A yoga-based therapy program designed to improve body image among an outpatient eating disordered population: program description and results from a mixed-methods pilot study.
Poor body image is a critical barrier to eating disorder recovery. This pilot project was designed as a feasibility study to examine a novel group-based, therapeutic yoga and body image program (YBI) for addressing negative body image in those clinically diagnosed with an eating disorder (anorexia, bulimia nervosa, and other specified feeding or eating disorder) receiving outpatient level treatment at an eating disorder treatment center located in Minneapolis-St. Paul, Minnesota. Self-administered questionnaires were completed by 67 participants at the beginning and end of the 8-week series, to better understand the acceptability of the YBI program and its potential effects on body image and self-worth during outpatient eating disorder treatment. Quantitative survey questions assessed participants' body image concerns, while open-ended questions probed participants' experiences and the perceived impact of the yoga program on their body image. After completion of the yoga program, mean item scores on the body image concern survey improved: increases ranged from 0.3 to 0.8 points on a 5-point scale. In open-ended questions, participants described many positive changes to their body image. Participants reported that the yoga program improved their self-acceptance, self-awareness, confidence, emotional and physical strength, and was a positive form of release. Participants also discussed physical and emotional challenges of the yoga program and how they contributed to self-judgment, vulnerability, and confrontation of uncomfortable feelings. The results of this pilot study are promising and warrant consideration of more rigorous study designs to explore the potential of a body image specific therapeutic yoga program to aid those in eating disorder treatment to improve body image disturbances.


iPBS-Retrotransposon Markers in the Analysis of Genetic Diversity among Common Bean (Phaseolus vulgaris L.) Germplasm from Türkiye.
Beans are legumes that play extremely important roles in human nutrition, serving as good sources of protein, vitamins, minerals, and antioxidants. In this study, we tried to elucidate the genetic diversity and population structure of 40 Turkish bean (Phaseolus vulgaris L.) local varieties and 5 commercial cultivars collected from 8 different locations in Erzurum-Ispir by using inter-primary binding site (iPBS) retrotransposon markers. For molecular characterization, the 26 most polymorphic iPBS primers were used; 52 bands per primer and 1350 bands in total were recorded. The mean polymorphism information content was 0.331. Various diversity indices, such as the mean effective allele number (0.706), mean Shannon's information index (0.546), and gene diversity (0.361) revealed the presence of sufficient genetic diversity in the germplasm examined. Molecular analysis of variance (AMOVA) revealed that 67% of variation in bean germplasm was due to differences within populations. In addition, population structure analysis exposed all local and commercial bean varieties from five sub-populations. Expected heterozygosity values ranged between 0.1567 (the fourth sub-population) and 0.3210 (first sub-population), with an average value of 0.2103. In contrary, population differentiation measurement (Fst) was identified as 0.0062 for the first sub-population, 0.6372 for the fourth subpopulations. This is the first study to investigate the genetic diversity and population structure of bean germplasm in Erzurum-Ispir region using the iPBS-retrotransposon marker system. Overall, the current results showed that iPBS markers could be used consistently to elucidate the genetic diversity of local and commercial bean varieties and potentially be included in future studies examining diversity in a larger collection of local and commercial bean varieties from different regions.


ATP Acyl Phosphate Reactivity Reveals Native Conformations of Hsp90 Paralogs and Inhibitor Target Engagement.
Hsp90 is an ATP-dependent chaperone of widespread interest as a drug target. Here, using an LC-MS/MS chemoproteomics platform based on a lysine-reactive ATP acyl phosphate probe, several Hsp90 inhibitors were profiled in native cell lysates. Inhibitor specificities for all four human paralogs of Hsp90 were simultaneously monitored at their endogenous relative abundances. Equipotent inhibition of probe labeling in each paralog occurred at sites both proximal to and distal from bound ATP observed in Hsp90 cocrystal structures, suggesting that the ATP probe is assaying a native conformation not predicted by available structures. Inhibitor profiling against a comprehensive panel of protein kinases and other ATP-binding proteins detected in native cell lysates identified PMS2, a member of the GHKL ATPase superfamily as an off-target of NVP-AUY922 and radicicol. Because of the endogenously high levels of Hsp90 paralogs in typical cell lysates, the measured potency of inhibitors was weaker than published IC₅₀ values. Significant inhibition of Hsp90 required inhibitor concentrations above a threshold where off-target activity was detectable. Direct on- and off-target engagement was measured by profiling lysates derived from cells treated with Hsp90 inhibitors. These studies also assessed the downstream cellular pathway effects of Hsp90 inhibition, including the down regulation of several known Hsp90 client proteins and some previously unknown client proteins. Overall, the ATP probe-based assay methodology enabled a broad characterization of Hsp90 inhibitor activity and specificity in native cell lysates.


Age of peak performance in 50-km ultramarathoners - is it older than in marathoners?
Despite the increasing popularity of 50-km ultramarathons during the last few years, only limited information is available regarding the trends in its performance and participation. The aim of the present study was to examine the age of peak running performance in female and male 50-km ultramarathoners using second-order nonlinear regression analyses. Data from 494,414 runners (124,045 women and 370,369 men) who finished a 50-km ultramarathon between 1975 to 2016 were analyzed. When the top ten finishers in 1-year age-groups were analyzed, the age of peak running speed was 41 years in both women and men. When the fastest finishers in 1-year age-group intervals were analyzed, the age of peak running speed was 40 years in women and 39 years in men. In summary, the age of peak running speed in 50-km ultramarathoners is older than what has been reported by previous studies for marathons. Women seem to achieve the best race time in a 50-km ultramarathon later in life compared with men. These findings are of great practical value for coaches and fitness trainers when setting performance goals for 50-km ultramarathon runners.


Upward spirals of positive emotions and religious behaviors.
Positive emotions feel good and build psychological, social, and biological resources (Broaden-and-Build Theory, Fredrickson, 1998, 2013). People who identify as religious or spiritual value them and report feeling them frequently. They are also prevalent in religious and spiritual practices, such as prayer, meditation, and collective worship. We review the literature on the reciprocal relationship between positive emotions and religion/spirituality and identify individual differences predicting greater positive emotions derived from engaging in religious practices. We suggest that beyond building religious/spiritual people's well-being, positive emotions play a role in sustaining otherwise costly religious behaviors. We integrate our review in the proposed Upward Spiral Theory of Sustained Religious Practice.


[An immunocytochemical analysis of the hormonal status of animals transgenic for growth hormone genes and for a mini-gene of human growth hormone-releasing factor].
An immunocytochemical analysis of hormonal status of transgenic rats containing human growth hormone gene has been done. The enhanced expression of the endogenous growth hormone gene was demonstrated with poly- and monoclonal antibodies inside somatatropes of pituitary. No activity of the heterologous growth hormone gene was revealed in kidney, pancreas or liver as it might be expected according to specificity of MT1 and TAT promotors. Transgenic animals of F0, F1 and F2 generation exhibited disturbance of functional morphology of glucagon and insulin producing cells. Lymphocyte infiltration was found in pancreatic islets. The transgenic rabbits and swine with the gene of releasing factor of human growth hormone did not reveal any severe disturbance. Although one swine demonstrated alterations in glucagon producing cells and one rabbit revealed a disturbed morphology of the stomach tissues. The data are discussed in relation to general problems of transgene activity and interaction with endogenous homolog.


A national Delphi study: experiences of general practitioner (GP) trainees in the Republic of Ireland undertaking online small group learning as part of the GP Training Programme during COVID-19.
During the COVID-19 pandemic, GP training day release was redirected from face-to-face to an online setting. With this study, our aim was to assess trainee experiences of online small group learning and to make recommendations with regards to future GP training. A qualitative study using the Delphi survey technique, approved by the Irish College of General Practitioners (ICGP) Ethics Committee. A series of three sequential online questionnaires were sent to our trainee cohort in all 14 training schemes in Ireland. The first questionnaire explored GP trainee experiences and key themes were generated. Subsequent questionnaires were developed using these themes, with second and third round questionnaires establishing consensus on these experiences. In total, 64 GP trainees responded. Each training scheme was represented. Response rates for round 1 and 2 were 76% and 56% respectively, with round 3 currently underway. Trainees felt that online teaching was convenient, reduced commuting costs, and provided peer support. They also reported loss in unstructured discussion, practical teaching sessions and relationship building. Seven key themes were generated: future format of GP training; accessibility and flexibility; teaching experience; provision of GP training; support and collegiality; educational experience; and technical problems. There is a consensus that some online teaching should be retained for the future. Online teaching provided a continuation in training that was more convenient and accessible but affected social interactions and relationship building amongst trainees. Future online sessions could be utilised in a hybrid model of teaching going forward.


Correlations suggest low magnesium may lead to higher rates of type 2 diabetes in Indigenous Australians.
Diabetes accounts for a significant part of the morbidity and mortality experienced by Australian Aboriginal and Torres Strait Islander populations. Research over the past two decades has provided evidence of a clinical correlation between diabetes and low magnesium intake. Hypomagnesaemia is the most common electrolyte abnormality in diabetic outpatients and may be linked to the development of both macrovascular and microvascular diabetic complications. A diabetes risk reduction of 33%-34% has been found among those with diets highest in magnesium. This study examines the case for magnesium as a potential contributor to diabetes in Australia, especially among Aboriginal and Torres Strait Islander peoples. Specifically explored are associations between diabetes and the magnesium content of drinking water and diet, as well as climatic and socioeconomic factors that may impact on magnesium status including temperature, rainfall, education, employment and income. Queensland age-standardized death rates due to diabetes were correlated with the magnesium content of drinking water, maximum average temperature, rainfall, unemployment rate, proportion of population with post-school qualification, weekly income, and the percentage population identified as Indigenous. Multiple-pass 24-hour recalls from a convenience sample of 100 Indigenous patients at a regional centre were also analyzed to estimate dietary magnesium intake. The Indigenous nutrient intake was then compared with the Australian National Nutrition Survey estimates. Diabetes related mortality was significantly correlated to the percentage of the population identified as Indigenous (r = 0.675), to water magnesium levels (r = -.414), and to average maximum daily temperature (r = 0.579). The average daily magnesium intake in an Indigenous cohort from a regional centre was 248 mg (men: 267 mg +/- 17; women: 245 mg +/- 6 mg), significantly less than intakes observed in the 1995 National Nutrition Survey (p<.001). Although not representative of all Indigenous people, this study identified low dietary magnesium intake among an Indigenous cohort from a regional centre. We also found a significant correlation between the magnesium content of municipal water supplies and age-standardized deaths due to diabetes. We hypothesise that low magnesium dietary intake, compounded by inadequate magnesium replenishment in drinking water, may increase the risk of hypomagnesaemia in the Indigenous population of Queensland. The associations identified in this study support the hypothesis that magnesium may be a potential contributor to diabetes in Australia, especially among Indigenous people, and confirm the need for further research.


The Impact of Challenge Information Security Stress on Information Security Policy Compliance: The Mediating Roles of Emotions.
Information security policy (ISP) compliance of employees has a profound impact on organization. In the context of information technology innovation and information systems upgrade, employees' information security behavior is one of the most crucial elements in the information security management of organizations. Based on the two-dimensional model of challenge-hindrance stressor theory and affective events theory, this study explores the mediating effects of emotions on the relationship between challenge information security stress and ISP compliance. A field quasi-experimental method was used in this study. Materials include the Challenge Information Security Stress Scale, Information System Security Policy Compliance Scale, and Emotions Scale, which were used to form the two-stage questionnaire surveys. Data of 217 employees from three Chinese companies in Shanghai and Beijing that had passed certifications for information security management system (GB/t22080-2008/ISO/IEC 27001:2005) were collected. Bootstrapping method for multiple mediation models and the Process 3.0 plug-in of SPSS 20.0 were used for data analysis. The findings indicate that challenge information security stress has a positive effect on ISP compliance. Challenge information security stress has a positive effect on positive emotions and a negative effect on negative emotions. Positive emotions have mediating effect between challenge information security stress and ISP compliance, but negative emotions have no mediating effect. The research results expand the research scope of challenging stress in the two-dimensional model of challenge-hindrance stressor theory in the context of organizational information security. The findings reveal the mediating effect of positive emotions in challenge information security stress and ISP compliance relationship, which provides empirical support for the application of positive psychology in the field of management.


Liver fatty-acid-binding protein (L-FABP) gene ablation alters liver bile acid metabolism in male mice.
Although the physiological roles of the individual bile acid synthetic enzymes have been extensively examined, relatively little is known regarding the function of intracellular bile acid-binding proteins. Male L-FABP (liver fatty-acid-binding protein) gene-ablated mice were used to determine a role for L-FABP, the major liver bile acid-binding protein, in bile acid and biliary cholesterol metabolism. First, in control-fed mice L-FABP gene ablation alone increased the total bile acid pool size by 1.5-fold, especially in gall-bladder and liver, but without altering the proportions of bile acid, cholesterol and phospholipid. Loss of liver L-FABP was more than compensated by up-regulation of: other liver cytosolic bile acid-binding proteins [GST (glutathione S-transferase), 3alpha-HSD (3alpha-hydroxysteroid dehydrogenase)], key hepatic bile acid synthetic enzymes [CYP7A1 (cholesterol 7alpha-hydroxylase) and CYP27A1 (sterol 27alpha-hydroxylase)], membrane bile acid translocases [canalicular BSEP (bile salt export pump), canalicular MRP2 (multidrug resistance associated protein 2), and basolateral/serosal OATP-1 (organic anion transporting polypeptide 1)], and positive alterations in nuclear receptors [more LXRalpha (liver X receptor alpha) and less SHP (short heterodimer partner)]. Secondly, L-FABP gene ablation reversed the cholesterol-responsiveness of bile acid metabolic parameters such that total bile acid pool size, especially in gall-bladder and liver, was reduced 4-fold, while the mass of biliary cholesterol increased 1.9-fold. The dramatically reduced bile acid levels in cholesterol-fed male L-FABP (-/-) mice were associated with reduced expression of: (i) liver cytosolic bile acid-binding proteins (L-FABP, GST and 3alpha-HSD), (ii) hepatic bile acid synthetic enzymes [CYP7A1, CYP27A1 and SCP-x (sterol carrier protein-x/3-ketoacyl-CoA thiolase)] concomitant with decreased positive nuclear receptor alterations (i.e. less LXRalpha and more SHP), and (iii) membrane bile acid transporters (BSEP, MRP2 and OATP-1). These are the first results suggesting a physiological role for the major cytosolic bile acid-binding protein (L-FABP) in influencing liver bile metabolic phenotype and gall-bladder bile lipids of male mice, especially in response to dietary cholesterol.


Clinical epidemiological analysis of cohort studies investigating the pathogenesis of kidney disease.
In recent years, large cohort studies of patients with chronic kidney disease (CKD) have been established all over the world. These studies have attempted to analyze the pathogenesis of CKD using a large body of published evidence. The design of cohort studies is characterized by the measurement of the exposure prior to the occurrence of the outcome, which has the advantage of clarifying the temporal relationship between predictors and outcomes and estimating the strength of the causal relationship between predictors and multiple outcomes. Recent advances in biostatistical analysis methods, such as propensity scores and risk prediction models, are facilitating causal inference using higher quality evidence with greater precision in observational studies. In this review, we will discuss clinical epidemiological research of kidney disease based on the analysis of observational cohort data sets, with a focus on our previous studies.


Factors affecting passive monoclonal antibody therapy of Moloney sarcoma in BALB/c mice.
We have developed a syngeneic monoclonal antibody (MoAb) (244-19A) which retards growth and contributes to cures of BALB/c mice bearing Moloney sarcoma cell (MSC) tumors (S.J. Kennel, T. Lankford, and K.M. Flynn, Cancer Res., 43: 2843-2847, 1983). The 244-19A epitope has not been detected in normal tissue or in any cultured cell (other than MSC) tested, including 15 different BALB/c sarcomas. MoAb 244-19A remains in circulation for a relatively long time in normal mice (t1/2 = 3.8 days), but it is cleared faster from tumor-bearing mice (t1/2 = 1.7 days), indicating a specific interaction of the antibody with the tumor. The 244-19A epitope is very labile. Osmotic lysis of cells or fixation with ethanol abolishes antibody binding. Trypsin treatment or fixation with gluteraldehyde reduces activity by 80 to 90%. Results from immunoprecipitation of radioiodinated MSC surface proteins indicate that the 244-19A epitope may reside on a Mr 65,000 protein, distinct from the major C-type virus glycoprotein 70 of these cells. Several factors affecting passive MoAb therapy have been evaluated. Doses as low as 24 micrograms/ mouse demonstrated a significant therapeutic effect; however, larger doses up to 1.5 mg/mouse produced progressively more cures. Since MoAb 244-19A is syngeneic in BALB/c mice, fractionated doses of antibody can be given over long periods of time without a host response to the MoAb. Fractionated doses showed a slight advantage over single dose therapy, but the difference was not statistically significant (P less than 0.2). Passive MoAb therapy has been effective in nu/nu mice, in BALB/c mice depleted of complement with cobra venum factor, and in BALB/c mice irradiated with 399 rads of X-rays; thus, therapy did not require complement, B-cells, or a cytotoxic T- cell response. Although tumor growth was retarded in nu/nu mice (T-cell-deficient), complete cures of tumored animals could not be accomplished even with large, multiple doses of antibody, indicating that cytotoxic T-cells eliminate residual tumor cells resulting in cures of BALB/c mice. Treatment of BALB/c mice with silica to deplete macrophage function did not affect therapy with MoAb 244-19A; however, treated animals still retained about 30% of their original phagocytic function, so macrophages cannot be eliminated as a possible host effector function.


Clinical experience with the laser indirect ophthalmoscope.
Laser delivery through a binocular indirect ophthalmoscope is a relatively recent addition to the armamentarium in vitreoretinal work. Hitherto to our experience, it had not been used in this region. This paper documents our initial experience with a laser indirect ophthalmoscope used successfully in the retinal photocoagulation of patients with diabetic retinopathy, venous occlusions, peripheral retinal holes and lattice degenerations and in post-vitrectomy cases. We found that this mode of laser delivery offered the advantages of an increased field of view of the retina, improved access to the retinal periphery and better patient comfort. It enabled laser treatment of patients with physical or mental handicaps who are unable to sit at the slit-lamp. It is the first system that can deliver laser treatment to patients in the pediatric age-group. It may also be valuable in Stage III retinopathy of prematurity, Coats disease, pneumatic retinopexy, and anterior hyaloidal neovascular proliferations. The chief drawback with this system are the lower magnification and sensitivity to inadvertent movement by the patient or surgeon. We concluded that this mode of laser delivery is a useful adjunct to the slit lamp system and can in some cases be the preferred mode of laser therapy.


Management and prognosis of borderline ovarian Brenner tumors.
The borderline ovarian Brenner tumor (BOBT) of the ovary is a rare tumor, and fewer than 25 cases have been reported in the literature. The aim of this study was to determine the prognosis of a series of BOBT collected in 2 reference centers. A retrospective review of patients with BOBT treated or referred to our institutions. A centralized histological review by a reference pathologist and data on the clinical characteristics, management, and outcomes of patients were required for inclusion. Ten patients were identified between 2000 and 2010. The median age of patients was 69 years (range, 52-84 years). Eight patients had pure BOBT and 2 had mixed histotype (mucinous and Brenner tumor). All patients had unilateral tumor and a stage I disease. No case of stromal microinvasion or intraepithelial carcinoma was observed. Among 5 patients with data on the follow-up, 1 lethal recurrence (50 months after initial surgery) was observed (the first reported in the literature). During the management of BOBT, peritoneal staging surgery is not required because all patients reported in the present series (and all but one in the literature) had stage I disease. One recurrence had occurred in this retrospective series. Nevertheless, among 35 cases (including those in the present study) reported in the literature with outcomes, this tumor carries a good prognosis. The power of this conclusion is, however, limited because of the relatively small number of patients studied (but this is a rare entity) and the short follow-up period.


DNA polymerase δ stalls on telomeric lagging strand templates independently from G-quadruplex formation.
Previous evidence indicates that telomeres resemble common fragile sites and present a challenge for DNA replication. The precise impediments to replication fork progression at telomeric TTAGGG repeats are unknown, but are proposed to include G-quadruplexes (G4) on the G-rich strand. Here we examined DNA synthesis and progression by the replicative DNA polymerase δ/proliferating cell nuclear antigen/replication factor C complex on telomeric templates that mimic the leading C-rich and lagging G-rich strands. Increased polymerase stalling occurred on the G-rich template, compared with the C-rich and nontelomeric templates. Suppression of G4 formation by substituting Li(+) for K(+) as the cation, or by using templates with 7-deaza-G residues, did not alleviate Pol δ pause sites within the G residues. Furthermore, we provide evidence that G4 folding is less stable on single-stranded circular TTAGGG templates where ends are constrained, compared with linear oligonucleotides. Artificially stabilizing G4 structures on the circular templates with the G4 ligand BRACO-19 inhibited Pol δ progression into the G-rich repeats. Similar results were obtained for yeast and human Pol δ complexes. Our data indicate that G4 formation is not required for polymerase stalling on telomeric lagging strands and suggest that an alternative mechanism, in addition to stable G4s, contributes to replication stalling at telomeres.


Metadta: a Stata command for meta-analysis and meta-regression of diagnostic test accuracy data - a tutorial.
Although statistical procedures for pooling of several epidemiological metrics are generally available in statistical packages, those for meta-analysis of diagnostic test accuracy studies including options for multivariate regression are lacking. Fitting regression models and the processing of the estimates often entails lengthy and tedious calculations. Therefore, packaging appropriate statistical procedures in a robust and user-friendly program is of great interest to the scientific community. metadta is a statistical program for pooling of diagnostic accuracy test data in Stata. It implements both the bivariate random-effects and the fixed-effects model, allows for meta-regression, and presents the results in tables, a forest plot and/or summary receiver operating characteristic (SROC) plot. For a model without covariates, it quantifies the unexplained heterogeneity due to between-study variation using an I2 statistic that accounts for the mean-variance relationship and the correlation between sensitivity and specificity. To demonstrate metadta, we applied the program on two published meta-analyses on: 1) the sensitivity and specificity of cytology and other markers including telomerase for primary diagnosis of bladder cancer, and 2) the accuracy of human papillomavirus (HPV) testing on self-collected versus clinician-collected samples to detect cervical precancer. Without requiring a continuity correction, the pooled sensitivity and specificity generated by metadta of telomerase for the diagnosis of primary bladder cancer was 0.77 [95% CI, 0.70, 0.82] and 0.91 [95% CI, 0.75, 0.97] respectively. Metadta also allowed to assess the relative accuracy of HPV testing on self- versus clinician-taken specimens using data from comparative studies conducted in different clinical settings. The analysis showed that HPV testing with target-amplification assays on self-samples was as sensitive as on clinician-samples in detecting cervical pre-cancer irrespective of the clinical setting. The metadta program implements state of art statistical procedures in an attempt to close the gap between methodological statisticians and systematic reviewers. We expect the program to popularize the use of appropriate statistical methods for diagnostic meta-analysis further.


Two years of bicalutamide monotherapy in patients with biochemical relapse after radical prostatectomy.
Salvage treatments for biochemical relapse (BCR) after radical prostatectomy (RP) have several problems in terms of indications or adverse events. We studied the possibility of 2 years of bicalutamide monotherapy for BCR after RP. Patients who showed BCR (prostate-specific antigen (PSA) ≥ 0.2 ng/ml) after RP were recruited. Protocol treatment was planned as 2 years of bicalutamide (80 mg/day) followed by observation. Protocol treatment failure was defined as PSA re-elevation of ≥0.2 ng/ml, clinical progression, any other treatments, or discontinuation or restart of bicalutamide. Primary endpoint of this study is time to protocol treatment failure from initiation of bicalutamide. A total of 91 patients were registered between 2003 and 2009. Median age and PSA at initiating bicalutamide were 68 (range, 55-78) years and 0.32 (range, 0.19-7.91) ng/ml. Twenty-four (26.4%) patients could not complete 2 years of bicalutamide mainly due to progression of disease. Of the 91 patients, 2- and 5-year protocol treatment failure-free survivals were 74.6% and 33.0%, with a median follow-up of 76 (range, 11-118) months. Median time from initiating bicalutamide to treatment failure was 43 (95% confidence interval, 33-47) months. High-risk status at RP and time to BCR after RP < 6 months were significant predictors of second BCR. Two years of bicalutamide monotherapy should not be recommended as standard management for BCR after RP, but might be feasible for selected patients who do not have high-risk status at RP and short time to BCR.


Feeding practices for toddlers with stunting in Jakarta: A case study.
Stunting represents a child's failure to thrive. On the basis of the World Health Organization child growth standards, stunting is a height of <-2 SD of the z-score for the child's age. There are several major causes of stunting. One is the inability to optimize child feeding practices. The aim of this study was to explore the feeding practices that lead to stunting in toddlers in Jakarta. The participants in this study were 15 mothers. Content analysis was the method that was chosen for this study. The data analysis revealed four themes that describe the feeding practices for toddlers with stunting in Jakarta: i) mothers providing instant porridge and ready-to-serve steamed chicken rice; ii) a feeding frequency of small portions only 2-3 times per day; iii) a lack of diet diversity; and iv) the suboptimal intake of iron-rich foods. The provision of effective education about appropriate feeding practices to pregnant women and mothers with toddlers is expected to reduce the incidence of stunting in Indonesia.


Frontal electroencephalogram alpha asymmetry during sleep: stability and its relation to affective style.
Electroencephalogram (EEG) alpha (8-12 Hz) asymmetries were collected from the mid-frontal and central regions during presleep wakefulness and Stage 1, Stage 2, and rapid eye movement (REM) sleep in 11 healthy right-handed participants who were free of psychiatric, neurological, and sleep problems. The authors found significant correlations between presleep wakefulness and different stages of sleep in the frontal, but not central, EEG alpha asymmetry measure. The strongest correlation was between presleep waking and REM sleep, replicating and extending relation earlier work to a normal population. The high degree of association between presleep waking and REM sleep may be a result of high cortical activation common to these states and may reflect a predisposition to different styles of emotional reactivity.


[Trends of tuberculosis morbidity and mortality in Russia in 2005].
The most informative indices; such as tuberculosis morbidity and mortality, were used to assess the tuberculosis epidemiological situation in Russia in 2005. Analysis of the rates of tuberculosis morbidity and mortality showed that the epidemic situation associated with tuberculosis remained to be of strain in Russia in 2005. This is evidenced by high tuberculosis morbidity and mortality rates and their increase. In 2005, there was a considerable rise in the frequency of recurrent tuberculosis and, as before, the high incidence of extrapulmonary tuberculosis, such as tuberculosis of the meninx, central nervous system, and bones and joints, in children aged 0-14 years. In 2005, as in previous years, the peak of tuberculosis morbidity was seen in young age groups (25-45 years) irrespective of gender. In 2005 versus 2004, a 3.8% increase in tuberculosis mortality was due to higher death rates among patients with chronic tuberculosis.


Trust and shared decision-making among individuals with multiple myeloma: A qualitative study.
Multiple myeloma (MM) is an incurable cancer with complex treatment options. Trusting patient-clinician relationships are essential to promote effective shared decision-making that aligns best clinical practices with patient values and preferences. This study sought to shed light on the development of trust between MM patients and clinicians. Nineteen individual semi-structured interviews were conducted with MM patients within 2 years of initial diagnosis or relapse for this qualitative study. Interviews were recorded and transcripts were coded thematically. We identified three main themes: (1) externally validated trust describes patients' predisposition to trust or distrust clinicians based on factors outside of patient-clinician interactions; (2) internally validated trust describes how patients develop trust based on interactions with specific clinicians. Internally validated trust is driven primarily by clinician communication practices that demonstrate competence, responsiveness, listening, honesty, and empathy; and (3) trust in relation to shared decision-making describes how patients relate the feeling of trust, or lack thereof, to the process of shared decision-making. Many factors contribute to the development of trust between MM patients and clinicians. While some are outside of clinicians' control, others derive from clinician behaviors and interpersonal communication skills. These findings suggest the possibility that trust can be enhanced through communication training or shared decision-making tools that emphasize relational communication. Given the important role trust plays in shared decision-making, clinicians working with MM patients should prioritize establishing positive, trusting relationships.


Global cropland and greenhouse gas impacts of UK food supply are increasingly located overseas.
Producing sufficient, healthy food for a growing world population amid a changing climate is a major challenge for the twenty-first century. Agricultural trade could help alleviate this challenge by using comparative productivity advantages between countries. However, agricultural trade has implications for national food security and could displace environmental impacts from developed to developing countries. This study illustrates the global effects resulting from the agricultural trade of a single country, by analysing the global cropland and greenhouse gas impacts of the UK's food and feed supply. The global cropland footprint associated with the UK food and feed supply increased by 2022 kha (+23%) from 1986 to 2009. Greenhouse gas emissions (GHGE) associated with fertilizer and manure application, and rice cultivation remained relatively constant at 7.9 Mt CO2e between 1987 and 2008. Including GHGE from land-use change, however, leads to an increase from 19.1 in 1987 to 21.9 Mt CO2e in 2008. The UK is currently importing over 50% of its food and feed, whereas 70% and 64% of the associated cropland and GHGE impacts, respectively, are located abroad. These results imply that the UK is increasingly reliant on external resources and that the environmental impact of its food supply is increasingly displaced overseas.


Implications of DNA replication for eukaryotic gene expression.
DNA replication has a key role in many developmental processes. Recent progress in understanding events at the replication fork suggests mechanisms for both establishing and maintaining programs of eukaryotic gene activity. In this review, I discuss the consequences of replication fork passage for preexisting chromatin structures and describe how the mechanism of nucleosome assembly at the replication fork may facilitate the formation of either transcriptionally active or repressed chromatin.


In vitro comparison of cell proliferation kinetics and uptake of tritiated fluorodeoxyglucose and L-methionine in squamous-cell carcinoma of the head and neck.
Estimation of tumor proliferative activity is important for the optimal management of head and neck cancer. Noninvasive metabolic imaging with PET may complement currently used cytopathologic methods to study tumor proliferation. Fluorodeoxyglucose (FDG) and L-methionine (MET) were studied for their potential to assess in vitro the growth characteristics of three squamous-cell carcinoma (SCC) cell lines established recently in patients with head and neck cancer. A time-course uptake of tritiated FDG and MET was measured over the complete growth cycle of one rapidly growing (UT-SCC-5) and two relatively slower growing (UT-SCC-1A and UT-SCC-9) cell lines. DNA flow cytometry was used for assessment of proliferative activity. There was a strong linear relationship for both FDG and MET uptake versus the viable cell number although absolute MET uptake was consistently lower than that of FDG in the exponential and plateau phases of growth (p < 0.01), leading MET to underestimate cell number. The pattern of MET uptake followed the flow cytometric changes in the proliferation index (% of S + G2/M cells) in two of three cases (UT-SCC-1A and UT-SCC-5) while a similar, although clearly weaker, relationship was seen with FDG and flow cytometry findings in only one case (UT-SCC-5). In these three human SCC cell lines assessed in vitro, FDG is a better marker of cell viability than MET, whereas MET is superior for estimating proliferative activity. Extrapolations of these in vitro data to the interpretation of PET images should be made with caution since tumors may have confounding factors that may affect in vivo tracer uptake.


An improved statistical model for taxonomic assignment of metagenomics.
With the advances in the next-generation sequencing technologies, researchers can now rapidly examine the composition of samples from humans and their surroundings. To enhance the accuracy of taxonomy assignments in metagenomic samples, we developed a method that allows multiple mismatch probabilities from different genomes. We extended the algorithm of taxonomic assignment of metagenomic sequence reads (TAMER) by developing an improved method that can set a different mismatch probability for each genome rather than imposing a single parameter for all genomes, thereby obtaining a greater degree of accuracy. This method, which we call TADIP (Taxonomic Assignment of metagenomics based on DIfferent Probabilities), was comprehensively tested in simulated and real datasets. The results support that TADIP improved the performance of TAMER especially in large sample size datasets with high complexity. TADIP was developed as a statistical model to improve the estimate accuracy of taxonomy assignments. Based on its varying mismatch probability setting and correlated variance matrix setting, its performance was enhanced for high complexity samples when compared with TAMER.


[Weight decrease in full-term newborns in the first 48 hours post natal].
It is known that the newborn (NB) presents weight loss immediately after birth. The magnitude of the weight loss is a controversial subject and there are no data in our sphere. Objecti ves: To determine the percentage of daily weight decrease in healthy full-term newborns in the first 48 hours of life. To specify whether factors such as gender, type of delivery, adequacy for gestational age, and use of milk formula influence weight loss. Prospective study in healthy full-term newborns with > 37 weeks of gestational age during their stay in the nursery (puerperium). Weight data were collected at birth, 24 and 48 hours after birth, and the percentages of weight loss were calculated from the daily nursing record. In addition, gender, type of delivery, adequacy to the birth and type of feeding of the NB, either exclusive breastfeeding, artificial formula or mixed (breast milk and formula) were recorded. To standardize the measurements, weights were expressed in grams and subsequently the percentage of weight loss was calculated in relation to the birth and the previous day. The maximum percentage of weight loss per day variable was analyzed. A multivariate regression model was performed for the weight loss percentages evolution. 2960 NB were analyzed. The average weight loss on the first day was 4.43% (SD: 1.96), the second day 2.51% (SD: 1.86) and the total loss at 48 hours was of 6.85% (DS: 1.92). The determining factor in weight loss was the type of delivery. The NBs by cesarean section showed a greater weight loss in the first 24 to 48 hours. The use of milk formula determines a smaller weight loss in the NB compared with those fed with breast milk (BM). The percentage of weight loss per day of the NB in our center is similar to that reported in the international literature. Cesarean delivery is the factor associated with greater weight loss. The use of milk formula results in less weight loss.


Differences between current clinical guidelines for screening, diagnosis and management of nonalcoholic fatty liver disease and real-world practice: a targeted literature review.
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease and is associated with obesity and metabolic comorbidities. Liver steatosis can progress to nonalcoholic steatohepatitis (NASH) exhibiting a relevant risk of fibrosis and ultimately liver failure. To date, no approved treatment for NASH to reduce its clinical and humanistic burden has been developed. We undertook a literature review to identify English language, national and international clinical guidelines for NAFLD regarding diagnosis, assessment and management, and determined their points of agreement and difference. Additionally, we investigated published literature relating to real-world management of NAFLD and NASH. National (China, England/Wales, Italy, the USA) and international society (Asia-Pacific, Europe, World Gastroenterology Organization) guidelines were identified and analyzed. All guidelines addressed identifying and diagnosing subjects with likely NAFLD, as well as assessment and management of individuals with risk factors for advanced disease, including fibrosis. Real-world practice reveals widespread suboptimal awareness and implementation of guidelines. In the absence of proven therapeutics, such gaps risk failure to recognize patients in need of specialist care and monitoring, highlighting the need for clear, easy-to-apply care pathways to aid in reducing the clinical and humanistic burden of NAFLD and NASH.


Renal complications in multiple myeloma and related disorders: survivorship care plan of the International Myeloma Foundation Nurse Leadership Board.
Kidney dysfunction is a common clinical feature of symptomatic multiple myeloma. Some degree of renal insufficiency or renal failure is present at diagnosis or will occur during the course of the disease and, if not reversed, will adversely affect overall survival and quality of life. Chronic insults to the kidneys from other illnesses, treatment, or multiple myeloma itself can further damage renal function and increase the risk for additional complications, such as anemia. Patients with multiple myeloma who have light chain (Bence Jones protein) proteinuria may experience renal failure or progress to end-stage renal disease (ESRD) and require dialysis because of light chain cast nephropathy. Kidney failure in patients with presumed multiple myeloma also may result from amyloidosis, light chain deposition disease, or acute tubular necrosis caused by nephrotoxic agents; therefore, identification of patients at risk for kidney damage is essential. The International Myeloma Foundation's Nurse Leadership Board has developed practice recommendations for screening renal function, identifying positive and negative contributing risk and environmental factors, selecting appropriate therapies and supportive care measures to decrease progression to ESRD, and enacting dialysis to reduce and manage renal complications in patients with multiple myeloma.


In vitro Digestion and Swelling Kinetics of Thymoquinone-Loaded Pickering Emulsions Incorporated in Alginate-Chitosan Hydrogel Beads.
The present work aimed to investigate the swelling behavior, in vitro digestion, and release of a hydrophobic bioactive compound, thymoquinone (TQ), loaded in Pickering emulsion incorporated in alginate-chitosan hydrogel beads using a simulated gastrointestinal model. In this study, oil-in-water Pickering emulsions of uniform micron droplet sizes were formulated using 20% red palm olein and 0.5% (w/v) cellulose nanocrystals-soy protein isolate (CNC/SPI) complex followed by encapsulation within beads. FT-IR was used to characterize the bonding between the alginate, chitosan, and Pickering emulsion. 2% (w/v) alginate-1% (w/v) chitosan hydrogel beads were found to be spherical with higher stability against structural deformation. The alginate-chitosan beads displayed excellent stability in simulated gastric fluid (SGF) with a low water uptake of ~19%. The hydrogel beads demonstrated a high swelling degree (85%) with a superior water uptake capacity of ~593% during intestinal digestion in simulated intestinal fluid (SIF). After exposure to SIF, the microstructure transformation was observed, causing erosion and degradation of alginate/chitosan wall materials. The release profile of TQ up to 83% was achieved in intestinal digestion, and the release behavior was dominated by diffusion via the bead swelling process. These results provided useful insight into the design of food-grade colloidal delivery systems using protein-polysaccharide complex-stabilized Pickering emulsions incorporated in alginate-chitosan hydrogel beads.


Interventions for the prevention of postoperative ear discharge after insertion of ventilation tubes (grommets) in children.
Grommets are frequently inserted in children's ears for acute otitis media and otitis media with effusion. A common complication is postoperative ear discharge (otorrhoea). A wide range of treatments are used to prevent the discharge, but there is no consensus on whether or not intervention is necessary nor which is the most effective intervention. To assess the effectiveness of prophylactic interventions, both topical and systemic, in reducing the incidence of otorrhoea following the surgical insertion of grommets in children. We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the search was 3 July 2012. We included randomised controlled trials (RCTs) that compared the efficacy of prophylactic interventions against placebo/control and/or with other prophylactic interventions for postoperative otorrhoea in children. Two review authors independently assessed study eligibility and risk of bias, and extracted data. The outcome data were dichotomous for all the included trials. We calculated individual and pooled risk ratios (RR) using the Mantel-Haenszel fixed-effect method. We also calculated the numbers needed to treat to benefit (NNTB). We found 15 eligible RCTs (2476 children, aged from four months to 17 years). We graded seven RCTs as being at a low risk of bias (n = 926 children) and for an eighth RCT we also graded two of the arms as being at a low risk of bias. We graded the other seven trials as being at a high risk of bias.For a single application at surgery, there was evidence from two low risk of bias trials that at two weeks postoperatively the risk of otorrhoea was reduced by multiple saline washouts (from 30% to 16%; RR 0.52, 95% confidence interval (CI) 0.27 to 1.00; NNTB 7; one RCT; 140 children) and antibiotic/steroid ear drops (from 9% to 1%; RR 0.13, 95% CI 0.03 to 0.57; NNTB 13; one RCT; 322 ears). A meta-analysis of two low risk of bias trials (222 ears) failed to find an effect of a single application of antibiotic/steroid ear drops at four to six weeks postoperatively.For a prolonged application of an intervention, there was evidence from four low risk of bias trials that the risk of otorrhoea was reduced two weeks postoperatively by antibiotic ear drops (from 15% to 8%; RR 0.54, 95% CI 0.30 to 0.97; NNTB 15; one RCT; 372 children), antibiotic/steroid ear drops (from 39% to 5%; RR 0.13, 95% CI 0.05 to 0.31; NNTB 3; one RCT; 200 children), aminoglycoside/steroid ear drops (from 15% to 5%; RR 0.37, 95% CI 0.18 to 0.74; NNTB 11; one RCT; 356 children) or oral antibacterial agents/steroids (from 39% to 5%; RR 0.13, 95% CI 0.03 to 0.51; NNTB 3; one RCT; 77 children).Only one trial assessed the secondary outcome of ototoxicity, but no effect was found. There were no trials that assessed quality of life. Our review found that each of the following were effective at reducing the rate of otorrhoea up to two weeks following surgery: (1) multiple saline washouts at surgery, (2) a single application of topical antibiotic/steroid drops at surgery, (3) a prolonged application of topical drops (namely antibiotic ear drops, antibiotic/steroid eardrops or aminoglycoside/steroid ear drops) and (4) a prolonged application of oral antibacterial agents/steroids. However, the rate of otorrhoea between RCTs varied greatly and the higher the rates of otorrhoea within a RCT, the smaller the NNTB for therapy.We conclude that if a surgeon has a high rate of postoperative otorrhoea in children then either saline irrigation or antibiotic ear drops at the time of surgery would significantly reduce that rate. If topical drops are chosen, it is suggested that to reduce the cost and potential for ototoxic damage this be a single application at the time of surgery and not prolonged thereafter.


COVID-19 and hereditary angioedema: Incidence, outcomes, and mechanistic implications.
Background: Patients with hereditary angioedema (HAE) have been postulated to be at increased risk for coronavirus disease 2019 (COVID-19) infection due to inherent dysregulation of the plasma kallikrein-kinin system. Only limited data have been available to explore this hypothesis. Objective: To assess the interrelationship(s) between COVID-19 and HAE. Methods: Self-reported COVID-19 infection, complications, morbidity, and mortality were surveyed by using an online questionnaire. The participants included subjects with HAE with C1 inhibitor (C1INH) deficiency (HAE-C1INH) and subjects with HAE with normal C1-inhibitor (HAE-nl-C1INH), and household controls (normal controls). The impact of HAE medications was examined. Results: A total of 1162 participants who completed the survey were analyzed, including: 695 subjects with HAE-C1INH, 175 subjects with HAE-nl-C1INH, and 292 normal controls. The incidence of reported COVID-19 was not significantly different between the normal controls (9%) and the subjects with HAE-C1INH (11%) but was greater in the subjects with HAE-nl-C1INH (19%; p = 0.006). Obesity was positively correlated with COVID-19 across the overall population (p = 0.012), with a similar but nonsignificant trend in the subjects with HAE-C1INH. Comorbid autoimmune disease was a risk factor for COVID-19 in the subjects with HAE-C1INH (p = 0.047). COVID-19 severity and complications were similar in all the groups. Reported COVID-19 was reduced in the subjects with HAE-C1INH who received prophylactic subcutaneous C1INH (5.6%; p = 0.0371) or on-demand icatibant (7.8%; p = 0.0016). The subjects with HAE-C1INH and not on any HAE medications had an increased risk of COVID-19 compared with the normal controls (24.5%; p = 0.006). Conclusion: The subjects with HAE-C1INH who were not taking HAE medications had a significantly higher rate of reported COVID-19 infection. Subcutaneous C1INH and icatibant use were associated with a significantly reduced rate of reported COVID-19. The results implicated potential roles for the complement cascade and tissue kallikrein-kinin pathways in the pathogenesis of COVID-19 in patients with HAE-C1INH.


The role of forensic anthropology in mass disaster resolution.
On Dec.12, 1985, a military charter DC-8 crashed shortly after takeoff at Gander, Nfld., Canada. All 256 aboard were killed, making this the deadliest U.S. military aircraft accident in history. The investigation team (consisting of forensic pathologists, odontologists, radiologists, anthropologists, graves registration personnel, and systems engineers) succeeded in identifying the remains of all 248 manifested passengers and 8 crewmembers. The unique contribution of anthropology necessitates that a forensic anthropologist be included in all phases of casualty resolution from recovery and initial processing to final evaluation, rather than being summoned as a last resort. This approach would yield immediate information on "unknowns" and would eliminate subsequent duplication of effort.


Modality-specific hyper-responsivity of regenerated cat cutaneous nociceptors.
1. Experiments were performed on anaesthetized cats to investigate the receptive properties of regenerated cutaneous tibial nerve nociceptors, and to obtain evidence for coupling between them and other afferent fibres as being possible peripheral mechanisms involved in neuropathic pain. These properties were studied 6-7 months after nerve section and repair. 2. Recordings were made from 25 regenerated nociceptors; 14 were A fibres and the remainder were C fibres. Their receptive field sizes and conduction velocities were similar to controls. There was no significant difference between their mechanical thresholds and those of a control population of nociceptors. 3. Regenerated nociceptors were significantly more responsive to suprathreshold mechanical stimuli than were uninjured control fibres. This increase in mechanical sensitivity occurred in both A and C fibres, although A fibres showed a greater increase in mechano-sensitivity than C fibres. Over half of the regenerated nociceptors (13/25) showed after-discharge to mechanical stimuli which was never seen in controls; the mean firing rate during this period of after-discharge was significantly related to both stimulus intensity and stimulus area. 4. There was no significant difference between the heat encoding properties of regenerated nociceptors and control nociceptors. Cold sensitivity was similarly unchanged. Thus, abnormal peripheral sprouting was unlikely to account for the increased mechanical sensitivity of the regenerated fibres. None of the regenerated nociceptors were found to be coupled to other fibres. 5. These results suggest that the clinical observation of mechanical hyperalgesia in patients after nerve injury may have a peripheral basis. Based on this model, other signs of neuropathic pain (i.e. tactile or thermal allodynia) are more likely to be due to altered central processing.


p53 abnormalities in adenocarcinoma of the gastric cardia and antrum.
To compare the frequency and type of p53 alterations (gene mutation and/or protein overexpression) in a consecutive series of surgically resected adenocarcinomas arising in the gastric cardia and gastric antrum, and to evaluate associations with clinicopathological findings (age, sex, and tumour histology, grade, and stage). The series comprised 50 patients with adenocarcinoma of the cardia and 20 patients with adenocarcinoma of the antrum. p53 gene mutations (exons 5-8) were detected by denaturing gradient gel analysis and DNA sequencing. Nuclear p53 overexpression was detected by immunohistochemistry with the DO7 antibody. p53 gene mutations were found in 21 of 50 and five of 20 adenocarcinomas of the cardia and the antrum, respectively. Base transitions occurring at CpG dinucleotides were frequent in both types of tumour. p53 protein overexpression was seen in 32 of 50 and seven of 20 adenocarcinomas of the cardia and of the antrum, respectively. p53 gene mutation and/or protein overexpression were significantly more frequent in adenocarcinomas of the cardia (37 of 50) than in adenocarcinomas of the antrum (seven of 20). There were no differences in the clinicopathological characteristics of the tumours between p53 positive and p53 negative cases in both types of cancer. This study shows that p53 alterations are more frequent in adenocarcinoma of the cardia than in adenocarcinoma of the antrum. This feature is consistent with the clinical and epidemiological characteristics of these cancers, which suggest that adenocarcinoma arising in the gastric cardia might be related to oesophageal adenocarcinoma, and unrelated to adenocarcinomas of the gastric body and antrum.


High-sensitivity flow cytometry provides access to standardized measurement of small-size microparticles--brief report.
Cellular microparticles (MP) are promising biomarkers in many pathological situations. Although flow cytometry (FCM) is widely used for their measurement, it has raised controversies because the smallest MP size falls below the detection limit of standard FCM (sd-FCM). Following recent technological improvements leading to high sensitivity FCM (hs-FCM), our objectives were (1) to evaluate the potential of hs-FCM for extended MP detection, (2) to set up a standardized protocol for MP enumeration, and (3) to compare MP counts obtained with both sensitivity levels. Compared with sd-FCM, hs-FCM displayed improved forward scatter resolution and lower background noise, allowing us to discriminate previously undetectable small MP in plasma samples. Using fluorescent beads with appropriate sizes (0.1/0.3/0.5/0.9 μm) and relative amounts, a new standardized hs-FCM MP protocol was set up and provided reproducible MP counts. Applied to coronary patient samples, it resulted into 8- to 20-fold increases in MP counts as compared with sd-FCM. Interestingly, the ratio between small and large MP varied according to clinical status but also depending on MP subset, suggesting access to new biological information. Recent improvements in FCM provide access to previously undetectable MP and represent a new opportunity to enhance their impact as biomarkers in clinical practice.


Individual Differences in Anticipatory Somatosensory Cortex Activity for Shock is Positively Related with Trait Anxiety and Multisensory Integration.
Anxiety is associated with an exaggerated expectancy of harm, including overestimation of how likely a conditioned stimulus (CS+) predicts a harmful unconditioned stimulus (US). In the current study we tested whether anxiety-associated expectancy of harm increases primary sensory cortex (S1) activity on non-reinforced (i.e., no shock) CS+ trials. Twenty healthy volunteers completed a differential-tone trace conditioning task while undergoing fMRI, with shock delivered to the left hand. We found a positive correlation between trait anxiety and activity in right, but not left, S1 during CS+ versus CS- conditions. Right S1 activity also correlated with individual differences in both primary auditory cortices (A1) and amygdala activity. Lastly, a seed-based functional connectivity analysis demonstrated that trial-wise S1 activity was positively correlated with regions of dorsolateral prefrontal cortex (dlPFC), suggesting that higher-order cognitive processes contribute to the anticipatory sensory reactivity. Our findings indicate that individual differences in trait anxiety relate to anticipatory reactivity for the US during associative learning. This anticipatory reactivity is also integrated along with emotion-related sensory signals into a brain network implicated in fear-conditioned responding.


Breaking up sitting with short frequent or long infrequent physical activity breaks does not lead to compensatory changes in appetite, appetite-regulating hormones or energy intake.
The aim of this study was to determine the appetite-related responses to breaking up prolonged sitting with physical activity bouts differing in frequency and duration among adult females. Fourteen sedentary females aged 34 ± 13 years with a body mass index of 27.1 ± 6.3 kg/m2 (mean ± SD) took part in a randomised crossover trial with three, 7.5 h conditions: (1) uninterrupted sitting (SIT), (2) sitting with short frequent 2-min moderate-intensity walking breaks every 30 min (SHORT-BREAKS), and (3) sitting with longer duration, less frequent 10-min moderate-intensity walking breaks every 170-180 min (LONG-BREAKS). The intensity and total duration of physical activity was matched between the SHORT-BREAKS and LONG-BREAKS conditions. Linear mixed models were used to compare the outcomes between conditions with significance being accepted as p ≤ 0.05. There were no significant between-condition differences in hunger, satisfaction, prospective food consumption or overall appetite area under the curve (AUC) (all p ≥ 0.801). Absolute ad libitum energy intake and relative energy intake (REI) did not differ significantly between conditions (all p ≥ 0.420). Acylated ghrelin and total peptide YY incremental and total AUC did not differ significantly between conditions (all p ≥ 0.388). Yet, there was a medium effect size for the higher acylated ghrelin incremental AUC in SHORT-BREAKS versus SIT (d = 0.61); the reverse was seen for total AUC, which was lower in SHORT-BREAKS versus SIT (d = 0.69). These findings suggest that breaking up sitting does not lead to compensatory changes in appetite, appetite hormones or energy intake regardless of physical activity bout duration and frequency among adult females.


Reference birth weight, length, chest circumference, and head circumference by gestational age in Japanese twins.
Numerous birth weight standards for twins have been reported in western countries, whereas little is in Japan. The aim of this study is to present birth weight, birth length, chest circumference, and head circumference references, clarifying features related to these body size parameters, and to compare our birth weight references with recent report of birth weight norms of Japanese twins using the vital statistics. The subjects consisted of 1,061 twin pairs in total, with birth years ranging from 1968 through 1990. Data was obtained from the Twins Protocol Questionnaire, which asked for information about twins' growth and development in infancy, and the "Maternal and Child Health Handbook," which was presented by Ministry of Health and Welfare. Statistical means, standard deviations, and selected percentiles by gestational age were calculated and smoothed using data that contained at least gestational age and one of the four items. Birth weight was significantly lighter than that of singletons when three additional parameters, especially chest and head circumference, were not measured. Gestational age was correlated with weight, length, chest circumference, and head circumference, in that order, for both sexes. Compared with singletons, birth weight difference in twins was marked and slight difference was observed as to length, whereas no difference was observed as to chest and head circumference. The present results as to birth weight were consistently similar to the birth weight norms of twins using vital statistics in Japan. Growth standards for twins, especially as to birth weight, are essential to understand and evaluate intrauterine growth of twins.


Psychosocial consequences of nasal aesthetic and functional surgery: a controlled prospective study in an ENT setting.
Much still needs to be known about what motivates and goes through patients' minds when undergoing nasal aesthetic surgery. Little is also known on how the aesthetic change affects the way other people see those patients after surgery, and if the improved appearance significantly benefits the patients' psychosocial functioning. So far, research has largely focused on subjects in Plastic Surgery settings, neglecting to investigate the specificities of rhinoplasty as performed by otolaryngologists. In order to elucidate these, a prospective controlled-study design was developed. Twenty-five consecutive patients, selected from an ENT practice for septorhinoplasty, were enrolled. They were submitted to pre-operative psychiatric interviews and psychological tests. Two control groups were simultaneously enlisted, and were submitted also to the same tests. Four to seven months after surgery, the septorhinoplasty patients were again evaluated by psychiatric interviews and psychological tests as well as asked to fill out a questionnaire addressing subjective satisfaction with the surgical results. They also underwent, at that time, a rhinomanometric examination assessing the objective success of surgery on nasal function. It was concluded that the study population was basically a psychologically well balanced group of patients, and that a successful surgical result could indeed, in some, improve pre-operative psychological "suffering" related to the nasal deformity, and give these patients a new social identity. Ultimately, it was found that the meeting of aesthetic requirements, frequently not put forward by the patient preoperatively, was the single most important factor required for a final complete satisfaction with the overall surgical results in this population.


Genotypic effects on norepinephrine-induced changes in thermogenesis, metabolic hormones, and metabolites in newborn calves.
Heat production was measured in newborn Angus-, Brahman-, and Tuli-sired calves born to Angus (n = 20) and Brahman (n = 26) dams, before (thermoneutral metabolic rate, TMR) and after norepinephrine (NE) infusion (peak metabolic rate, PMR), to assess genotypic effects on nonshivering thermogenesis in brown adipose tissue. Calves were fed pooled colostrum, fitted with jugular catheters, and placed in a temperature-controlled (37 degrees C) water immersion system. Heat production, determined by indirect calorimetry, and tympanic temperature were measured continuously in calves from approximately 3 to 6 h of age. Blood samples were collected at birth and at 0, 5, 20, 40, 60, 80, 100, and 120 min relative to NE infusion (35 micrograms.min-1.kg BW-1 for 4 min), and plasma was analyzed for metabolites (glucose, NEFA, and urea nitrogen [PUN]) and hormones (cortisol, triiodothyronine [T3] and thyroxine [T4]). Weight-specific TMR (cal.min-1.kg-1) was not affected by breed of sire or dam, although weight-specific PMR (cal.min-1.kg-1) was lower (P < .01) in Brahman-sired calves than in Angus- or Tuli-sired calves and was lower (P < .001) in calves born to Brahman rather than Angus dams. The reduction in weight-specific PMR due to the maternal Brahman influence was sire-breed dependent, and the reduction was largest (P < .01) for Tuli-sired (34.3%), intermediate (P < .05) for Brahman-sired (15.1%), and lowest (P > .25) for Angus-sired calves (4.1%). The PMR:TMR ratio was 1.80 and 2.21 +/- .06 in calves born to Brahman and Angus dams, respectively. Peak tympanic temperature was .6 degree C lower (P < .01) in calves born to Brahman rather than Angus dams. At birth, plasma NEFA concentrations were higher (P < .001) and glucose tended (P = .13) to be higher in calves born to Brahman rather than Angus dams. Cortisol, T3, and T4 concentrations at birth were higher in calves born to Brahman dams than in those born to Angus dams. These results suggest that calves born to Brahman dams may have less thermogenically active brown adipose tissue than calves born to Angus dams, which may contribute to the relative cold intolerance of calves with Bos indicus inheritance.


Two-factor theory, the actor-critic model, and conditioned avoidance.
Two-factor theory (Mowrer, 1947, 1951, 1956) remains one of the most influential theories of avoidance, but it is at odds with empirical findings that demonstrate sustained avoidance responding in situations in which the theory predicts that the response should extinguish. This article shows that the well-known actor-critic model seamlessly addresses the problems with two-factor theory, while simultaneously being consistent with the core ideas that underlie that theory. More specifically, the article shows that (1) the actor-critic model bears striking similarities to two-factor theory and explains all of the empirical phenomena that two-factor theory explains, in much the same way, and (2) there are subtle but important differences between the actor-critic model and two-factor theory, which result in the actor-critic model predicting the persistence of avoidance responses that is found empirically.


MiR-145 expression accelerates esophageal adenocarcinoma progression by enhancing cell invasion and anoikis resistance.
Carcinoma of the esophagus has a high case fatality ratio and is now the 6th most common cause of cancer deaths in the world. We previously conducted a study to profile the expression of miRNAs in esophageal adenocarcinoma (EAC) pre and post induction therapy. Of the miRNAs differentially expressed post induction chemoradiation, miR-145, a known tumor suppressor miRNA, was upregulated 8-fold following induction therapy, however, its expression was associated with shorter disease-free survival. This unexpected result was explored in this current study. In order to study the role of miR-145 in EAC, miRNA-145 was overexpressed in 3 EAC cell lines (OE33, FLO-1, SK-GT-4) and one ESCC cell line (KYSE-410). After validation of the expression of miR-145, hallmarks of cancer such as cell proliferation, resistance to chemotherapy drugs or anoikis, and cell invasion were analyzed. There were no differences in cell proliferation and 5 FU resistance between miR145 cell lines and the control cell lines. miR-145 expression also had no effect on cisplatin resistance in two of three cell lines (OE33 and FLO-1), but miR-145 appeared to protect SK-GT-4 cells against cisplatin treatment. However, there was a significant difference in cell invasion, cell adhesion and resistance to anoikis. All three EAC miR-145 cell lines invaded more than their respective controls. Similarly, OE33 and SK-GT-4 miR-145 cell lines were able to survive longer in a suspension state. While expression of miR-145 in ESCC stopped proliferation and invasion, expression of miR-145 in EAC cells enhanced invasion and anoikis resistance. Although more work is required to understand how miR-145 conveys these effects, expression of miR-145 appears to promote EAC progression by enhancing invasion and protection against anoikis, which could in turn facilitate distant metastasis.


Responses to Predictable versus Random Temporally Complex Stimuli from Single Units in Auditory Thalamus: Impact of Aging and Anesthesia.
Human aging studies suggest that an increased use of top-down knowledge-based resources would compensate for degraded upstream acoustic information to accurately identify important temporally rich signals. Sinusoidal amplitude-modulated (SAM) stimuli have been used to mimic the fast-changing temporal features in speech and species-specific vocalizations. Single units were recorded from auditory thalamus [medial geniculate body (MGB)] of young awake, aged awake, young anesthetized, and aged anesthetized rats. SAM stimuli were modulated between 2 and 1024 Hz with the modulation frequency (fm) changed randomly (RAN) across trials or sequentially (SEQ) after several repeated trials. Units were found to be RAN-preferring, SEQ-preferring, or nonselective based on total firing rate. Significant anesthesia and age effects were found. The majority (86%) of young anesthetized units preferred RAN SAM stimuli; significantly fewer young awake units (51%, p < 0.0001) preferred RAN SAM signals with 16% preferring SEQ SAM. Compared with young awake units, there was a significant increase of aged awake units preferring SEQ SAM (30%, p < 0.05). We examined RAN versus SEQ differences across fms by measuring selective fm areas under the rate modulation transfer function curve. The largest age-related differences from awake animals were found for mid-to-high fms in MGB units, with young units preferring RAN SAM while aged units showed a greater preference for SEQ-presented SAM. Together, these findings suggest that aged MGB units/animals employ increased top-down mediated stimulus context to enhance processing of "expected" temporally rich stimuli, especially at more challenging higher fms. Older individuals compensate for impaired ascending acoustic information by increasing use of cortical cognitive and attentional resources. The interplay between ascending and descending influences in the thalamus may serve to enhance the salience of speech signals that are degraded as they ascend to the cortex. The present findings demonstrate that medial geniculate body units from awake rats show an age-related preference for predictable modulated signals relative to randomly presented signals, especially at higher, more challenging modulation frequencies. Conversely, units from anesthetized animals, with little top-down influences, strongly preferred randomly presented modulated sequences. These results suggest a neuronal substrate for an age-related increase in experience/attentional-based influences in processing temporally complex auditory information in the auditory thalamus.


SUMOylation of the polyglutamine repeat protein, ataxin-1, is dependent on a functional nuclear localization signal.
SUMO (small ubiquitin-like modifier) is a member of the ubiquitin family of proteins. SUMO targets include proteins involved in numerous roles including nuclear transport and transcriptional regulation. The previous finding that mutant ataxin-1[82Q] disrupted promyelocytic leukemia (PML) oncogenic domains prompted us to determine whether ataxin-1 disrupts another component of PML oncogenic domains, Sp100 (100-kDa Speckled protein). Similar to the PML protein, mutant ataxin-1[82Q] redistributed Sp100 to mutant ataxin-1[82Q] nuclear inclusions. Based on the ability of PML and Sp100 to be covalently modified by SUMO, we investigated the ability of ataxin-1 to be SUMOylated. SUMO-1 was found to covalently modify the polyglutamine repeat protein ataxin-1. There was a decrease in ataxin-1 SUMOylation in the presence of the expanded polyglutamine tract, ataxin-1[82Q]. The phospho-mutant, ataxin-1[82Q]-S776A, restored SUMO levels to those of wild-type ataxin-1[30Q]. SUMOylation of ataxin-1 was dependent on a functional nuclear localization signal. Ataxin-1 SUMOylation was mapped to at least five lysine residues. Lys(16), Lys(194) preceding the polyglutamine tract, Lys(610)/Lys(697) in the C-terminal ataxin high mobility group domain, and Lys(746) all contribute to ataxin-1 SUMOylation.


An entirely automated method to score DSS-induced colitis in mice by digital image analysis of pathology slides.
The DSS (dextran sulfate sodium) model of colitis is a mouse model of inflammatory bowel disease. Microscopic symptoms include loss of crypt cells from the gut lining and infiltration of inflammatory cells into the colon. An experienced pathologist requires several hours per study to score histological changes in selected regions of the mouse gut. In order to increase the efficiency of scoring, Definiens Developer software was used to devise an entirely automated method to quantify histological changes in the whole H&E slide. When the algorithm was applied to slides from historical drug-discovery studies, automated scores classified 88% of drug candidates in the same way as pathologists' scores. In addition, another automated image analysis method was developed to quantify colon-infiltrating macrophages, neutrophils, B cells and T cells in immunohistochemical stains of serial sections of the H&E slides. The timing of neutrophil and macrophage infiltration had the highest correlation to pathological changes, whereas T and B cell infiltration occurred later. Thus, automated image analysis enables quantitative comparisons between tissue morphology changes and cell-infiltration dynamics.


Climate Change Adaptation through the Water-Energy-Food Nexus in Southern Africa.
Climate change is a complex and cross-cutting problem that needs an integrated and transformative systems approach to respond to the challenge. Current sectoral approaches to climate change adaptation initiatives often create imbalances and retard sustainable development. Regional and international literature on climate change adaptation opportunities and challenges applicable to southern Africa from a water-energy-food (WEF) nexus perspective was reviewed. Specifically, this review highlights climate change impacts on water, energy, and food resources in southern Africa, while exploring mitigation and adaptation opportunities. The review further recommends strategies to develop cross-sectoral sustainable measures aimed at building resilient communities. Regional WEF nexus related institutions and legal frameworks were also reviewed to relate the WEF nexus to policy. Southern Africa is witnessing an increased frequency and intensity in climate change-associated extreme weather events, causing water, food, and energy insecurity. A projected reduction of 20% in annual rainfall by 2080 in southern Africa will only increase the regional socio-economic challenges. This is exacerbating regional resource scarcities and vulnerabilities. It will also have direct and indirect impacts on nutrition, human well-being, and health. Reduced agricultural production, lack of access to clean water, sanitation, and clean, sustainable energy are the major areas of concern. The region is already experiencing an upsurge of vector borne diseases (malaria and dengue fever), and water and food-borne diseases (cholera and diarrhoea). What is clear is that climate change impacts are cross-sectoral and multidimensional, and therefore require cross-sectoral mitigation and adaptation approaches. In this regard, a well-coordinated and integrated WEF nexus approach offers opportunities to build resilient systems, harmonise interventions, and mitigate trade-offs and hence improve sustainability. This would be achieved through greater resource mobilisation and coordination, policy convergence across sectors, and targeting nexus points in the landscape. The WEF nexus approach has potential to increase the resilience of marginalised communities in southern Africa by contributing towards attaining the Sustainable Development Goals (SDGs 1, 2, 3, 6, 7, and 13).


Bone mass measurement by DXA: influence of analysis procedures and interunit variation.
Interunit variability among bone densitometers is due to different factors, including different calibration procedures and algorithms and variability in photon source energies and/or intensities. Other factors, such as the choice of scan parameters or the analysis procedures, can also introduce variability. The new generation of dual-energy x-ray absorptiometry (DXA) has partially improved this situation. The aim of this study was to investigate the operator-dependent analysis procedures that can affect scan results and to evaluate the phantom and in vivo interunit variation of some DXA instruments. Four DXA instruments (QDR 1000 and 1000/W, Hologic, Inc.) were used. Potential sources of variability in the analysis procedures of anteroposterior lumbar spine and hip scans were considered: in most cases these procedures significantly influenced scan results. On lumbar spine, an enlargement of the scan window of less than 3 cm was responsible for an average increase in bone mineral density (BMD) of about 3%. On the hip, lowering the scan window by about 1 cm accounted for an increase in the whole-segment BMD of about 4%. After standardization of analysis procedures, interunit and intraunit coefficients of variation and percentage differences among instruments were less than 1% for all the parameters considered (area and bone mineral content and density) with both an anatomic and a geometric phantom, and in nine subjects scanned by two different devices the percentage difference in BMD was greater than 2%. This study shows that present interunit variability allows comparisons among laboratories, but only if highly standardized analysis procedures are used.


Reverse Monte Carlo modeling of ion conducting network glasses: an evaluation based on molecular dynamics simulations.
We investigate the quality of structural models generated by the Reverse Monte Carlo (RMC) method in a typical application to glass systems. To this end we calculate diffraction data from a Li(2)O-SiO(2) molecular dynamics (MD) simulation and use it, in addition to minimal pair distances and coordination numbers of silicon (oxygen) to oxygen (silicon) ions, as input for RMC modeling. Then we compare partial radial distribution functions, coordination numbers, bond angles, and ring sizes predicted by the RMC models with those of the MD system. It is found that partial distribution functions and properties on small lengths scales, as distributions of coordination numbers and bond angles, are well reproduced by the RMC modeling. Properties in the medium-range order regime are, however, not well captured, as is demonstrated by comparison of ring size distributions. Due care therefore has to be exercised when extracting structural features from RMC models in this medium-range order regime. In particular we show that the occurrence of such features can be a mere consequence of the chosen starting configuration.


[Insights about the challenge of nursing education administration].
This article aims to trigger ideas and to point elements to for leaders' development to nursing education administration. While assuming the administrative role is necessary to understand the dimension of the educational process as something that goes beyond the simple knowledge transference. We present issues related to the nursing education dimensions, about the building a political pedagogical guideline to actions of professional development, based in the policies for the nursing curriculum. We mention the role of faculty leaders in the courses external and internal evaluation. We also present the need to redirect nurses' education to prepare them to respond properly (technically, scientifically and politically) to the workforce demand.


Spatiotemporal Dynamics of Vibrio cholerae in Turbid Alkaline Lakes as Determined by Quantitative PCR.
In recent years, global warming has led to a growing number of Vibrio cholerae infections in bathing water users in regions formerly unaffected by this pathogen. It is therefore of high importance to monitor V. cholerae in aquatic environments and to elucidate the main factors governing its prevalence and abundance. For this purpose, rapid and standardizable methods that can be performed by routine water laboratories are prerequisite. In this study, we applied a recently developed multiplex quantitative PCR (qPCR) strategy (i) to monitor the spatiotemporal variability of V. cholerae abundance in two small soda pools and a large lake that is intensively used for recreation and (ii) to elucidate the main factors driving V. cholerae dynamics in these environments. V. cholerae was detected with qPCR at high concentrations of up to 970,000 genomic units 100 ml-1 during the warm season, up to 2 orders of magnitude higher than values obtained by cultivation. An independent cytometric approach led to results comparable to qPCR data but with significantly more positive samples due to problems with DNA recovery for qPCR. Not a single sample was positive for toxigenic V. cholerae, indicating that only nontoxigenic V. cholerae (NTVC) was present. Temperature was the main predictor of NTVC abundance, but the quality and quantity of dissolved organic matter were also important environmental correlates. Based on this study, we recommend using the developed qPCR strategy for quantification of toxigenic and nontoxigenic V. cholerae in bathing waters with the need for improvements in DNA recovery.IMPORTANCE There is a definitive need for rapid and standardizable methods to quantify waterborne bacterial pathogens. Such methods have to be thoroughly tested for their applicability to environmental samples. In this study, we critically tested a recently developed multiplex qPCR strategy for its applicability to determine the spatiotemporal variability of V. cholerae abundance in lakes with a challenging water matrix. Several qPCR protocols for V. cholerae detection have been developed in the laboratory, but comprehensive studies on the application to environmental samples are extremely scarce. In our study, we demonstrate that our developed qPCR approach is a valuable tool but that there is a need for improvement in DNA recovery for complex water matrices. Furthermore, we found that nontoxigenic V. cholerae is present in very high numbers in the investigated ecosystems, while toxigenic V. cholerae is apparently absent. Such information is of importance for public health.


Anti-diabetic medications and risk of pancreatic cancer in patients with diabetes mellitus: a systematic review and meta-analysis.
Several preclinical and observational studies have shown that anti-diabetic medications (ADMs) may modify the risk of pancreatic cancer (PaC). We performed a systematic review and meta-analysis evaluating the effect of metformin, sulfonylureas (SUs), thiazolidinediones (TZDs), and insulin on the risk of PaC in patients with diabetes mellitus (DM). We conducted a systematic search of Medline, EMBASE, and Web of Science, up to June 2012, and published abstracts from major gastroenterology and oncology meetings from 2003 to 2012. Studies were included if they (1) evaluated and clearly defined exposure to metformin, SU, TZDs, and/or insulin, (2) reported PaC outcomes in patients with DM and (3) reported relative risks or odds ratio (OR) or provided data for their estimation. Summary OR estimates with 95% confidence intervals (CIs) were estimated using the random-effects model. Eleven studies (6 cohort, 3 case-control, and 2 randomized controlled trials (RCTs)) reported 1770 cases of PaC in 730,664 patients with DM. Meta-analysis of observational studies showed no significant association between metformin (n=9 studies; adjusted OR 0.76, 95% CI 0.57-1.03, P=0.073), insulin (n=7 studies; adjusted OR 1.59, 95% CI 0.85-2.96, P=0.144), or TZD (n=4 studies; adjusted OR 1.02, 95% CI 0.81-1.30, P=0.844) use and risk of developing PaC. Use of SU was associated with a 70% increase in the odds of PaC (n=8 studies; adjusted OR 1.70, 95% CI 1.27-2.28, P<0.001). There was considerable inherent heterogeneity between studies not explained by study design, setting, or comparator drug and is likely related to confounding by indication and reverse causality. The pooled analyses of the two RCTs were underpowered and provided non-significant results with wide, non-informative 95% CIs. Although SU seems to be associated with increased risk of PaC, meta-analysis of existing studies does not support a protective or harmful association between ADM use and risk of PaC in patients with DM. There was considerable heterogeneity across studies, and future, well-designed, prospective studies would be required to understand this association better.


Experience of a public education programme on early detection of cutaneous malignant melanoma.
A public education campaign is described which aimed at encouraging earlier self recognition and thus treatment of cutaneous malignant melanoma. The unique aspect of this campaign was that the changes in the numbers of referrals of patients with melanomas and the changes in the hospital workload associated with this programme were quantified. In the calendar year of the campaign and the following year a statistically significant rise was seen in the percentage of thin melanomas with a good prognosis that were treated and a concomitant significant fall in the proportion of thick lesions with a poor prognosis.


Exogenously applied sodium nitroprusside alleviates nickel toxicity in maize by regulating antioxidant activities and defense-related gene expression.
Nickel (Ni) stress adversely affects plant growth and biomass accumulation, posturing severe menace to crop production and food security. The current study aimed to determine the putative role of sodium nitroprusside (SNP) in mitigating Ni-induced phytotoxicity and identify the underlying defense mechanisms in maize, which are poorly understood. Our findings showed that SNP significantly augmented plant growth, biomass, and photosynthesis-related attributes (Fv/Fm, Fm, qP ETR, and ΦPSII) through diminishing Ni uptake and translocation in root and shoot tissues of maize under Ni stress conditions. In parallel, exogenous SNP substantially relieved maize seedlings from Ni-induced stress by enhancing enzymatic (SOD, CAT, and GPX) and non-enzymatic (phenol and flavonoids) antioxidant defenses and reducing oxidative stress indicators (MDA and H2 O2 ). The results revealed that SNP treatment increased the content of organic osmolyte glycine betaine and the activity of GST, concomitantly with ATP and ionic exchange capacity (including Ca2+ -ATPase and Mg2+ -ATPase), advocating its sufficiency to promote plant growth and avert Ni-induced stress in maize plants. The only exception was the production of organic acids (citric, oxalic, malic, and formic acids), which was reduced as SNP treatment relieved maize seedlings from Ni-induced oxidative damage. The application of SNP also displayed higher expression of defense- and detoxifying-related genes than in control treatments. Together, our data highlighted the mechanism involved in the amelioration of Ni toxicity by SNP; thus, suggesting a potential role of SNP in mitigating the adverse effects of Ni-contaminated soils to boost growth and yield of crop plants, that is, maize.


Association of the Effectiveness of Eye Drop Self-instillation and Glaucoma Progression.
Among patients with glaucoma or ocular hypertension, ineffective self-instillation of eye drops was associated with an increased long-term risk of progression or advancement of treatment to incisional surgery. The purpose of this study was to evaluate the association between the efficacy of self-instillation of eye drops and long-term glaucoma outcomes. In a previous study, video recordings of eye drop self-instillation by patients with glaucoma or ocular hypertension were graded as effective or ineffective depending on whether the patient successfully instilled at least 1 drop on the right ocular surface. Glaucomatous progression was then retrospectively defined as retinal nerve fiber layer thinning as measured by either optical coherence tomography, visual field progression, or need for incisional glaucoma surgery as determined by a glaucoma specialist unaware of patient performance in the eye drop instillation study. Subjects with at least 2 follow-up optical coherence tomography or visual field studies were included in the current study. The original study enrolled 119 patients. Sufficient follow-up data were available for 101 patients. Eighty-eight patients (87.1%) were effective in eye drop instillation at baseline. Mean follow-up was 5.1 years, during which time 73 patients (72.3%) had progression or underwent incisional surgery in either eye. A significantly higher proportion of patients in the ineffective group met the criteria for progression or underwent incisional surgery (effective: 68.2%; ineffective: 100%; N=101; P=0.017, Fisher exact test). Kaplan-Meier survival analyses showed a significantly faster time to reaching an endpoint in the ineffective group (N=101; P=0.012, log-rank test). There was no difference in age, baseline intraocular pressure, or baseline retinal nerve fiber layer thickness between the groups. Ineffective self-installation of eye drops was associated with an increased risk of glaucoma progression or treatment advancement to incisional surgery.


Mother-infant transfer of anti-human papillomavirus (HPV) antibodies following vaccination with the quadrivalent HPV (type 6/11/16/18) virus-like particle vaccine.
The exploratory immunogenicity objective of this analysis was to characterize the titer of vaccine human papillomavirus (HPV)-type immunoglobulins in both peripartum maternal blood and the cord blood of infants born to women who received blinded therapy. Data were derived from a randomized, placebo-controlled, double-blind safety, immunogenicity, and efficacy study (protocol 019; NCT00090220). This study enrolled 3,819 women between the ages of 24 and 45 years from 38 international study sites between 18 June 2004 and 30 April 2005. Data in the current analysis are from subjects enrolled in Philippines and Thailand. For each of HPV types 6, 11, 16, and 18, maternal anti-HPV was found in cord blood samples. Furthermore, HPV titers in cord blood samples were highly positively correlated with maternal HPV titers. Additionally, there were instances when anti-HPV antibodies were no longer detectable in maternal serum samples and yet were detected in matched cord blood samples. These results demonstrate that quadrivalent HPV (qHPV) vaccine-induced antibodies cross the placenta and could potentially provide some benefit against vaccine-type HPV infection and related diseases such as recurrent respiratory papillomatosis.


Microbial survivors: thermophiles, halophiles, and other prodigies.
When biologists encounter microbes flourishing in boiling water and other extreme habitats, they often consider such creatures as merely odd, and only search for possible protective mechanisms. But it may also be that extreme habitats resemble those where life first occurred, and that such organisms provide links with earlier evolution.


[Infant botulism and sudden infant death syndrome].
Infant botulism represents a distinct entity of botulism. Ingestion of the ubiquitously present spores of Clostridium botulinum leads to germination of the organism and neurotoxin production in the infant intestine. Symptoms typically develop gradually in contrast to classical food botulism in which an acute onset of symptoms shortly after the ingestion of preformed toxin in a food is characteristic. Microbiologically, the diagnosis is established by identification of Clostridium botulinum organism and toxin in stool specimen. However, positive results in these tests provide only indirect evidence for the clinical relevance of the neurotoxin since asymptomatic carriers have been found. The toxin irreversibly blocks the release of acetylcholin from the motoric end plate which results in muscle weakness and paralysis. Depending on the amount of toxin produced, infant botulism exhibits a broad clinical spectrum ranging from oligosymptomatic forms to a fulminant course with acute respiratory failure within hours leading to sudden death. Unrecognized mild forms or beginning muscle weakness can be a co-factor for other risk factors of sudden infant death (SIDS). In studies analyzing infants who died from SIDS, botulism bacteria or toxin were found in up to 20 % of cases. Infant botulism therefore represents an important differential diagnosis of unexplained and inconclusive muscular hypotonia in the first year of life.


Vitamin C and smoke inhalation injury.
A second potential therapeutic option for the parenchymal damage caused by inhalation injury is systemic administration of intravenous agents. The unique nature of the effects of the burn and smoke on lung physiology and immunology create new opportunities for systemic treatments targeting specific aspects of the response to injury. In addition, systemic therapies could be either isolated or combined with inhalation therapies to achieve optimal clinical response. The two articles in this section of the compendium address different, yet promising, systemic therapies: antithrombin and vitamin C.


Autoantibodies against galectins are associated with antiphospholipid syndrome in patients with systemic lupus erythematosus.
The presence of autoantibodies against immunoregulatory effectors can be relevant for onset and/or the progression of autoimmune disease. Emerging insights into an immunological activity profile including a role as opsonins give reason to systematically monitor sera of patients for immunoglobulin G (IgG) autoantibodies, preferably for several galectins at the same time. Here, we report on a study of chronic inflammatory rheumatic diseases, i.e. systemic lupus erythematosus (SLE; pilot cohort p, n = 40; confirmation cohort c, n = 109), rheumatoid arthritis (RA; p, n = 32; c, n = 25) and primary antiphospholipid syndrome (APS; c, n = 64). Enzyme-linked immunosorbent assay-based series using galectin-1, -2, -3, -4, -7, -8 and -9 and natural processing products, i.e. the truncated version of galectin-3 and the N-terminal domains of galectin-4, -8 and -9, were performed. Normal healthy donors (p, n = 20; c, n = 21) and patients with paraproteins (c, n = 19) served as controls. Highly significant optical density-value readings for IgG autoantibodies were consistently detected for the proto-type galectin-7 (SLE) and the tandem repeat-type galectin-8 and -9 (SLE and RA). Their presence was independent from the autoantibody status against double-stranded DNA (for patients with SLE) or a rheumatoid factor (for patients with RA), respectively. Importantly, anti-galectin-2 autoantibodies highly significantly correlated with the appearance of a secondary APS in patients with SLE so that this parameter may serve as an additional biomarker for APS. Equally of note, the presence of IgG autoantibodies against galectins capable to act as an opsonin may contribute to a sustained immune dysregulation in patients with chronic inflammatory rheumatic diseases.