lower saturated fat by replacement with carbohydrate or monounsaturated fat, were genotyped for 39 lipid-associated SNPs. The association of each individual SNP, and of the SNPs combined (using genetic predisposition scores), with plasma lipid concentrations was assessed at baseline, and on change in response to 24 weeks on diets. The associations between SNPs and lipid concentrations were directionally consistent with previous findings. The genetic predisposition scores were associated with higher baseline concentrations of plasma total (P=0.02) and LDL (P=0.002) cholesterol, triglycerides (P=0.001) and apolipoprotein B (P=0.004), and with lower baseline concentrations of HDL cholesterol (P<0.001) and apolipoprotein A-I (P<0.001). None of the SNPs showed significant association with the reduction of plasma lipids in response to the dietary interventions and there was no evidence of diet-gene interactions. Results from this exploratory study have shown that increased genetic predisposition was associated with an unfavourable plasma lipid profile at baseline, but did not influence the improvement in lipid profiles by the low-saturated-fat diets.


Major Motivators and Sociodemographic Features of Women Undergoing Labiaplasty.
Influencing factors involved in the decision to undergo labiaplasty are evolving and show diversity among different settings and countries. Updated underlying motivators may assist in clinical decision-making and assessing outcomes from the patients' perspective. Herein, the main motivators of women undergoing labiaplasty and sociodemographic features are discussed. Seventy-one patients who were scheduled for labiaplasty were assessed via an open-ended, well-detailed questionnaire to determine the main motivational factors from the patients' perspective. Validated questionnaires to measure genital self-image, self-esteem, body appreciation, attitude toward having cosmetic surgery, sexual dysfunction, and body-dysmorphic disorder were performed. Half of the patients reported that they had an idea about the appearance of other women's genitalia (50.7%) and were influenced through the media (47.9%). The majority of those (71.8%) stated that they did not have normal genitalia and considered labiaplasty more than 6 months ago (88.7%). The pornography consumption rate in the last month was 19.7% and was significantly related with lower genital self-image and self-esteem. The main motivation was improvement in appearance (43.7%) and a better sexual life (26.8%). Patients reported aesthetic (52.1%), sexual (46.5%), and psychological (39.4%) reasons leading to their decision. Patient-reported 8-items of 11-item motivators for having labiaplasty were statistically consistent with validated questionnaires. The self-esteem and body appreciation of the patients were comparable to the literature. Genital self-image and sexual function were found to be impaired. The women's main motivator for labiaplasty was improvement in genital appearance integrated with their aesthetic and sexual demands. Eleven-item motivators derived from the statements of women seeking labiaplasty were determined in this study. Sociodemographic features and main motivators can conveniently be used as normative data for this population.


Mindfulness-based stress reduction for people with chronic diseases.
Mindfulness-based stress reduction (MBSR) is a structured group program that uses mindfulness meditation to improve well-being and alleviate suffering. This article reviews the impact of MBSR for people with chronic diseases. The review includes original research that was published in English and peer-reviewed and reported outcomes for adults with chronic diseases who had participated in an MBSR program. Fifteen studies were identified. Outcomes related to mental and physical health, well-being, and quality of life. The studies included different research designs, and used self-report and physiological outcome measures. Participants' clinical diagnoses included fibromyalgia, chronic pain, rheumatoid arthritis, type 2 diabetes, chronic fatigue syndrome, multiple chemical sensitivity, and cardiovascular diagnoses. All 15 studies found that participation in an MBSR program resulted in improvements. No negative change was reported between baseline and follow up. Outcomes in regard to specific variables were difficult to compare and equivocal. Overall, positive change predominated. Chronic diseases are associated with a range of unwelcome psychological and physical consequences. Participation in an MBSR program is likely to result in coping better with symptoms, improved overall well-being and quality of life, and enhanced health outcomes. As an adjunct to standard care, MBSR has potential for much wider application in Australian primary care settings.


Acute inferior wall myocardial infarction and percutaneous coronary intervention of the right coronary during active labor: a clinical report and review of the literature.
Acute myocardial infarction (AMI) is a rare event in women of childbearing age and has been estimated to occur at a rate of 1 in 10,000 women during pregnancy. First reported on in 1922, subsequent reports appeared in the literature indicating the unique features of this condition which can significantly affect both maternal and fetal outcomes. With the current maternal trend of childbearing at an older age, in addition to the effects of cigarette smoking, stress and cocaine use, the occurrence of AMI during pregnancy, albeit uncommon, can be expected to increase. In this article we describe a unique case of a 42-year-old woman with an acute inferior wall MI who underwent a percutaneous angioplasty and placement of a bare-metal stent during active labor. The patient tolerated the procedure well and underwent a successful cesarean section with delivery of twins. The subsequent discussion examines the clinical aspects of gestational and early postpartum AMI and reviews current strategies for both diagnosis and treatment.


Comparative evaluation of modern dosimetry techniques near low- and high-density heterogeneities.
The purpose of this study is to compare performance of several dosimetric meth-ods in heterogeneous phantoms irradiated by 6 and 18 MV beams. Monte Carlo (MC) calculations were used, along with two versions of Acuros XB, anisotropic analytical algorithm (AAA), EBT2 film, and MOSkin dosimeters. Percent depth doses (PDD) were calculated and measured in three heterogeneous phantoms. The first two phantoms were a 30 × 30 × 30 cm3 solid-water slab that had an air-gap of 20× 2.5 × 2.35 cm3. The third phantom consisted of 30 × 30 × 5 cm3 solid water slabs, two 30 × 30 × 5 cm3 slabs of lung, and one 30 × 30 × 1 cm3 solid water slab. Acuros XB, AAA, and MC calculations were within 1% in the regions with particle equilibrium. At media interfaces and buildup regions, differences between Acuros XB and MC were in the range of +4.4% to -12.8%. MOSkin and EBT2 measurements agreed to MC calculations within ~ 2.5%, except for the first cen-timeter of buildup where differences of 4.5% were observed. AAA did not predict the backscatter dose from the high-density heterogeneity. For the third, multilayer lung phantom, 6 MV beam PDDs calculated by all TPS algorithms were within 2% of MC. 18 MV PDDs calculated by two versions of Acuros XB and AAA differed from MC by up to 2.8%, 3.2%, and 6.8%, respectively. MOSkin and EBT2 each differed from MC by up to 2.9% and 2.5% for the 6 MV, and by -3.1% and ~2% for the 18 MV beams. All dosimetric techniques, except AAA, agreed within 3% in the regions with particle equilibrium. Differences between the dosimetric techniques were larger for the 18 MV than the 6 MV beam. MOSkin and EBT2 measurements were in a better agreement with MC than Acuros XB calculations at the interfaces, and they were in a better agreement to each other than to MC. The latter is due to their thinner detection layers compared to MC voxel sizes.


Apigenin Mitigates Intervertebral Disc Degeneration through the Amelioration of Tumor Necrosis Factor α (TNF-α) Signaling Pathway.
BACKGROUND Intervertebral disc degeneration (IDD) is a common spinal disease affected by environmental and lifestyle factors that has a significant pathological cascade toward inflammation and partial disability. There is currently no therapy that can completely restore the cellular derangement in IDD. Hence, in this study, the therapeutic effects of apigenin on IDD were evaluated using a rat model. MATERIAL AND METHODS Animals were separated into 4 groups: Grp 1, sham-operated control; Grp 2, IDD-induced; Grp 3, IDD-induced+apigenin treatment; Grp 4, apigenin control. The animals were assessed for inflammatory cytokines, chemokines, and prostaglandin signaling. RESULTS There were significant increases in the inflammatory cytokines IL-1ß, IL-2, IL-6, IL-8 and IL-17 in the IDD-induced group compared to that of control. Moreover, with increased levels of MMP-3, MMP-9, ADAMTS-4, and syndecan-4, the levels of TNF-alpha, IFN-γ, prostaglandin E2, and cyclooxygenase 2 were directly increased in the IDD-induced group. In contrast, apigenin protectively restored levels of prostaglandin signaling and reduced cytokine levels. In addition, nucleus pulposus cells cultured separately with either TNF-alpha inhibitor or apigenin significantly attenuated the levels of extracellular matrix proteins. CONCLUSIONS The reduction of cytokine levels under apigenin treatment suggests it may be a promising target drug therapy for the treatment of deleterious IDD conditions.


Partition of some key regulating services in terrestrial ecosystems: Meta-analysis and review.
Our knowledge about the functional foundations of ecosystem service (ES) provision is still limited and more research is needed to elucidate key functional mechanisms. Using a simplified eco-hydrological scheme, in this work we analyzed how land-use decisions modify the partition of some essential regulatory ES by altering basic relationships between biomass stocks and water flows. A comprehensive meta-analysis and review was conducted based on global, regional and local data from peer-reviewed publications. We analyzed five datasets comprising 1348 studies and 3948 records on precipitation (PPT), aboveground biomass (AGB), AGB change, evapotranspiration (ET), water yield (WY), WY change, runoff (R) and infiltration (I). The conceptual framework was focused on ES that are associated with the ecological functions (e.g., intermediate ES) of ET, WY, R and I. ES included soil protection, carbon sequestration, local climate regulation, water-flow regulation and water recharge. To address the problem of data normality, the analysis included both parametric and non-parametric regression analysis. Results demonstrate that PPT is a first-order biophysical factor that controls ES release at the broader scales. At decreasing scales, ES are partitioned as result of PPT interactions with other biophysical and anthropogenic factors. At intermediate scales, land-use change interacts with PPT modifying ES partition as it the case of afforestation in dry regions, where ET and climate regulation may be enhanced at the expense of R and water-flow regulation. At smaller scales, site-specific conditions such as topography interact with PPT and AGB displaying different ES partition formats. The probable implications of future land-use and climate change on some key ES production and partition are discussed.


Hearing, Listening, Action: Enhancing nursing practice through aural awareness education.
Abstract Noise overload within the clinical environment has been found to interfere with the healing process for patients, as well as nurses ability to effectively assess patients. Awareness and responsibility for noise production begins during initial nursing training and consequently a program to enhance aural awareness skills was designed for graduate entry nursing students in an Australian university. The program utilised an innovative combination of music education activities to develop the students' ability to distinguishing individual sounds (hearing), appreciate patient's experience of sounds (listening) and improve their auscultation skills and reduce the negative effects of noise on patients (action). Using a mixed methods approach, students' reported heightened auscultation skills and greater recognition of both patients' and clinicians' aural overload. Results of this pilot suggest that music education activities can assist nursing students to develop their aural awareness and to action changes within the clinical environment to improve the patient's experience of noise.


Impact of loss of removable dentures on oral health after the great East Japan earthquake: a retrospective cohort study.
The Great East Japan Earthquake in March 2011 destroyed many communities, and as a result many older victims lost their removable dentures. No previous studies have documented the prevalence of denture loss after a natural disaster or examined its negative impact. Therefore, investigation of the consequences of such a disaster on oral health is of major importance from a public health viewpoint. Three to five months after the disaster, questionnaire surveys were conducted in two coastal towns, Ogatu and Oshika, located in the area of Ishinomaki city, Miyagi prefecture. Among the survey participants, 715 individuals had used one or more removable dentures before the disaster, and these comprised the population analyzed. The effect of denture loss on oral health-related quality life (OHRQoL) was examined by a modified Poisson regression approach with adjustment for sex, age, subjective household economic status, dental caries, tooth mobility, psychological distress (K6), access to a dental clinic, physical activity, and town of residence. There were 123 (17.2%) participants who had lost their dentures. In comparison with participants who had not lost their dentures, those lacking dentures showed a significantly higher relative risk for eating difficulties (RR = 2.65, 95%CI = 1.90-3.69), speech problems (RR = 4.37, 95%CI = 2.46-7.76), embarrassment upon smiling, laughing, or showing their teeth (RR = 5.32, 95%CI = 2.34-12.1), emotional distress (RR = 2.38, 95%CI = 1.41-4.03), and problems related to social interaction (RR = 6.97, 95%CI = 1.75-27.7). Denture loss appeared to impair eating and speaking ability, thus discouraging communication with others. Public health intervention after major natural disasters should include dental care.


Obstructive sleep apnoea in adults.
Obstructive sleep apnoea (OSA) is characterised by repetitive closure of the upper airway, repetitive oxygen desaturations and sleep fragmentation. The prevalence of adult OSA is increasing because of a worldwide increase in obesity and the ageing of populations. OSA presents with a variety of symptoms the most prominent of which are snoring and daytime tiredness. Interestingly though, a significant proportion of OSA sufferers report little or no daytime symptoms. OSA has been associated with an increased risk of cardiovascular disease, cognitive abnormalities and mental health problems. Randomised controlled trial evidence is awaited to confirm a causal relationship between OSA and these various disorders. The gold standard diagnostic investigation for OSA is overnight laboratory-based polysomnography (sleep study), however, ambulatory models of care incorporating screening questionnaires and home sleep studies have been recently evaluated and are now being incorporated into routine clinical practice. Patients with OSA are very often obese and exhibit a range of comorbidities, such as hypertension, depression and diabetes. Management, therefore, needs to be based on a multidisciplinary and holistic approach which includes lifestyle modifications. Continuous positive airway pressure (CPAP) is the first-line therapy for severe OSA. Oral appliances should be considered in patients with mild or moderate disease, or in those unable to tolerate CPAP. New, minimally invasive surgical techniques are currently being developed to achieve better patient outcomes and reduce surgical morbidity. Successful long-term management of OSA requires careful patient education, enlistment of the family's support and the adoption of self-management and patient goal-setting principles.


HOMO-LUMO coupling: the fourth rule for highly effective molecular rectifiers.
Three rules for creating highly effective unimolecular rectifiers that utilize asymmetric anchoring groups have been proposed by Van Dyck and Ratner [Ratner et al., Nano Lett., 2015, 15, 1577-1584]. This study investigates their proposed rectification mechanism in a functionalised azafullerene system (4TPA-C60) and identifies a fourth rule. NEGF-DFT shows that 4TPA-C60 fulfills the three design rules and finds that a saturated bridge is not required to fulfil the third rule, contrary to previous belief. Instead a twisted-π bridge decouples the donor and acceptor states whilst still providing a high conductance pathway. The molecular junction has a calculated rectification ratio of 145 at a bias of ±1 V and the U-type rectification mechanism is driven by the pinning of the HOMO to the LUMO when the device is forward biased, but not when reverse biased. The switching behaviour is a result of a charge dipole forming at different interfaces for different bias directions. An additional design rule is thus proposed: charge transport should allow bias dependent coupling of filled to unfilled states. The findings in this work not only help in understanding charge transport in molecular rectifiers, but also have wider implications for the design of molecular resonant tunneling devices.


A new approach for combining knowledge from multiple coexpression networks of microRNAs.
MicroRNAs (miRNAs) are a class of small noncoding RNAs that are known to have critical functions across various biological processes. Simultaneous activities of multiple miRNAs can be monitored from their expression profiles under various conditions. We often build up coexpression networks from such profiles. Unfortunately, due to the change of experimental setups (or conditions), the expression profiles do change, and consequently, the patterns of the coexpression networks vary. To obtain a robust functional relationship between miRNAs, by integrating different coexpression networks in a systems biology approach, we have to combine them properly. Here, we evaluate the state-of-the-art techniques and propose a novel integrative measure, and a corresponding methodology, that might be useful for identifying the dependence between coexpression and functional similarity. We establish the results by evaluating the expression profiles of miRNAs taken from bone marrow samples of patients with leukemia. The findings highlight the potential of the integrative algorithm in analyzing the expression profiles of miRNAs for further study.


Deletion of the basement membrane heparan sulfate proteoglycan type XVIII collagen causes hypertriglyceridemia in mice and humans.
Lipoprotein lipase (Lpl) acts on triglyceride-rich lipoproteins in the peripheral circulation, liberating free fatty acids for energy metabolism or storage. This essential enzyme is synthesized in parenchymal cells of adipose tissue, heart, and skeletal muscle and migrates to the luminal side of the vascular endothelium where it acts upon circulating lipoproteins. Prior studies suggested that Lpl is immobilized by way of heparan sulfate proteoglycans on the endothelium, but genetically altering endothelial cell heparan sulfate had no effect on Lpl localization or lipolysis. The objective of this study was to determine if extracellular matrix proteoglycans affect Lpl distribution and triglyceride metabolism. We examined mutant mice defective in collagen XVIII (Col18), a heparan sulfate proteoglycan present in vascular basement membranes. Loss of Col18 reduces plasma levels of Lpl enzyme and activity, which results in mild fasting hypertriglyceridemia and diet-induced hyperchylomicronemia. Humans with Knobloch Syndrome caused by a null mutation in the vascular form of Col18 also present lower than normal plasma Lpl mass and activity and exhibit fasting hypertriglyceridemia. This is the first report demonstrating that Lpl presentation on the lumenal side of the endothelium depends on a basement membrane proteoglycan and demonstrates a previously unrecognized phenotype in patients lacking Col18.


A tunable azine covalent organic framework platform for visible light-induced hydrogen generation.
Hydrogen evolution from photocatalytic reduction of water holds promise as a sustainable source of carbon-free energy. Covalent organic frameworks (COFs) present an interesting new class of photoactive materials, which combine three key features relevant to the photocatalytic process, namely crystallinity, porosity and tunability. Here we synthesize a series of water- and photostable 2D azine-linked COFs from hydrazine and triphenylarene aldehydes with varying number of nitrogen atoms. The electronic and steric variations in the precursors are transferred to the resulting frameworks, thus leading to a progressively enhanced light-induced hydrogen evolution with increasing nitrogen content in the frameworks. Our results demonstrate that by the rational design of COFs on a molecular level, it is possible to precisely adjust their structural and optoelectronic properties, thus resulting in enhanced photocatalytic activities. This is expected to spur further interest in these photofunctional frameworks where rational supramolecular engineering may lead to new material applications.


Depression Screening Rates and Symptom Severity by Alcohol Use Among Primary Care Adult Patients.
Hazardous alcohol use with depression may exacerbate health conditions and complicate medical care. We examined the rate of depression screening by alcohol use severity among primary care patients screened for hazardous alcohol use and, among those screened, examined patterns of significant depressive symptoms. Using cross-sectional data from primary care patients (n = 2,894,906), we examined past-90-day alcohol use (number of typical drinking days/week and typical number of drinks consumed daily); depression screening rates (using the Patient Health Questionnaire 9 [PHQ-9]); and symptom severity, demographics, and prevalence of selected psychiatric diagnoses. Within 30 days of routine, in-clinic alcohol use screening by medical assistants, 2.4% (n = 68,686) of patients also completed a PHQ-9; these patients were more likely to be female, younger, white, Medicaid insured, and to have a nondepressive psychiatric diagnosis and a lower Charlson comorbidity score. Abstainers and moderate drinkers (1 to 7 drinks/week or 1 to 4 drinks/week for women and individuals >65 years or for men ≤65 years, respectively) were less likely than hazardous drinkers (exceeding weekly limits) to complete the PHQ-9 or to have significant depressive symptoms (PHQ-9 score ≥10). Nonwhite patients with higher Charlson comorbidity scores were more likely to endorse significant depressive symptoms. Only a small fraction of patients in this cohort were screened for depression. Nonwhite patients and those with higher comorbidity burden were more likely to report depression but less likely to be screened. These discrepancies between depression-screening rates and significant depressive symptoms suggest that screening for depression should be enhanced in these at-risk groups.


Evaluation and a predictive model of airborne fungal concentrations in school classrooms.
Exposure to airborne fungal products may be associated with health effects ranging from non-specific irritation of the respiratory tract or mucus membranes to inflammation provoked by specific fungal antigens. While concentrations of airborne fungi are frequently measured in indoor air quality investigations, the significance of these measurements in the absence of visual mold colonization is unclear. This study was undertaken to evaluate concentrations of airborne fungal concentrations in school classrooms within a defined geographic location in British Columbia, Canada, and to build a model to clarify determinants of airborne fungal concentration. All elementary schools within one school district participated in the study. Classrooms examined varied by age, construction and presence or absence of mechanical ventilation. Airborne fungal propagules were collected inside classrooms and outdoors. Variables describing characteristics of the environment, buildings and occupants were measured and used to construct a predictive model of fungal concentration. The classrooms studied were not visibly contaminated by fungal growth. The data were evaluated using available guidelines. However, the published guidelines did not take into account significant aspects of the local environment. For example, there was a statistically significant effect of season on the fungal concentrations and on the proportional representation of fungal genera. Rooms ventilated by mechanical means had significantly lower geometric mean concentrations than naturally ventilated rooms. Environmental (temperature, outdoor fungal concentration), building (age) and ventilation variables accounted for 58% of the variation in the measured fungal concentrations. A methodology is proposed for the evaluation of airborne fungal concentration data which takes into account local environmental conditions as an aid in the evaluation of fungal bioaerosols in public buildings.


Modelling nitrogen transformations in waters receiving mine effluents.
This paper presents a biogeochemical model developed for a clarification pond receiving ammonium nitrogen rich discharge water from the Boliden concentration plant located in northern Sweden. Present knowledge about nitrogen (N) transformations in lakes is compiled in a dynamic model that calculates concentrations of the six N species (state variables) ammonium-N (N(am)), nitrate-N (N(ox)), dissolved organic N in water (N(org)), N in phytoplankton (N(pp)), in macrophytes (N(mp)) and in sediment (N(sed)). It also simulates the rate of 16 N transformation processes occurring in the water column and sediment as well as water-sediment and water-atmosphere interactions. The model was programmed in the software Powersim using 2008 data, whilst validation was performed using data from 2006 to 2007. The sensitivity analysis showed that the state variables are most sensitive to changes in the coefficients related to the temperature dependence of the transformation processes. A six-year simulation of N(am) showed stable behaviour over time. The calibrated model rendered coefficients of determination (R(2)) of 0.93, 0.79 and 0.86 for N(am), N(ox) and N(org), respectively. Performance measures quantitatively expressing the deviation between modelled and measured data resulted in values close to zero, indicating a stable model structure. The simulated denitrification rate was on average five times higher than the ammonia volatilisation rate and about three times higher than the permanent burial of N(sed) and, hence, the most important process for the permanent removal of N. The model can be used to simulate possible measures to reduce the nitrogen load and, after some modification and recalibration, it can be applied at other mine sites affected by N rich effluents.


Sublingual immunotherapy for peanut allergy: Long-term follow-up of a randomized multicenter trial.
We previously reported the initial results of the first multicenter, randomized, double-blind, placebo-controlled clinical trial of peanut sublingual immunotherapy (SLIT), observing a favorable safety profile associated with modest clinical and immunologic effects in the first year. We sought to provide long-term (3-year) clinical and immunologic outcomes for our peanut SLIT trial. Key end points were (1) percentage of responders at 2 years (ie, could consume 5 g of peanut powder or a 10-fold increase from baseline), (2) percentage reaching desensitization at 3 years, (3) percentage attaining sustained unresponsiveness after 3 years, (4) immunologic end points, and (5) assessment of safety parameters. Response to treatment was evaluated in 40 subjects aged 12 to 40 years by performing a 10-g peanut powder oral food challenge after 2 and 3 years of daily peanut SLIT therapy. At 3 years, SLIT was discontinued for 8 weeks, followed by another 10-g oral food challenge and an open feeding of peanut butter to assess sustained unresponsiveness. Approximately 98% of the 18,165 doses were tolerated without adverse reactions beyond the oropharynx, with no severe symptoms or uses of epinephrine. A high rate (>50%) discontinued therapy. By study's end, 4 (10.8%) of 37 SLIT-treated participants were fully desensitized to 10 g of peanut powder, and all 4 achieved sustained unresponsiveness. Responders at 2 years showed a significant decrease in peanut-specific basophil activation and skin prick test titration compared with nonresponders. Peanut SLIT induced a modest level of desensitization, decreased immunologic activity over 3 years in responders, and had an excellent long-term safety profile. However, most patients discontinued therapy by the end of year 3, and only 10.8% of subjects achieved sustained unresponsiveness.


Chronic Cough Related to Acute Viral Bronchiolitis in Children: CHEST Expert Panel Report.
Acute bronchiolitis is common in young children, and some children develop chronic cough after their bronchiolitis. We thus undertook systematic reviews based on key questions (KQs) using the PICO (Population, Intervention, Comparison, Outcome) format. The KQs were: Among children with chronic cough (> 4 weeks) after acute viral bronchiolitis, how effective are the following interventions in improving the resolution of cough?: (1) Antibiotics. If so what type and for how long? (2) Asthma medications (inhaled steroids, beta2 agonist, montelukast); and (3) Inhaled osmotic agents like hypertonic saline? We used the CHEST expert cough panel's protocol and the American College of Chest Physicians (CHEST) methodological guidelines and GRADE framework. Data from the systematic reviews in conjunction with patients' values and preferences and the clinical context were used to form these suggestions. Delphi methodology was used to obtain consensus. Several studies and systematic reviews on the efficacy of the three types of interventions listed in the introduction were found but no data were relevant to our KQs. Thus, no recommendations on using the interventions above could be formulated. The panel made several consensus-based suggestions and identified directions for future studies to advance the field of managing chronic cough post-acute bronchiolitis in children.


Isothiocyanate-rich Moringa oleifera extract reduces weight gain, insulin resistance, and hepatic gluconeogenesis in mice.
Moringa oleifera (moringa) is tropical plant traditionally used as an antidiabetic food. It produces structurally unique and chemically stable moringa isothiocyanates (MICs) that were evaluated for their therapeutic use in vivo. C57BL/6L mice fed very high fat diet (VHFD) supplemented with 5% moringa concentrate (MC, delivering 66 mg/kg/d of MICs) accumulated fat mass, had improved glucose tolerance and insulin signaling, and did not develop fatty liver disease compared to VHFD-fed mice. MC-fed group also had reduced plasma insulin, leptin, resistin, cholesterol, IL-1β, TNFα, and lower hepatic glucose-6-phosphatase (G6P) expression. In hepatoma cells, MC and MICs at low micromolar concentrations inhibited gluconeogenesis and G6P expression. MICs and MC effects on lipolysis in vitro and on thermogenic and lipolytic genes in adipose tissue in vivo argued these are not likely primary targets for the anti-obesity and anti-diabetic effects observed. Data suggest that MICs are the main anti-obesity and anti-diabetic bioactives of MC, and that they exert their effects by inhibiting rate-limiting steps in liver gluconeogenesis resulting in direct or indirect increase in insulin signaling and sensitivity. These conclusions suggest that MC may be an effective dietary food for the prevention and treatment of obesity and type 2 diabetes.


Fit body and soul: a church-based behavioral lifestyle program for diabetes prevention in African Americans.
Faith-based initiatives for lifestyle change show promise in helping to promote healthy behaviors in African American communities. It has been suggested that faith communities and programs within faith communities can influence health care practices and health care planning especially in high risk, minority populations. African American individuals are more likely to attend and participate in faith-based services than Whites from similar backgrounds. Our proposed intervention, Fit Body and Soul, has been adopted and modified from the proven diabetes prevention program (DPP) lifestyle intervention program, and uses the church-community experiences of the "Body and Soul" study as a faith-based effort. The intervention has been developed keeping in mind the church mission and goal of being spiritually healthy and has adopted bible scripture to develop a 12-session intervention. In this article, we present the development of the church-based Fit Body and Soul behavioral lifestyle intervention using community-based participatory research in partnership with African American churches.


Relative dependence of different outputs of the Saccharomyces cerevisiae pheromone response pathway on the MAP kinase Fus3p.
Fus3p and Kss1p act at the end of a conserved signaling cascade that mediates numerous cellular responses for mating. To determine the role of Fus3p in different outputs, we isolated and characterized a series of partial-function fus3 point mutants for their ability to phosphorylate a substrate (Ste7p), activate Ste12p, undergo G1 arrest, form shmoos, select partners, mate, and recover. All the mutations lie in residues that are conserved among MAP kinases and are predicted to affect either enzyme activity or binding to Ste7p or substrates. The data argue that Fus3p regulates the various outputs assayed through the phosphorylation of multiple substrates. Different levels of Fus3p function are required for individual outputs, with the most function required for shmoo formation, the terminal output. The ability of Fus3p to promote shmoo formation strongly correlates with its ability to promote G1 arrest, suggesting that the two events are coupled. Fus3p promotes recovery through a mechanism that is distinct from its ability to promote G1 arrest and may involve a mechanism that does not require kinase activity. Moreover, catalytically inactive Fus3p inhibits the ability of active Fus3p to activate Ste12p and hastens recovery without blocking G1 arrest or shmoo formation. These results raise the possibility that in the absence of sustained activation of Fus3p, catalytically inactive Fus3p blocks further differentiation by restoring mitotic growth. Finally, suppression analysis argues that Kss1p contributes to the overall pheromone response in a wild-type strain, but that Fus3p is the critical kinase for all of the outputs tested.


Does aspirin consumption affect the presentation or severity of acute myocardial infarction?
While consumption of aspirin has been shown to decrease the occurrence of nonfatal cardiac events, the majority of studies have not demonstrated any impact of aspirin intake on cardiovascular mortality. The present population-based study explores the possibility that aspirin consumption affects the presentation and severity of acute myocardial infarction (AMI), and hence the likelihood of clinical detection. We monitored the use of aspirin before admission for 2114 patients with a validated diagnosis of AMI in 16 hospitals in the Worcester, Mass, metropolitan area during 1986, 1988, and 1990. The AMIs were characterized as Q wave vs non-Q wave and large (peak creatine kinase levels more than five times normal) vs small (peak creatine kinase levels less than two times normal). A total of 332 patients (16%) with validated AMI took aspirin before hospital admission. Nearly 65% of aspirin users had non-Q wave AMIs, compared with 49% of nonaspirin users. Thirty percent of aspirin users sustained small AMIs, compared with 22% of nonaspirin users. These findings persisted after stratifying for previous AMI, history of coronary disease, receipt of thrombolytic therapy, and exclusion of early hospital deaths. Using multivariable regression models to control for age, gender, previous evidence of coronary disease, and use of other medications, prior aspirin consumption remained independently associated with AMI type (non-Q-wave AMI) and smaller infarct size. Aspirin consumption appears to modify the presentation of AMI, increasing the likelihood that the infarct will be of the small, non-Q-wave variety.


Sexual size dimorphism in anurans.
Several hypotheses have been proposed to explain the direction and extent of sexual size dimorphism in anurans (in which males are usually smaller than females) as a result of sexual selection. Here, we present an analysis to test the hypothesis that sexual dimorphism in anurans is largely a function of differences between the sexes in life-history strategies. Morphological and demographic data for anurans were collected from the literature, and the mean size and age in each sex were calculated for 51 populations, across 30 species and eight genera. Comparisons across 14 Rana species, eight Bufo species and across the genera showed a highly significant relationship between size dimorphism, measured using the female-male size ratio, and mean female-male age difference. A comparison of a subset of 17 of these species for which phylogenetic information was available, using the method of independent contrasts, yielded a similar result. These results indicate that most of the variation in size dimorphism in the anura can be explained in terms of differences in the age structure between the sexes in breeding populations. If sexual selection has an effect on size dimorphism in anurans, it is likely to be only a secondary one.


Activation of the lectin pathway of complement in experimental human keratitis with Pseudomonas aeruginosa.
Pseudomonas aeruginosa (P. aeruginosa) microbial keratitis (MK) is a sight-threatening disease. Previous animal studies have identified an important contribution of the complement system to the clearance of P. aeruginosa infection of the cornea. Mannose-binding lectin (MBL), a pattern recognition receptor of the lectin pathway of complement, has been implicated in the host defense against P. aeruginosa. However, studies addressing the role of the lectin pathway in P. aeruginosa MK are lacking. Hence, we sought to determine the activity of the lectin pathway in human MK caused by P. aeruginosa. Primary human corneal epithelial cells (HCECs) from cadaveric donors were exposed to two different P. aeruginosa strains. Gene expression of interleukin (IL)-6, IL-8, MBL, and other complement proteins was determined by reverse transcription-polymerase chain reaction (RT-PCR) and MBL synthesis by enzyme-linked immunosorbent assay and intracellular flow cytometry. MBL gene expression was not detected in unchallenged HCECs. Exposure of HCECs to P. aeruginosa resulted in rapid induction of the transcriptional expression of MBL, IL-6, and IL-8. In addition, expression of several complement proteins of the classical and lectin pathways, but not the alternative pathway, were upregulated after 5 h of challenge, including MBL-associated serine protease 1. However, MBL protein secretion was not detectable 18 h after challenge with P. aeruginosa. MK due to P. aeruginosa triggers activation of MBL and the lectin pathway of complement. However, the physiologic relevance of this finding is unclear, as corresponding MBL oligomer production was not observed.


Molecular identification of bacteria by total sequence screening: determining the cause of death in ancient human subjects.
Research of ancient pathogens in ancient human skeletons has been mainly carried out on the basis of one essential historical or archaeological observation, permitting specific pathogens to be targeted. Detection of ancient human pathogens without such evidence is more difficult, since the quantity and quality of ancient DNA, as well as the environmental bacteria potentially present in the sample, limit the analyses possible. Using human lung tissue and/or teeth samples from burials in eastern Siberia, dating from the end of 17(th) to the 19(th) century, we propose a methodology that includes the: 1) amplification of all 16S rDNA gene sequences present in each sample; 2) identification of all bacterial DNA sequences with a degree of identity ≥ 95%, according to quality criteria; 3) identification and confirmation of bacterial pathogens by the amplification of the rpoB gene; and 4) establishment of authenticity criteria for ancient DNA. This study demonstrates that from teeth samples originating from ancient human subjects, we can realise: 1) the correct identification of bacterial molecular sequence signatures by quality criteria; 2) the separation of environmental and pathogenic bacterial 16S rDNA sequences; 3) the distribution of bacterial species for each subject and for each burial; and 4) the characterisation of bacteria specific to the permafrost. Moreover, we identified three pathogens in different teeth samples by 16S rDNA sequence amplification: Bordetella sp., Streptococcus pneumoniae and Shigella dysenteriae. We tested for the presence of these pathogens by amplifying the rpoB gene. For the first time, we confirmed sequences from Bordetella pertussis in the lungs of an ancient male Siberian subject, whose grave dated from the end of the 17(th) century to the early 18(th) century.


Construction of relatedness matrices using genotyping-by-sequencing data.
Genotyping-by-sequencing (GBS) is becoming an attractive alternative to array-based methods for genotyping individuals for a large number of single nucleotide polymorphisms (SNPs). Costs can be lowered by reducing the mean sequencing depth, but this results in genotype calls of lower quality. A common analysis strategy is to filter SNPs to just those with sufficient depth, thereby greatly reducing the number of SNPs available. We investigate methods for estimating relatedness using GBS data, including results of low depth, using theoretical calculation, simulation and application to a real data set. We show that unbiased estimates of relatedness can be obtained by using only those SNPs with genotype calls in both individuals. The expected value of this estimator is independent of the SNP depth in each individual, under a model of genotype calling that includes the special case of the two alleles being read at random. In contrast, the estimator of self-relatedness does depend on the SNP depth, and we provide a modification to provide unbiased estimates of self-relatedness. We refer to these methods of estimation as kinship using GBS with depth adjustment (KGD). The estimators can be calculated using matrix methods, which allow efficient computation. Simulation results were consistent with the methods being unbiased, and suggest that the optimal sequencing depth is around 2-4 for relatedness between individuals and 5-10 for self-relatedness. Application to a real data set revealed that some SNP filtering may still be necessary, for the exclusion of SNPs which did not behave in a Mendelian fashion. A simple graphical method (a 'fin plot') is given to illustrate this issue and to guide filtering parameters. We provide a method which gives unbiased estimates of relatedness, based on SNPs assayed by GBS, which accounts for the depth (including zero depth) of the genotype calls. This allows GBS to be applied at read depths which can be chosen to optimise the information obtained. SNPs with excess heterozygosity, often due to (partial) polyploidy or other duplications can be filtered based on a simple graphical method.


Progressive multifocal leukoencephalopathy and black fungus in a patient with rheumatoid arthritis without severe lymphocytopenia.
Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating brain infection caused by JC polyomavirus (JCV), primarily seen in patients with severely compromised cellular immunity. Clinical presentation varies depending on the affected white matter. PML prognosis is variable and effective treatments are lacking. A 75-year-old Chinese woman with type 2 diabetes mellitus, chronic kidney disease and rheumatoid arthritis, treated with low-dose methotrexate and prednisolone for 2.5 years, developed a Pleurostomophora richardsiae infection of her left arm. After 6 months of treating this rare black fungus infection with voriconazole, surgery and immunosuppression discontinuation, she presented with progressive afebrile encephalopathy with right-sided hemiparesis. There were no signs of inflammation or metabolic abnormalities. Brain magnetic resonance imaging revealed diffuse frontal white matter lesions and a cerebrospinal fluid PCR confirmed PML due to JC virus. Severe lymphopenia was never present, and at PML diagnosis, CD4 and CD8 T-cell counts were 454 mm-3 and 277 mm-3. CD8 T-cells were able to respond to JCV VP1 peptide stimulation with TNFα secretion. Peripheral B-cell count was only 8 mm-3. Mirtazapine and Maraviroc were started, but unfortunately, she rapidly deteriorated and died 5 weeks after PML diagnosis. Although peripheral lymphocyte counts were never low and CD4 T-cell count was close to normal, the persistent black fungus infection was a hallmark of severely compromised cellular immunity. The unexpected extremely low absolute B-cell count might suggest a protective role for B-cells. The paradoxical, clinical PML onset months after immunosuppressive discontinuation suggests that it was only discovered in the context of an immune reconstitution inflammatory syndrome.


Clinical utility of pressure feedback to socket design and fabrication.
The clinical utility of measuring pressure at the prosthetic socket-residual limb interface is currently unknown. This study aimed to identify whether measuring interface pressure during prosthetic design and fabrication results in closer agreement in pressure measurements between sockets made by different clinicians, and a reduction in pressure over areas of concern. It also investigated whether clinicians value knowing the interface pressure during the fabrication process. Mixed methods. Three prosthetists designed a complete prosthetic system for a transtibial residual limb surrogate. Standardised mechanical testing was performed on each prosthetic system to gain pressure measurements at four key anatomical locations. These measurements were provided to the clinicians, who subsequently modified their sockets as each saw fit. The pressure at each location was re-measured. Each prosthetist completed a survey that evaluated the usefulness of knowing interface pressures during the fabrication process. Feedback and subsequent socket modifications saw a reduction in the pressure measurements at three of the four anatomical locations. Furthermore, the pressure measurements between prosthetists converged. All three prosthetists found value in the pressure measurement system and felt they would use it clinically. Results suggest that sensors measuring pressure at the socket-limb interface has clinical utility in the context of informing prosthetic socket design and fabrication. If the technology is used at the check socket stage, iterative designs with repeated measurements can result in increased consistency between clinicians for the same residual limb, and reductions in the magnitudes of pressures over specific anatomical landmarks. This study provides new information on the value of pressure feedback to the prosthetic socket design process. It shows that with feedback, socket modifications can result in reduced limb pressures, and more consistent pressure distributions between prosthetists. It also justifies the use of pressure feedback in informing clinical decisions.


A novel multi-antigen virally vectored vaccine against Mycobacterium avium subspecies paratuberculosis.
Mycobacterium avium subspecies paratuberculosis causes systemic infection and chronic intestinal inflammation in many species including primates. Humans are exposed through milk and from sources of environmental contamination. Hitherto, the only vaccines available against Mycobacterium avium subspecies paratuberculosis have been limited to veterinary use and comprised attenuated or killed organisms. We developed a vaccine comprising a fusion construct designated HAV, containing components of two secreted and two cell surface Mycobacterium avium subspecies paratuberculosis proteins. HAV was transformed into DNA, human Adenovirus 5 (Ad5) and Modified Vaccinia Ankara (MVA) delivery vectors. Full length expression of the predicted 95 kDa fusion protein was confirmed. Vaccination of naïve and Mycobacterium avium subspecies paratuberculosis infected C57BL/6 mice using DNA-prime/MVA-boost or Ad5-prime/MVA-boost protocols was highly immunogenic resulting in significant IFN-gamma ELISPOT responses by splenocytes against recombinant vaccine antigens and a range of HAV specific peptides. This included strong recognition of a T-cell epitope GFAEINPIA located near the C-terminus of the fusion protein. Antibody responses to recombinant vaccine antigens and HAV specific peptides but not GFAEINPIA, also occurred. No immune recognition of vaccine antigens occurred in any sham vaccinated Mycobacterium avium subspecies paratuberculosis infected mice. Vaccination using either protocol significantly attenuated pre-existing Mycobacterium avium subspecies paratuberculosis infection measured by qPCR in spleen and liver and the Ad5-prime/MVA-boost protocol also conferred some protection against subsequent challenge. No adverse effects of vaccination occurred in any of the mice. A range of modern veterinary and clinical vaccines for the treatment and prevention of disease caused by Mycobacterium avium subspecies paratuberculosis are needed. The present vaccine proved to be highly immunogenic without adverse effect in mice and both attenuated pre-existing Mycobacterium avium subspecies paratuberculosis infection and conferred protection against subsequent challenge. Further studies of the present vaccine in naturally infected animals and humans are indicated.


Transporter associated with antigen-processing-1 (TAP1) alleles in Gorilla gorilla: diversification of the locus postspeciation.
The transporter associated with antigen-processing (TAP) proteins are required for the transport of cytosolic peptides into the endoplasmic reticulum for assembly with class I major histocompatibility molecules. In the rat, allelic variants of the TAP genes impart specificity to the process of peptide transport. However, differential transport has yet to be demonstrated with the human molecules. TAP genes from humans and rodents have been studied thus far; analysis of another species more closely related to humans is necessary for a clearer understanding of the evolution of TAP genes. Three TAP1 alleles from four gorilla cell lines were characterized in this study. There is limited genetic distance at the locus, either within the gorilla (0.2%) or between the two hominoid species (0.8%). Nucleotide substitution analysis demonstrates that TAP1 and TAP2 are evolving at comparable rates under similar selection pressures. This pattern is in marked contrast to that observed for MHC class I genes of hominoids or rodents. Although there is limited evidence for trans-species evolution of the gorilla locus, the bulk of the diversification occurred after speciation as evidenced by a lack of shared amino acid polymorphism with human homologues. An evolutionary scheme predicts that the ancestral hominoid TAP1 molecule most closely resembled the human TAP1*02011.


Effects of an exclusive breastfeeding intervention for six months on growth patterns of 4-5 year old children in Uganda: the cluster-randomised PROMISE EBF trial.
Breastfeeding promotion is regarded as one of the most effective interventions to improve child health, and could reduce under-5-mortality by 8 % globally. Few studies have assessed the health outcomes beyond infancy of interventions promoting exclusive breastfeeding. This study assessed growth in under-five children who participated in a cluster-randomised trial in Eastern Uganda (ClinicalTrials.gov.no.NCT00397150). In the intervention arm, peer counsellors promoted exclusive breastfeeding during the first 6 months of infancy. There were no interventions after 6 months of age. Mother-infant pairs were interviewed at visits scheduled at 3, 6, 12 and 24 weeks after birth and follow-up visits at 2 and 5 years, with 765 included in the analyses. The mean length/height-for-age and weight-for-age-z-score (HAZ, WAZ) decreased with increasing age in both the intervention and control arms. At the three weeks visit, HAZ in the intervention was -0.45 (-0.68;-0.21) and -0.32 (-0.56;-0.07) in the control arm. At the 2 year follow-up, the mean HAZ in the intervention was -1.85 (95 % CI -1.97;-1.73) compared to -1.61 (-1.87;-1.34) in the control. Similarly, at the 5 year follow-up, the mean HAZ in the intervention was -1.78 (-2.08;-1.47) compared to -1.53 (-1.79;-1.28) in the control arm. At the 2 year follow-up visit, 139 (45 %) were stunted (HAZ<-2) in the intervention compared to 109 (37 %) in the control arm, odds ratio (OR) 1.7 (1.1;2.4). Underweight (WAZ<-2) was also more common in the intervention arm than in the control at the five years follow-up (OR 1.7 (1.0;2.8)), with a mean WAZ of -1.28 (-1.47;-1.08) and -1.06 (-1.19;-0.92) in the intervention and control arm, respectively. While stunting was widespread at 2 and 5 years of age in both arms, it was more common in the intervention arm. It is questionable whether community-based support from lay people with short training and focussing only on exclusive breastfeeding, is an appropriate strategy to improve child health and development. ClinicalTrials.gov.no. NCT00397150 . Registered 7th of November 2006.


Accumulating microparticles and direct-writing micropatterns using a continuous-wave laser-induced vapor bubble.
Through the enhanced photothermal effect, which was achieved using a silver film, a low power weakly focused continuous-wave laser (532 nm) was applied to create a vapor bubble. A convective flow was formed around the bubble. Microparticles dispersed in water were carried by the convective flow to the vapor bubble and accumulated on the silver film. By moving the laser spot, we easily manipulated the location of the bubble, allowing us to direct-write micropatterns on the silver film with accumulated particles. The reported simple controllable accumulation method can be applied to bimolecular detection, medical diagnosis, and other related biochip techniques.


Fundus reflectometry for photocoagulation dosimetry.
A dosimetry technique has been developed which utilizes three-wavelength fundus reflectometry, a quantitative model of fundus reflectance, and a model of thermal tissue damage to control photocoagulation lesion size. The fundus reflectance model uses Lambert-Beer's law exponential attenuators to describe the ocular media, retinal pigment epithelium (RPE), and choriocapillaris transmission characteristics while the choroid is described as a Kubelka-Munklike homogeneous scatterer/absorber. Three reflecting layers are included in the model at the retinal inner limiting membrane, Bruch's membrane, and the sclera. Measured lesion size variability contained components which resulted from variations in choroidal blood and melanin and RPE melanin concentration. Photocoagulation dosimetry was found to reduce the photocoagulation lesion size coefficient of variation for red light from 45% to 10% for the control and dosimetry cases, respectively. Similar improvement was noted for yellow photocoagulation light.


The Socio-Demographic Characteristics Associated with Non-Communicable Diseases among the Adult Population of Dubai: Results from Dubai Household Survey 2019.
Non-communicable diseases (NCDs) are the leading causes of death worldwide. In the UAE, NCDs account for nearly 77% of all deaths. There is limited empirical research on this topic in the UAE. We aimed to examine the association of non-communicable diseases and the sociodemographic characteristics among the adult population of Dubai. The study used secondary data from the Dubai Household Health Survey (DHHS), 2019. DHHS is a cross-sectional complex design, stratified by geographic area, and uses multistage probability sampling. In this survey, 2247 families were interviewed and only adults aged 18+ were included for the analysis. The quasi-binomial distribution was used to identify the socio-demographic characteristics association with NCDs. The prevalence of NCDs among the adult population of Dubai was 15.01%. Individuals aged 60+, local Arabs (Emirati), divorced and widowed individuals, and individuals who were not currently working reported NCDs more than the other groups. In the regression analysis, the association with NCDs were reported among elderly people, males, unmarried individuals, older individuals who are unmarried, and Emiratis. The study identified several socio-demographic characteristics associated with reporting NCDs. This is one of the few studies related to NCDs in Dubai. Allocating appropriate resources to the population groups identified is crucial to reduce the incidence of NCDs in the Emirate.


Effects of bradykinin and bradykinin analogs on the opossum lower esophageal sphincter: characterization of an inhibitory bradykinin receptor.
Bradykinin (BK) caused the circular muscle of opossum lower esophageal sphincter to relax and then contract in vitro. The effects of BK were not modified by indomethacin, tetrodotoxin, omega-conotoxin, atropine, propranolol, phentolamine, haloperidol, methysergide, pyrilamine or cimetidine. Apamin but not tetraethylammonium antagonized the inhibitory effect of BK and nifedipine antagonized its excitatory effect. Structure-activity relationships of 10 BK analogs known to be active on BK receptors were studied. Six analogs had distinct excitatory response profile and the rank order of potency of these agonists according to pD2 (shown in parentheses) was D-Arg-[Hyp3Thi5,8D-Phe7]-BK (6.49 +/- 0.19) greater than [Thi5,8D-Phe7]-BK (5.61 +/- 0.26) greater than Lys-Lys-[Hyp3-Thi5,8D-Phe7]-BK (5.45 +/- 0.14) greater than BK (5.16 +/- 0.20) greater than [des-Arg9]-BK (4.95 +/- 0.08) greater than [D-Phe7]-BK (4.73 +/- 0.10). However, only BK was fully efficacious (100%) and Emax values of all the analogs were less than that of BK. On the inhibitory response BK was the only agonist (pD2 = 5.48 +/- 0.08) and none of the BK analogs were agonist. All the BK analogs were also inactive as antagonists except Lys-Lys-[Hyp3-Thi5,8D-Phe7]-BK and Lys-Lys-[Hyp2,3-Thi5,8D-Phe7]-BK which competitively and selectively antagonized the BK inhibitory response. The pA2 value of Lys-Lys-[Hyp3-Thi5,8D-Phe7]-BK was 6.92 +/- 0.17.(ABSTRACT TRUNCATED AT 250 WORDS)


Dynamic changes in the response of cells to positive hedgehog signaling during mouse limb patterning.
In the vertebrate limb, the posteriorly located zone of polarizing activity (ZPA) regulates digit identity through the morphogen Sonic Hedgehog (Shh). By genetically marking Shh-responding cells in mice, we have addressed whether the cumulative influence of positive Shh signaling over time and space reflects a linear gradient of Shh responsiveness and whether Shh could play additional roles in limb patterning. Our results show that all posterior limb mesenchyme cells, as well as the ectoderm, respond to Shh from the ZPA and become the bone, muscle, and skin of the posterior limb. Further, the readout of Shh activator function integrated over time and space does not display a stable and linear gradient along the A-P axis, as in a classical morphogen view. Finally, by fate mapping Shh-responding cells in Gli2 and Gli3 mutant limbs, we demonstrate that a specific level of positive Hh signaling is not required to specify digit identities.


Direct and indirect effects of heatwaves on a coral reef fishery.
Marine heatwaves are increasing in frequency and intensity, and indirectly impacting coral reef fisheries through bleaching-induced degradation of live coral habitats. Marine heatwaves also affect fish metabolism and catchability, but such direct effects of elevated temperatures on reef fisheries are largely unknown. We investigated direct and indirect effects of the devastating 2016 marine heatwave on the largest reef fishery operating along the Great Barrier Reef (GBR). We used a combination of fishery-independent underwater census data on coral trout biomass (Plectropomus and Variola spp.) and catch-per-unit-effort (CPUE) data from the commercial fishery to evaluate changes in the fishery resulting from the 2016 heatwave. The heatwave caused widespread, yet locally patchy, declines in coral cover, but we observed little effect of local coral loss on coral trout biomass. Instead, a pattern of decreasing biomass at northern sites and stable or increasing biomass at southern sites suggested a direct response of populations to the heatwave. Analysis of the fishery-independent data and CPUE found that in-water coral trout biomass estimates were positively related to CPUE, and that coral trout catch rates increased with warmer temperatures. Temperature effects on catch rates were consistent with the thermal affinities of the multiple species contributing to this fishery. Scaling-up the effect of temperature on coral trout catch rates across the region suggests that GBR-wide catches were 18% higher for a given level of effort during the heatwave year relative to catch rates under the mean temperatures in the preceding 6 years. These results highlight a potentially large effect of heatwaves on catch rates of reef fishes, independent of changes in reef habitats, that can add substantial uncertainty to estimates of stock trends inferred from fishery-dependent (CPUE) data. Overestimation of CPUE could initiate declines in reef fisheries that are currently fully exploited, and threaten sustainable management of reef stocks.


New mutations in the RAB28 gene in 2 Spanish families with cone-rod dystrophy.
The families evaluated in this study represent the second report of cone-rod dystrophy (CRD) cases caused by mutations in RAB28, a recently discovered gene associated with CRD. To determine the disease-causing gene in 2 families of Spanish descent presenting with CRD who do not have ABCA4 mutations. Molecular genetics and observational case studies of 2 families, each with 1 affected proband with CRD and 3 or 5 unaffected family members. The affected individual from each family received a complete ophthalmic examination including assessment of refractive errors and best-corrected visual acuity, biomicroscopy, color fundus photography, electroretinography analysis, and visual-evoked potential analysis. After complete sequencing of the ABCA4 gene with negative results, the screening for disease-causing mutations was performed by whole-exome sequencing. Possible disease-associated variants were determined by filtering based on minor allele frequency, predicted pathogenicity, and segregation analysis in all family members. The appearance of the macula was evaluated by clinical examination, fundus photography, and fundus autofluorescence imaging, and visual function was assessed by electroretinography. Disease-causing mutations were assessed by sequence analyses. Ophthalmologic findings included markedly reduced visual acuity, bull's eye maculopathy, foveal hyperpigmentation, peripapillary atrophy, dyschromatopsia, extinguished photopic responses, and reduced scotopic responses observed on electroretinography consistent with the CRD phenotype often associated with ABCA4 mutations. Although no ABCA4 mutations were detected in either patient, whole-exome sequencing analysis identified 2 new homozygous mutations in the recently described RAB28 gene, the c.172 + 1G>C splice site variant in IVS2 and the missense c.T651G:p.C217W substitution. Both variants were determined as deleterious by predictive programs and were segregated with the disease in both families. Sequencing of 107 additional patients of Spanish descent with CRD did not reveal other cases with RAB28 mutations. Deleterious mutations in RAB28 result in a classic CRD phenotype and are an infrequent cause of CRD in the Spanish population.


Management of Parkinson's disease in Ayurveda: Medicinal plants and adjuvant measures.
Medicinal plants like Mucuna pruriens L.(DC) and Withania somnifera L.(Dunal) have been used in traditional Ayurvedic medicine to manage neurodegenerative diseases like Parkinson's disease. The aim of this review is to share the role of Ayurveda's insights, traditional usage and contemporary investigations for translational, integrative applications to manage Idiopathic Parkinson's Disease. High impact journals for Parkinson's diseases, traditional textbooks from Ayurveda as well as relevant clinical and para clinical studies with botanicals are selectively incorporated to evolve the aforesaid translational application. . A. Parkinson's disease (PD) is a complex multi-system, neurodegenerative disease. Though predominantly perceived as a motor disease, it also has debilitating non- motor features, which are frequently missed and not treated. Major treatment goals are to increase striatal dopamine levels with precursor-substitution and/or reduce its breakdown. As the disease progresses, a steady increase in the dose of levodopa is inevitable. However, higher doses cause motor complications of dyskinesia and dystonia and compromise medical treatment. B. ROLE OF MUCUNA PRURIENS L.DC), THE MOST PROMISING BOTANICAL FROM AYURVEDA: Ayurveda offers a natural source of levodopa - the seeds of Mucuna pruriens L.(DC)- which have a long standing safe use in the condition. Its clinical studies have shown pharmacokinetic profile distinct from synthetic levodopa, which is likely to reduce the untoward motor complications. Additionally, its seed extracts have shown neuroprotective benefits which are unrelated to levodopa. C. AYURVEDIC REGIMENS AND MEDICINAL PLANTS FOR NEUROPROTECTIVE AND SYMPTOMATIC BENEFITS: Other regimens (Panchakarma) and medicinal plants used in Ayurveda have been subjected to exploratory studies with promising early results in the condition. The debilitating non motor symptoms in patients have shown response with one of the regimens - medicated oil enema (basti). Effects of two medicinal plants Withania somnifera(L.)Dunal and Curcuma longa Linn in Parkinson's Disease related models have been discussed in detail. We have also shared a shortlist of medicinal plants most likely to be useful in management of specific features of the disease such as cognitive decline, mood disorders, risk of osteoporosis amongst others. Ayurveda with its medicinal plants and treatment approaches, can strengthen the therapeutic armamentarium of PD to improve clinical outcomes, if these leads are systematically further investigated by well-designed longer term studies.


Descriptive study of HTLV infection in a population of pregnant women from the state of Pará, Northern Brazil.
In Brazil, studies have shown that HTLV seroprevalence among pregnant women varies from 0 to 1.8%. However, this seroprevalence was unknown in the State of Pará, Brazil. The present study describes, for the first time, the HTLV seroprevalence among pregnant women from the State of Pará, Northern Brazil. 13,382 pregnant women were submitted to HTLV screening during prenatal care, and those with non-seronegative results to anti-HTLV were submitted to Western blot (WB) test to confirm and separate HTLV-1 and HTLV-2 carriers. HTLV seroprevalence in the population of pregnant women was 0.3%, and HTLV-1 was identified in 95.3% of patients. The demographic profile of HTLV carriers was as follows: women with age between 20 and 40 years old (78.4%); residing in the metropolitan region of Belém, Pará (67.6%); and with educational level of high school (56.8%). Other variables related to infection were as follows: beginning of sexual intercourse between the age of 12 and 18 years old (64.9%) and have being breastfed for more than 6 months (51.4%). Most of the women studied had at least two previous pregnancies (35.1%) and no abortion (70.3%). Coinfections (syphilis and HIV) were found in 10.8% (4/37) of these pregnant women. Seroprevalence of HTLV infection in pregnant women assisted in basic health units from the State of Pará, Northern Brazil, was 0.3% similar to those described in other Brazilian studies. The variables related to infection were important indicators in identifying pregnant women with a higher tendency to HTLV seropositivity, being a strategy for disease control and prevention, avoiding vertical transmission.


Poliomyelitis in Oman. II. Toward eradication.
In the past decade, the Sultanate of Oman has experienced three outbreaks of paralytic poliomyelitis--a widespread polio type 1 epidemic in 1988/1989, four cases of polio type 3 in three different regions in 1991, and a localized type 1 outbreak in 1993. The lessons learnt from each of these epidemics have guided us to modify and improve our polio eradication activities. Currently, these activities include administration of five primary and three booster doses of trivalent oral polio vaccine, yearly national immunization campaigns (NIDs) since 1995 with coverage of >90%, localized immunization campaigns, acute flaccid paralysis (AFP) surveillance which involves reporting of all cases by facsimile to the Department of Surveillance within 24 h of detecting a case and weekly zero reporting from 22 sentinel sites, and virological testing of stool specimens of all AFP cases and their close contacts at the national, World Health Organization accredited laboratory. The cumulative success of these activities has resulted in Oman being free from polio for the past 6 years. However, the possibility of importation of wild poliovirus, particularly from southern and western Asia still exists.


Differential regulation by retinoic acid and calcium of transglutaminases in cultured neoplastic and normal human keratinocytes.
In five lines of cultured human squamous carcinoma cells, transglutaminase activity and envelope competence were highly sensitive to retinoic acid and calcium levels in the growth medium. In cells grown in low calcium medium, these measures of keratinocyte differentiation were reduced. Retinoic acid suppressed envelope competence but total transglutaminase activity was markedly reduced, slightly affected, or greatly stimulated depending upon the cell line and whether the cells were grown in low calcium or 1.8 mM calcium-containing medium. Examination by anion exchange chromatography of the transglutaminase activity in SCC-12B2 cultures showed that expression of the particulate form (type I) of the enzyme was greatly stimulated by calcium. The increase in this activity to high levels that occurs at confluence could be almost completely suppressed by retinoic acid in the medium. The soluble form (type II) in the SCC-12B2 cells was induced in growing or confluent cultures by retinoic acid independent of the calcium concentration in the medium, but the 50% effective concentration (100 nM) for its stimulation was approximately 50-fold higher than the 50% effective concentration for suppression of the type I enzyme (2 nM). Thus, these enzymes appear to be distinct and independently regulated. This conclusion is supported by the finding that SCC-4 and SCC-9 almost exclusively expressed types II and I forms, respectively. In contrast to the results with neoplastic cells, in cultured normal epidermal cells type I enzyme comprised the overwhelming majority of activity and was only partially (75-90%) suppressible by retinoic acid, while type II enzyme seemed poorly if at all stimulable. Thus, the SCC lines appear appropriate for studying biochemical mechanisms of action of certain physiological agents, the molecular basis for altered regulation of differentiated function in neoplastic cells, and the origin of diversity within tumors.


Detection of Geminiviruses in Sweetpotato by Polymerase Chain Reaction.
Geminivirus infection of sweetpotato (Ipomoea spp.) germplasm acquired from foreign regions is common. Graft inoculation of the indicator host, Ipomoea setosa, is the accepted detection method for these viruses, but the assay is laborious and requires up to 8 weeks. When infected sweetpotato is subjected to meristem tip culture to eliminate these viruses, the eradication rate is low. In this study, a polymerase chain reaction (PCR) detection assay was developed for the detection of geminiviruses in a variety of sweetpotato cultivars. Different methods were evaluated to extract nucleic acids suitable for PCR from Ipomoea spp., and a reliable and simple extraction method was developed for large-scale sample preparation. PCR products of the expected sizes were amplified from infected plants using degenerate and virus-specific primers, but not from noninoculated indicator plants. PCR assays using three primer pairs detected nine uncharacterized isolates of the geminiviruses in sweetpotato from Asia and America. However, the best PCR result was obtained with degenerate primers SPG1/SPG2, which detected a Taiwan isolate of Sweet potato leaf curl virus (SPLCV-Taiwan) in a sample diluted to 10-9. Viral identities of three amplicons from SPLCV-Taiwan were confirmed by sequencing. The degenerate primers had a broader detection range than virus-specific primers; therefore, they were used to detect geminiviruses in in vitro plantlets and greenhouse-grown sweetpotato plants, and in several Ipomoea hosts. PCR was shown to be as reliable for virus detection as grafting.


Microarray analysis of gene expression in eastern oyster (Crassostrea virginica) reveals a novel combination of antimicrobial and oxidative stress host responses after dermo (Perkinsus marinus) challenge.
Dermo disease, caused by Perkinsus marinus, is one of the most severe diseases of eastern oysters, Crassostrea virginica. It causes serious mortalities in both wild and aquacultured oysters. Using existing expressed sequence tag (EST) resources, we developed a 12K in situ oligonucleotide microarray and used it for the analysis of gene expression profiles of oysters during the interactions between P. marinus and its oyster host. Significant gene expression regulation was found at day 30 post-challenge in the eastern oyster. Putative identities of the differentially expressed genes revealed a set of genes involved in several processes including putative antimicrobial defenses, pathogen recognition and uptake, anti-oxidation and apoptosis. Consistent with results obtained from previous, smaller-scale experiments, expression profiles revealed a large set of genes likely involved in an active mitigating response to oxidative stress and apoptosis induced by P. marinus. Additionally, a unique galectin from C. virginica, CvGal, which serves as a preferential receptor for P. marinus trophozoites, was found to be significantly down-regulated in gill tissue of oysters with both light and heavy infection, suggesting an attempt to control parasite uptake and proliferation in the later stages of infection. Potential histone-derived antimicrobial responses to P. marinus were also revealed in the gene expression profiles.


Exploring resilience: strengths of trafficking survivors in Cambodia.
Western literature provides an array of information regarding resilience within at-risk youth. Resilience research within non-Western contexts, and more specifically with exploited youth, is more limited. Despite exploitation, some youth develop a hardy ability to overcome adversity, allowing them more mastery over their environments and even increased psychological steadfastness. This project involved exploring the protective factors of resilience and psychological functioning in Cambodian youth, specifically a group of 24 survivors of sexual trafficking and another group of 24 rural youth without reported exploitation. The ages of participants ranged from 13 to 22 years, with the average age being 15.62 years [standard deviation (SD=2.68)]. Results indicated resilience constructs (mastery and relatedness) correlated with psychological functioning (anxiety and depression), as expected. The sense of relatedness was moderately associated with age. Also, as predicted, the trafficked young women demonstrated more resilience and less pathology. Consistent with previous research, earlier trauma is believed to inoculate survivors of trauma against further stress, mobilize them to better confront adversity and reduce psychological disruptions. Understanding these issues can help in understanding the relationship between resilience factors and psychological functioning as well as the strengths of many trauma survivors. Their strengths are particularly useful for developing effective treatment protocols for traumatized youth from non-Western backgrounds.


Usefulness of whole-blood interferon-gamma assay and interferon-gamma enzyme-linked immunospot assay in the diagnosis of active pulmonary tuberculosis.
The aim of this study was to evaluate the usefulness of the whole-blood interferon-gamma assay (enzyme-linked immunosorbent assay [ELISA]) and interferon-gamma enzyme-linked immunospot assay (ELISPOT) based on early secretory antigenic target 6 and culture filtrate protein 10 in the diagnosis of active pulmonary tuberculosis (TB) in routine clinical practice. We conducted a prospective study enrolling 144 participants with suspected pulmonary TB in a tertiary referral hospital in Seoul, South Korea, to investigate the diagnostic sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of these tests. Clinical assessment, tuberculin skin test (TST), whole-blood interferon-gamma ELISA (QuantiFERON-TB Gold [QFT-G]; Cellestis Ltd; Victoria, Australia), and an ELISPOT assay (T SPOT.TB; Oxford Immunotec; Oxford, UK) were performed. Test results were compared with the final confirmed diagnoses. Active pulmonary TB was diagnosed in 67 of 144 participants (47%). Sensitivities of QFT-G and T SPOT.TB for active pulmonary TB were 89% (95% confidence interval [CI], 79 to 96%) and 92% (95% CI, 83 to 97%), respectively; and specificities were 49% (95% CI, 37 to 61%) and 47% (95% CI, 36 to 59%). NPVs of QFT-G (84%; 95% CI, 69 to 93%) and T SPOT.TB (87%; 95% CI, 73 to 96%) were higher than that of TST (64%; 95% CI, 51 to 76%) [p = 0.001 and p < 0.001, respectively]. High NPVs of QFT-G and T SPOT.TB for the diagnosis of active TB suggest the supplementary role of these tests for the diagnostic exclusion of active TB, although the low PPV limits their usefulness in routine clinical practice in South Korea, where the prevalence of latent TB infection is considerable.


Functional stoichiometry of Shaker potassium channel inactivation.
Shaker potassium channels from Drosophila are composed of four identical subunits. The contribution of a single subunit to the inactivation gating transition was investigated. Channels carrying a specific mutation in a single subunit can be labeled in a heterogeneous population and studied quantitatively with scorpion toxin sensitivity as a selection tag. Linkage within a single subunit of a mutation that removes the inactivation gate to a second mutation that affects scorpion toxin sensitivity demonstrates that only a single gate is necessary to produce inactivation. The inactivation rate constant for channels with a single gate was one-fourth that of channels with four gates. In contrast, the rate of recovery from inactivation was independent of the number of gates. It appears that each of the four open inactivation gates in a Shaker potassium channel is independent, but only one of the four gates closes in a mutually exclusive manner.


"Ectrogella" Parasitoids of the Diatom Licmophora sp. are Polyphyletic.
The diatom genera Licmophora and Fragilaria are frequent epiphytes on marine macroalgae and can be infected by intracellular parasitoids traditionally assigned to the oomycete genus Ectrogella. Much debate and uncertainty remains about the taxonomy of these oomycetes, not least due to their morphological and developmental plasticity. Here, we used single-cell techniques to obtain partial sequences of the parasitoids 18S and cox2 genes. The former falls into two recently identified clades of Pseudo-nitzschia parasites temporarily named OOM_1_2 and OOM_2, closely related to the genera of brown and red algal pathogens Anisolpidium and Olpidiopsis. A third group of sequences falls at the base of the red algal parasites assigned to Olpidiopsis. In one instance, two oomycete parasitoids seemed to co-exist in a single diatom cell; this co-occurrence of distinct parasitoid taxa not only within a population of diatom epiphytes, but also within the same host cell, possibly explains the ongoing confusion in the taxonomy of these parasitoids. We demonstrate the polyphyly of Licmophora parasitoids previously assigned to Ectrogella (sensu Sparrow, 1960) and show that parasites of red algae assigned to the genus Olpidiopsis are most likely not monophyletic. We conclude that combining single-cell microscopy and molecular methods is necessary for their full characterisation.


Heparin Saline Versus Normal Saline for Flushing and Locking Peripheral Venous Catheters in Decompensated Liver Cirrhosis Patients: A Randomized Controlled Trial.
A prospective randomized, controlled, single-blinded trial to compare the effectiveness and safety of heparin saline (HS) to those of normal saline (NS) as flushing and locking solutions for peripheral venous catheter (PVC) in decompensated liver cirrhosis (DLC) patients.Patients with DLC at our institution between April 2012 and March 2013 were enrolled after obtaining informed consent. The patients were randomly allocated into 2 groups: the NS group received preservative-free 0.9% sodium chloride as the flushing and locking solution, while the HS group received HS (50 U/mL). PVC-related events and the duration of PVC maintenance were compared between the 2 groups. Moreover, the preinfusion and postinfusion levels of prothrombin time (PT), activated partial thromboplastin time (APTT), and platelet (PLT) were also compared.A total of 32 and 36 DLC patients in the NS (125 PVCs) and HS (65 PVCs) groups, respectively, were analyzed. Baseline characteristics, including gender, age, Child-Pugh grade, PVC type and administration of anticoagulant, and irritant agents, were comparable between the 2 groups (P > 0.05). The maintenance times of the HS and NS groups were 80.27 ± 26.47 and 84.19 ± 29.32 hours, respectively (P = 0.397). Removal of PVC for abnormal reasons occurred in 30.7% and 22.4% of patients in the HS and NS groups (P = 0.208). The PVC occlusion rates were 6.2% and 5.6% in the HS and NS groups, respectively (OR = 1.11, 95% CI 0.31-3.92). The PT, APTT, and PLT levels were comparable between the 2 groups both before and after infusion (P > 0.05). Incremental analyses showed that Child-Pugh grade C might be a risk factor for the suppression of PLT in the HS group.We consider NS to be as effective as and safer than conventional HS for flushing and locking PVC in decompensated liver cirrhosis patients.


Iron and aluminum in Alzheimer's disease.
In this case presentation, a woman with high serum levels of aluminum was treated with chelation therapy with deferoxamine and ascorbic acid. This patient was initially bedridden and the clinical situation was complicated by epileptic seizures. After the chelation therapy, the clinical condition was ameliorated and the therapy continued without the correlation to aluminum serum levels. The role of metals in neurodegenerative disorders and the correlation between iron metabolism and amyloid beta peptide are described. This case suggests chelation therapy could represent a promising therapeutic option for this dramatic disease.


Noise and its effects on photoreceptor temporal contrast sensitivity at low light levels.
We studied photoreceptors in the locust (Schistocerca americanus) visual system to determine the extent to which quantal noise and intrinsic neural noise limit temporal sensitivity. Typical computational models of the temporal contrast sensitivity function are deterministic, reflect only filter characteristics, and lack explicit noise sources [J. Opt. Soc. Am. 58, 1133 (1968); Vision Res. 32, 1373 (1992)]. We report here that the temporal contrast sensitivity function, at low light levels, is not simply the reflection of a filter function. Our evidence suggests that, at low backgrounds, noise, in conjunction with temporal filtering, plays a role in shaping the temporal contrast sensitivity function. At a given low adaptation level, quantal noise limits sensitivity at low temporal frequencies, while intrinsic noise limits sensitivity at relatively higher temporal frequencies.


Cognitive Processing Therapy for Posttraumatic Stress Disorder Is Associated with Negligible Change in Subjective and Objective Sleep.
Background: Patients receiving Cognitive Processing Therapy (CPT), an evidence based therapy for posttraumatic stress disorder (PTSD), report improved sleep quality. However, the majority of studies have examined residual sleep disturbance via self-report surveys or separate items on PTSD measures. This study examined whether CPT delivered to veterans in a VA setting improved sleep indices using state-of-the-art objective and subjective insomnia measures. Participants: Participants were war veterans with a current PTSD diagnosis scheduled to begin outpatient individual or group CPT at two Veteran's Affairs (VA) locations (n = 37). Methods: Sleep symptom severity was assessed using the recommended research consensus insomnia assessment, the consensus daily sleep diary and actigraphy. PTSD symptomatology pre- and post-treatment were assessed using the Clinician Administered PTSD Scale. Results: A small to moderate benefit was observed for the change in PTSD symptoms across treatment (ESRMC = .43). Effect sizes for changes on daily sleep diary and actigraphy variables after CPT were found to be negligible (Range ESRMC = - .16 to .17). Sleep indices remained at symptomatic clinical levels post-treatment. Discussion: These findings support previous research demonstrating a need for independent clinical attention to address insomnia either before, during, or after PTSD treatment.