In vivo optical investigation of short term skin water contact and moisturizer application using NIR spectroscopy.
Nowadays, a number of noninvasive methods and instruments are available to inspect the biophysical properties and effects of various applicants on human skin, providing quantitative measurements and more details regarding the interactions between skin and various products. Such methods include Near Infrared Spectroscopy (NIRS), a technique which over the years, has gained quite a reputation in being able to accurately determine moisture levels and water contents due to its sensitivity to hydrogen bonding. This paper reports preliminary results of an in vivo study carried out on the skin of a small number of human participants, investigating the optical response of human skin after direct short-term contact with water followed by application of a moisturizer, using a highly advanced spectrophotometer in the region of 900-2100 nm, and equipped with a reflectance fibre optic probe. Results obtained here certainly raise some questions regarding the optical characteristics of different skin types and the influence of frequent moisturizer use, as well as the varying response between different water bands in the NIR region. Future work will focus on gaining more knowledge about these, in order to further improve optical skin measurements, and hopefully support the design and development of a portable and/or miniaturized optical device that could provide reliable, accurate and fast skin hydration readings in real time.


Automated analysis of protein subcellular location in time series images.
Image analysis, machine learning and statistical modeling have become well established for the automatic recognition and comparison of the subcellular locations of proteins in microscope images. By using a comprehensive set of features describing static images, major subcellular patterns can be distinguished with near perfect accuracy. We now extend this work to time series images, which contain both spatial and temporal information. The goal is to use temporal features to improve recognition of protein patterns that are not fully distinguishable by their static features alone. We have adopted and designed five sets of features for capturing temporal behavior in 2D time series images, based on object tracking, temporal texture, normal flow, Fourier transforms and autoregression. Classification accuracy on an image collection for 12 fluorescently tagged proteins was increased when temporal features were used in addition to static features. Temporal texture, normal flow and Fourier transform features were most effective at increasing classification accuracy. We therefore extended these three feature sets to 3D time series images, but observed no significant improvement over results for 2D images. The methods for 2D and 3D temporal pattern analysis do not require segmentation of images into single cell regions, and are suitable for automated high-throughput microscopy applications. Images, source code and results will be available upon publication at http://murphylab.web.cmu.edu/software firstname.lastname@example.com.


The CURLY LEAF interacting protein BLISTER controls expression of polycomb-group target genes and cellular differentiation of Arabidopsis thaliana.
Polycomb-group (Pc-G) proteins are important regulators of many developmental processes in plants and animals and repress gene expression by imparting histone H3 lysine 27 trimethylation (H3K27me3). Here, we present the identification of the novel, plant-specific Arabidopsis thaliana protein BLISTER (BLI), which interacts with the Pc-G histone methyltransferase CURLY LEAF (CLF). We map the interaction of BLI with CLF to a predicted coiled-coil domain in BLI that shares similarity with STRUCTURAL MAINTENANCE OF CHROMOSOMES proteins. BLI colocalizes with CLF in the nucleus, shows an overlapping expression pattern with CLF throughout plant development that is strongest in dividing cells, and represses a subset of Pc-G target genes. Loss of BLI results in a pleiotropic developmental mutant phenotype, indicating that BLI prevents premature differentiation. Furthermore, bli mutants exhibit severe epidermal defects, including loss of cell adhesion, outgrowth of cells, and increased cotyledon cell size. As these phenotypes have not been observed in Pc-G mutants, we propose that BLI has functions related to Pc-G proteins but can also act independently in Arabidopsis development.


Occurrence and characterization of Shiga toxin-producing Escherichia coli in raw meat, raw milk, and street vended juices in Bangladesh.
The major objective of this study was to investigate the prevalence of Shiga toxin (Stx)-producing Escherichia coli (STEC) in different types of food samples and to compare their genetic relatedness with STEC strains previously isolated from animal sources in Bangladesh. We investigated a total of 213 food samples, including 90 raw meat samples collected from retail butcher shops, 20 raw milk samples from domestic cattle, and 103 fresh juice samples from street vendors in Dhaka city. We found that more than 68% (n = 62) of the raw meat samples were positive for the stx gene(s); 34% (n = 21) of buffalo meats and 66% (n = 41) of beef. Approximately 10% (n = 2) of the raw milk and 8% (n = 8) of the fresh juice samples were positive for stx. We isolated STEC O157 from seven meat samples (7.8%), of which two were from buffalo meats and five from beef; and no other STEC serotypes could be isolated. We could not isolate STEC from any of the stx-positive raw milk and juice samples. The STEC O157 isolates from raw meats were positive for the stx(2), eae, katP, etpD, and enterohemorrhagic E. coli hly virulence genes, and they belonged to three different phage types: 8 (14.3%), 31 (42.8%), and 32 (42.8%). Pulsed-field gel electrophoresis (PFGE) typing revealed six distinct patterns among seven isolates of STEC O157, suggesting a heterogeneous clonal diversity. Of the six PFGE patterns, one was identical and the other two were ≥90% related to PFGE patterns of STEC O157 strains previously isolated from animal feces, indicating that raw meats are readily contaminated with fecal materials. This study represents the first survey of STEC in the food chain in Bangladesh.


DNA damage in non-communicable diseases: A clinical and epidemiological perspective.
Non-communicable diseases (NCDs) are a leading cause of death and disability, representing 63% of the total death number worldwide. A characteristic phenotype of these diseases is the accelerated aging, which is the result of phenomena such as accumulated DNA damage, telomere capping loss and subcellular irreversible/nonrepaired oxidative damage. DNA damage, mostly oxidative, plays a key role in the development of most common NCDs. The present review will gather some of the most relevant knowledge concerning the presence of DNA damage in NCDs focusing on cardiovascular diseases, diabetes, chronic obstructive pulmonary disease, and neurodegenerative disorders, and discussing a selection of papers from the most informative literature. The challenge of comorbidity and the potential offered by new systems approaches for introducing these biomarkers into the clinical decision process will be discussed. Systems Medicine platforms represent the most suitable approach to personalized medicine, enabling to identify new patterns in the pathogenesis, diagnosis and prognosis of chronic diseases.


Psychiatric comorbidity and cognitive profile in children with narcolepsy with or without association to the H1N1 influenza vaccination.
To evaluate psychiatric comorbidity and the cognitive profile in children and adolescents with narcolepsy in western Sweden and the relationship of these problems to H1N1 vaccination. Thirty-eight patients were included in the study. We performed a population-based, cross-sectional study to investigate psychiatric comorbidity using a test battery of semistructured interviews generating Diagnostic and Statistical Manual of Mental Disorders, 4th Edition diagnoses, including the Development and Well-Being Assessment and the attention deficit hyperactivity disorder rating scale. The Autism Spectrum Screening Questionnaire and the Positive and Negative Syndrome Scale were used to screen for autistic traits and psychotic symptoms, respectively. The cognitive assessments were made by a clinical psychologist using the Wechsler Preschool and Primary Scale of Intelligence, Third Edition, the Wechsler Intelligence Scale for Children, Fourth Edition, or the Wechsler Adult Intelligence Scale, Fourth Edition. In the post-H1N1 vaccination (PHV) narcolepsy group (n = 31), 43% of patients had psychiatric comorbidity, 29% had attention deficit hyperactivity disorder (ADHD) inattentive type, 20% had major depression, 10% had general anxiety disorder, 7% had oppositional defiant disorder (ODD), 3% had pervasive developmental disorder not otherwise specified (i.e., atypical autism), and 3% had eating disorder not otherwise specified (anorectic type). In the non-post-H1N1 vaccination (nPHV) narcolepsy group, one of seven patients had ADHD, inattentive type and ODD. The most frequent psychiatric symptom was temper tantrums, which occurred in 94% of the patients in the PHV group and 71% of the patients in the nPHV narcolepsy group. The cognitive assessment profile was similar in both groups and showed normal results for mean full-scale IQ and perceptual speed but decreased verbal comprehension and working memory. Patients with psychiatric comorbidity had a significantly lower full-scale IQ compared to those without. Our study indicates increased psychiatric comorbidity in children and adolescents with narcolepsy. The identified cognitive profile with significantly lower verbal comprehension and working memory compared with the normal mean index could have important implications for social relations and schooling. The small numbers of patients with nPHV narcolepsy make it difficult to draw firm conclusions about the possible differences between the two groups of patients.


Antibodies targeting Clec9A promote strong humoral immunity without adjuvant in mice and non-human primates.
Targeting antigens to dendritic cell (DC) surface receptors using antibodies has been successfully used to generate strong immune responses and is currently in clinical trials for cancer immunotherapy. Whilst cancer immunotherapy focuses on the induction of CD8(+) T-cell responses, many successful vaccines to pathogens or their toxins utilize humoral immunity as the primary effector mechanism. Universally, these approaches have used adjuvants or pathogen material that augment humoral responses. However, adjuvants are associated with safety issues. One approach, successfully used in the mouse, to generate strong humoral responses in the absence of adjuvant is to target antigen to Clec9A, also known as DNGR-1, a receptor on CD8α(+) DCs. Here, we address two issues relating to clinical application. First, we address the issue of variable adjuvant-dependence for different antibodies targeting mouse Clec9A. We show that multiple sites on Clec9A can be successfully targeted, but that strong in vivo binding and provision of suitable helper T cell determinants was essential for efficacy. Second, we show that induction of humoral immunity to CLEC9A-targeted antigens is extremely effective in nonhuman primates, in an adjuvant-free setting. Our findings support extending this vaccination approach to humans and offer important insights into targeting design.


Syllable intelligibility for temporally filtered LPC cepstral trajectories.
The intelligibility of syllables whose cepstral trajectories were temporally filtered was measured. The speech signals were transformed to their LPC cepstral coefficients, and these coefficients were passed through different filters. These filtered trajectories were recombined with the residuals and the speech signal reconstructed. The intelligibility of the reconstructed speech segments was then measured in two perceptual experiments for Japanese syllables. The effect of various low-pass, high-pass, and bandpass filtering is reported, and the results summarized using a theoretical approach based on the independence of the contributions in different modulation bands. The overall results suggest that speech intelligibility is not severely impaired as long as the filtered spectral components have a rate of change between 1 and 16 Hz.


Trends of single-level anterior cervical discectomy and fusion documentation after the 2015 Centers for Medicare & Medicaid Services coding audit.
With the use of anterior cervical discectomy and fusion (ACDF) expected to rise by 13.3% from 2020 to 2040, the increased usage of interbody cages with integral anterior fixation prompted a Centers for Medicare & Medicaid Services (CMS) review, which resulted in coding changes affecting anterior instrumentation documentation. CMS determined that Current Procedural Terminology (CPT) code 22845 should not be used to report integrated instrumentation (plate) with an interbody device, and if additional anterior instrumentation (e.g., plates and screws) is placed with an integrated interbody device, then a 59 modifier should be used. There is sparse literature examining the trends of ACDF without and with additional anterior instrumentation after the 2015 CMS audit. Therefore, this study aimed to evaluate the trends of single-level subaxial ACDF utilization from 2011 to 2019 to determine whether the 2015 CMS audit influenced the documented usage of additional anterior instrumentation. A retrospective cohort study was performed using the commercially available database PearlDiver. Patient records were queried from 2011 to 2019 for single-level subaxial ACDF without (CPT code 22551) and with (CPT codes 22551 + 22845) instrumentation. Cochran-Armitage trend analyses were performed to evaluate the hypothesis that ACDF with additional anterior instrumentation decreased over the given time period. Between 2011 and 2019, the total number of single-level ACDFs decreased from 6202 to 4402. From 2011 to 2015, an average of 6240 patients per year underwent single-level subaxial ACDF; of those, 950 patients (15.2%) had ACDF without instrumentation and 5290 patients (84.8%) had ACDF with instrumentation. In 2016, the total number of single-level subaxial ACDFs decreased to 5525, with 1006 patients (18.2%) receiving no instrumentation and 4519 patients (81.8%) receiving instrumentation. From 2017 to 2019, an average of 4283 patients per year underwent a single-level subaxial ACDF; of these, 1280 (29.9%) had no instrumentation and 3003 (70.1%) had instrumentation (all p < 0.0001). From 2015 to 2019, single-level ACDF without instrumentation significantly increased by 91.5% and ACDF with anterior instrumentation significantly decreased by 18.1%. The 2015 CMS audit of interbody cages and anterior instrumentation coding (CPT code 22845) may account for the decreased documentation of anterior instrumentation in the 9-year period. Understanding CMS auditing could help surgeons perceive changes in practice patterns that may lead to a more thorough evaluation of patient outcomes, cost, and overall value.


Analysis of the role of the Pseudomonas syringae pv. syringae HrpZ harpin in elicitation of the hypersensitive response in tobacco using functionally non-polar hrpZ deletion mutations, truncated HrpZ fragments, and hrmA mutations.
Pseudomonas syringae pv. syringae, like many plant pathogenic bacteria, secretes a 'harpin' protein that can elicit the hypersensitive response (HR), a defensive cellular suicide, in non-host plants. The harpin-encoding hrpZ gene is located in an operon that also encodes Hrp secretion pathway components and is part of the functional cluster of hrp genes carried on cosmid pHIR11 that enables saprophytic bacteria like Escherichia coli and Pseudomonas fluorescens to elicit the HR in tobacco leaves. We have constructed functionally non-polar hrpZ deletion mutations, revealing that HrpZ is necessary for saprophytic bacteria carrying pHIR11 to elicit a typical HR, whereas it only enhances the elicitation activity of P. s. syringae. Partial deletion mutations revealed that the N-terminal 153 amino acids of HrpZ can enable E. coli MC4100-(pHIR11) to elicit a strong HR. hrpZ subclone products comprising the N-terminal 109 amino acids and C-terminal 216 amino acids, respectively, of the 341 amino acid protein were isolated and found to elicit the HR. P. fluorescens (pHIR11 hrmA::TnphoA) mutants do not elicit the HR, but cell fractionation and immunoblot analysis revealed that they produce and secrete wild-type levels of HrpZ. Therefore, elicitor activity resides in multiple regions of HrpZ, P. syringae produces elicitor(s) in addition to HrpZ, and HrpZ is essential but not sufficient for HR elicitation by saprophytic bacteria carrying pHIR11.


The costs and benefits of nonoperative management for adult scoliosis.
A prospective cohort of adult scoliosis patients treated nonoperatively had a minimum of 2-year follow-up during which time data were collected on the type and quantity of nonoperative treatment used. To quantify the use, cost, and effectiveness of nonoperative treatment for adult scoliosis. A 2007 systematic review of nonsurgical treatment in adult scoliosis revealed minimal data, and concluded that evidence for nonoperative care was lacking. Duration of use and frequency of visits were collected for 8 specific treatment methods: medication, physical therapy, exercise, injections/blocks, chiropractic care, pain management, bracing, and bed rest. Costs for each intervention were determined using the Medicare Fee schedule. Outcome measures were the SRS-22, SF-12, and ODI. Analysis was performed for the entire group, and for subsets of high (ODI, >40), mid (ODI = 21-40) and low (ODI, <or=20) symptom patients. A total of 123 patients (111 females, 12 males) with a mean age of 53.3 (18-79) years were evaluated. In 55 scoliosis patients who received no treatment, the only significant change in HRQOL measures over the 2-year period was in SRS satisfaction subscore (0.3 points, P = 0.014). Among the 68 adult scoliosis patients who used nonoperative resources, there was no significant change in any of the HRQOL outcome parameters. Mean treatment cost over the 2-year period was $10,815. Mean cost over the 2-year period averaged $9704 in the low symptom patients, $11,116 in the mid symptom, and $14,022 in the high symptom patients. This study questions the value of nonoperative treatment commonly used for adult scoliosis patients. Documented costs are substantial and no improvement in health status was observed. An important caveat is that treatment was not randomized and therefore the treatment group might have deteriorated if not for the treatment they received.


Social determinants of reproductive health in Morocco.
Moroccan population has known a growing demographic trend. However, beyond the global tendency, reproductive health remains characterised by inequalities and disparities between urban and rural, rich and poor, developed and deprived regions. In this study, we relied mainly on data and statistics provided by the last five censuses, the four Demographic Health Surveys, Multiple Indicator Cluster Surveys, reports of international bodies and publications dealing mainly with health and development in the Arab World. During the last decades, fertility declined due to different parameters. Infant mortality decreased and should reach the corresponding Millennium Development Goal whereas maternal mortality has stayed nearly constant. The achievements accomplished in reproductive health remain insufficient. Family planning and contraception policies need to reach more women; and antenatal and postnatal care should be enhanced especially towards poor women living in rural areas and deprived regions.


Fissure basalts and ocean-floor spreading on the East pacific rise.
A basalt pavement outcrops almost continuously in a band along the crestal region of the East Pacific Rise from about 14 degrees S to 6 degrees S, that is, for more than 800 ikilometers; the outcrop may well extend beyond the above limits along the axis of the rise. The basalt band is generally between 40 and 60 kilometers wide and is replaced laterally by sediment. The lavas are fresh, "oceanic tholeiites" which were emplaced less than I million years ago by fissure eruptions. These findings, can be explained by the hypothesis of ocean-floor spreading; the basalts are the expression of material originating from the mantle and rising through fissures along the axis of the ridge. The absence of an axial rift valley on the East Pacific Rise may be explained by the fact that large volumes of lava are being outpoured along its crest.


Safety evaluation of the food enzyme mannan endo-1,4-β-mannosidase from the genetically modified Trichoderma reesei strain RF6232.
The food enzyme mannan endo-1,4-β-mannosidase (1,4-β-d-mannan mannanohydrolase; EC 18.104.22.168) is produced with the genetically modified Trichoderma reesei strain RF6232 by AB Enzymes GmbH. The genetic modifications do not give rise to safety concerns. The food enzyme was considered free from viable cells of the production organism and recombinant DNA. It is intended to be used in coffee processing, fruit and vegetable processing for juice production and for edible oil production. Since residual amounts of total organic solids (TOS) are removed during refined edible oil production by repeated washing, dietary exposure was calculated only for the remaining two food manufacturing processes. Dietary exposure to the food enzyme-TOS was estimated to be up to 0.09 mg TOS/kg body weight (bw) per day in European populations. Genotoxicity tests did not raise a safety concern. The systemic toxicity was assessed by a repeated dose 90-day oral toxicity study in rats. The Panel identified a no observed adverse effect level of 100 mg TOS/kg bw per day, the lowest dose tested. This results in a margin of exposure above 1,100. A search for similarity of the amino acid sequence of the food enzyme to known allergens was made and one match was found. The Panel considered that, under the intended conditions of use, the risk of allergic sensitisation and elicitation reactions by dietary exposure cannot be excluded, in particular for individuals allergic to avocado, but the likelihood for this to occur is considered to be low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.


Complete Genome Sequences of Historic Clostridioides difficile Food-Dwelling Ribotype 078 Strains in Canada Identical to That of the Historic Human Clinical Strain M120 in the United Kingdom.
Clostridioides (Clostridium) difficile is a spore-forming anaerobic bacterium that causes severe intestinal diseases in humans. Here, we report the complete genome sequence of the first C. difficile foodborne type strain (PCR ribotype 078) isolated from food animals in Canada in 2004, which has 100% similarity to the genome sequence of the historic human clinical strain M120.


Exploring leadership in community nursing teams.
This article is a report on a study investigating how leadership is perceived in community nursing teams and how these perceptions are translated into working practices of team leaders. The consensus in community nursing literature is that leadership is important, and especially so in a time of change. However, little empirical evidence exists on how leadership works in practice. The study adopted an exploratory descriptive design, utilising individual semi-structured interviews and focus groups in four case-studies, with a total of 54 participants. Two case-studies focussed on district nursing teams and two involved public health nursing teams, located in two geographical areas. Participants debated their understanding of the concept of leadership, its associated practices and behaviours in teams, if they saw themselves as leaders, and what preparation was required. The study was undertaken in 2009. Framework analysis techniques were employed to analyse the data. A 'quasi-family' model of leadership emerged, with significant emphasis on the importance of personal relationships and support. Nursing grade had a greater impact on perceptions of leadership than geographical context or professional and clinical focus. No clear fit with any existing theoretical framework was identified. However, nurses in the highest grade banding, in particular, demonstrated practices associated with transformational leadership. Nurses expressed the very clear need to be acknowledged, respected and valued, and that those who provided this support were regarded as good leaders.


Pharmacological interventions for acute attacks of vestibular migraine.
Vestibular migraine is a form of migraine where one of the main features is recurrent attacks of vertigo. These episodes are often associated with other features of migraine, including headache and sensitivity to light or sound. The unpredictable and severe attacks of vertigo can lead to a considerable reduction in quality of life. The condition is estimated to affect just under 1% of the population, although many people remain undiagnosed. A number of pharmacological interventions have been used, or proposed to be used, at the time of a vestibular migraine attack to help reduce the severity or resolve the symptoms. These are predominantly based on treatments that are in use for headache migraine, with the belief that the underlying pathophysiology of these conditions is similar. OBJECTIVES: To assess the benefits and harms of pharmacological interventions used to relieve acute attacks of vestibular migraine. The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 23 September 2022. We included randomised controlled trials (RCTs) and quasi-RCTs in adults with definite or probable vestibular migraine comparing triptans, ergot alkaloids, dopamine antagonists, antihistamines, 5-HT3 receptor antagonists, gepants (CGRP receptor antagonists), magnesium, paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs) with either placebo or no treatment. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were: 1) improvement in vertigo (assessed as a dichotomous outcome - improved or not improved), 2) change in vertigo (assessed as a continuous outcome, with a score on a numerical scale) and 3) serious adverse events. Our secondary outcomes were: 4) disease-specific health-related quality of life, 5) improvement in headache, 6) improvement in other migrainous symptoms and 7) other adverse effects. We considered outcomes reported at three time points: < 2 hours, 2 to 12 hours, > 12 to 72 hours. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We included two RCTs with a total of 133 participants, both of which compared the use of triptans to placebo for an acute attack of vestibular migraine. One study was a parallel-group RCT (of 114 participants, 75% female). This compared the use of 10 mg rizatriptan to placebo. The second study was a smaller, cross-over RCT (of 19 participants, 70% female). This compared the use of 2.5 mg zolmitriptan to placebo. Triptans may result in little or no difference in the proportion of people whose vertigo improves at up to two hours after taking the medication. However, the evidence was very uncertain (risk ratio 0.84, 95% confidence interval 0.66 to 1.07; 2 studies; based on 262 attacks of vestibular migraine treated in 124 participants; very low-certainty evidence). We did not identify any evidence on the change in vertigo using a continuous scale. Only one of the studies assessed serious adverse events. No events were noted in either group, but as the sample size was small we cannot be sure if there are risks associated with taking triptans for this condition (0/75 receiving triptans, 0/39 receiving placebo; 1 study; 114 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: The evidence for interventions used to treat acute attacks of vestibular migraine is very sparse. We identified only two studies, both of which assessed the use of triptans. We rated all the evidence as very low-certainty, meaning that we have little confidence in the effect estimates and cannot be sure if triptans have any effect on the symptoms of vestibular migraine. Although we identified sparse information on potential harms of treatment in this review, the use of triptans for other conditions (such as headache migraine) is known to be associated with some adverse effects. We did not identify any placebo-controlled randomised trials for other interventions that may be used for this condition. Further research is needed to identify whether any interventions help to improve the symptoms of vestibular migraine attacks and to determine if there are side effects associated with their use.


Three cheers for the goblet cell: maintaining homeostasis in mucosal epithelia.
Many organs throughout the body maintain epithelial homeostasis by employing a mucosal barrier which acts as a lubricant and helps to preserve a near-sterile epithelium. Goblet cells are largely responsible for secreting components of this mucosal barrier and represent a major cellular component of the innate defense system. In this review we summarize what is known about the signaling pathways that control goblet cell differentiation in the intestine, the lung, and the ocular surface, and we discuss a novel functional role for goblet cells in mucosal epithelial immunology. We highlight the cell type-specificity of the circuitry regulating goblet cell differentiation and shed light on how changes to these pathways lead to altered goblet cell function, a prominent feature of mucosa-associated diseases.


Experimental autoimmune autonomic neuropathy.
Antibodies specific for the neuronal ganglionic nicotinic acetylcholine receptor (nAChR) are found in high titer in serum of patients with subacute autonomic failure. This clinical disorder is known as autoimmune autonomic neuropathy (AAN). Rabbits immunized with a neuronal nAChR alpha3 subunit fusion protein produce ganglionic nAChR antibodies and develop autonomic failure (experimental AAN, or EAAN). We used quantitative measures of autonomic function to demonstrate that this animal model of neuronal nAChR autoimmunity recapitulates the cardinal autonomic features of AAN in humans. The severity of dysautonomia in the rabbit ranges from isolated cardiovagal impairment to severe panautonomic failure with fixed mydriasis, gastroparesis, dry eyes, impaired heart rate variability, hypotension, and low plasma catecholamines. The severity of autonomic failure correlates with serum antibody levels. Immunohistochemical staining of superior cervical ganglia and myenteric plexus neurons demonstrates intact presynaptic nerve terminals and intact postsynaptic neurons containing cytoplasmic nAChR, but lacking surface nAChR. These findings define the autonomic physiology and histopathology of this novel animal model and support the concept that AAN in humans is a disorder of ganglionic cholinergic synaptic transmission caused by ganglionic nAChR antibodies.


Oil spill impacts on mangroves: Recommendations for operational planning and action based on a global review.
Mangrove tidal wetland habitats are recognised as highly vulnerable to large and chronic oil spills. This review of current literature and public databases covers the last 6 decades, summarising global data on oil spill incidents affecting, or likely to have affected, mangrove habitat. Over this period, there have been at least 238 notable oil spills along mangrove shorelines worldwide. In total, at least 5.5milliontonnes of oil has been released into mangrove-lined, coastal waters, oiling possibly up to around 1.94millionha of mangrove habitat, and killing at least 126,000ha of mangrove vegetation since 1958. However, there were assessment limitations with incomplete and unavailable data, as well as unequal coverage across world regions. To redress the gaps described here in reporting on oil spill impacts on mangroves and their recovery worldwide, a number of recommendations and suggestions are made for refreshing and updating standard operational procedures for responders, managers and researchers alike.


Monoclonal Antibodies, Derived from Humans Vaccinated with the RV144 HIV Vaccine Containing the HVEM Binding Domain of Herpes Simplex Virus (HSV) Glycoprotein D, Neutralize HSV Infection, Mediate Antibody-Dependent Cellular Cytotoxicity, and Protect Mice from Ocular Challenge with HSV-1.
The RV144 HIV vaccine trial included a recombinant HIV glycoprotein 120 (gp120) construct fused to a small portion of herpes simplex virus 1 (HSV-1) glycoprotein D (gD) so that the first 40 amino acids of gp120 were replaced by the signal sequence and the first 27 amino acids of the mature form of gD. This region of gD contains most of the binding site for HVEM, an HSV receptor important for virus infection of epithelial cells and lymphocytes. RV144 induced antibodies to HIV that were partially protective against infection, as well as antibodies to HSV. We derived monoclonal antibodies (MAbs) from peripheral blood B cells of recipients of the RV144 HIV vaccine and showed that these antibodies neutralized HSV-1 infection in cells expressing HVEM, but not the other major virus receptor, nectin-1. The MAbs mediated antibody-dependent cellular cytotoxicity (ADCC), and mice that received the MAbs and were then challenged by corneal inoculation with HSV-1 had reduced eye disease, shedding, and latent infection. To our knowledge, this is the first description of MAbs derived from human recipients of a vaccine that specifically target the HVEM binding site of gD. In summary, we found that monoclonal antibodies derived from humans vaccinated with the HVEM binding domain of HSV-1 gD (i) neutralized HSV-1 infection in a cell receptor-specific manner, (ii) mediated ADCC, and (iii) reduced ocular disease in virus-infected mice.IMPORTANCE Herpes simplex virus 1 (HSV-1) causes cold sores and neonatal herpes and is a leading cause of blindness. Despite many trials, no HSV vaccine has been approved. Nectin-1 and HVEM are the two major cellular receptors for HSV. These receptors are expressed at different levels in various tissues, and the role of each receptor in HSV pathogenesis is not well understood. We derived human monoclonal antibodies from persons who received the HIV RV144 vaccine that contained the HVEM binding domain of HSV-1 gD fused to HIV gp120. These antibodies were able to specifically neutralize HSV-1 infection in vitro via HVEM. Furthermore, we showed for the first time that HVEM-specific HSV-1 neutralizing antibodies protect mice from HSV-1 eye disease, indicating the critical role of HVEM in HSV-1 ocular infection.


Terminal fetal heart decelerations and neonatal outcomes.
To describe the incidence and characteristics of terminal fetal heart rate decelerations and to estimate their association with acidemia. A 5-year retrospective cohort study of all women with singleton, nonanomalous gestations who labored and reached complete dilation at or after 37 weeks of gestation. The 30 minutes of electronic fetal monitoring before delivery were interpreted by two formally trained research nurses, blind to clinical data, using American College of Obstetricians and Gynecologists guidelines. Terminal decelerations (decelerations without recovery of 120 seconds or more) defined the exposure. Terminal bradycardia (10 minutes or more) was secondarily explored. Univariable and multivariable analyses were performed to estimate risk of acidemia (umbilical cord gas arterial pH level 7.10 or less). Of 5,388 women meeting inclusion criteria, 951 (17.7%) experienced a terminal deceleration whereas 4,437 (82.3%) did not. The incidence of acidemia among the 951 women with a terminal deceleration was low (1.3%; n=12). However, acidemia (adjusted odds ratio [OR] 18.6; 95% confidence [CI] 5.0-68.9) and higher-level nursery admission (adjusted OR 5.4; 95% CI 1.9-15.3) were more likely if the terminal deceleration was 10 minutes or more. Terminal decelerations were longer among neonates with acidemia (6.7 minutes compared with 3.2 minutes; P<.01). For every additional 120 seconds of duration beyond the first 120 seconds, there was a corresponding decrease in umbilical cord gas pH level by 0.042 (95% CI 0.040-0.048; P<.01). More than 98% of term fetuses with terminal decelerations deliver with normal umbilical cord gas pH levels. However, bradycardia is associated with increased risk of acidemia and higher-level nursery admission. This information can be incorporated into clinical decision-making regarding urgency of delivery. II.


Assessment of FANCD2 nuclear foci formation in paraffin-embedded tumors: a potential patient-enrichment strategy for treatment with DNA interstrand crosslinking agents.
A major mechanism of DNA repair related to homologous recombination is the Fanconi anemia (FA) pathway. FA genes collaborate with BRCA genes to form foci of DNA repair on chromatin after DNA damage or during the S phase of the cell cycle. Our goal was to develop a method capable of evaluating the functional status of the pathway in patients' tumor tissue, which could also be practically incorporated into large-scale screening. To develop this method, we first used Western immunoblot to detect FANCD2 protein monoubiquitination in fresh tumor specimens of patients with ovarian cancer undergoing surgery and stained formalin-fixed paraffin-embedded tumor tissue simultaneously with 4',6-diamidino-2-phenylindole, FANCD2, and Ki67 antibodies, eventually extending this method to other solid tumors. This triple stain permitted evaluation of the presence, or lack thereof, of FANCD2 subnuclear repair foci in proliferating cells by immunofluorescence microscopy. Overall, we evaluated 156 formalin-fixed paraffin-embedded tumor samples using the FA triple-staining immunofluorescence method. The ratios of FANCD2 foci-negative tumors in ovarian, lung, and breast tumor samples were 21%, 20%, and 29.4%, respectively. Our studies have led to the development of a suitable method for screening, capable of identifying tumors with somatic functional defects in the FA pathway. The use of paraffin-embedded tissues renders the reported method suitable for large-scale screening to select patients for treatment with DNA interstrand crosslinking agents, poly ADP-ribose polymerase inhibitors, or their combination.


Progression of human breast cancer cells from hormone-dependent to hormone-independent growth both in vitro and in vivo.
We have isolated a series of sublines of the hormone-dependent MCF-7 human breast cancer cell line after selection both in vivo and in vitro for growth in the presence of subphysiological concentrations of estrogens. These sublines represent a model system for study of the processes leading to hormonal autonomy. The cells form growing tumors in ovariectomized athymic nude mice in the absence of estrogen supplementation but retain some responsivity to estrogen as determined by stimulation of the rate of tumor growth in vivo and by induction of progesterone receptor. An ovarian-independent but hormone-responsive phenotype may occur early in the natural progression to hormone-independent and unresponsive growth in breast cancer. We observed no change in the affinity or decrease in the level of expression of estrogen receptors and progesterone receptors among the sublines and the parental cells. Epidermal growth factor receptors are not overexpressed in ovarian-independent cells. Thus, altered hormone receptor expression may be a late event in the acquisition of a hormone-independent and unresponsive phenotype. Sublines isolated by in vivo but not in vitro selection are more invasive than the parental cells both in vivo and across an artificial basement membrane in vitro. Thus, as yet unknown tumor-host interactions may be important in the development of an invasive phenotype. Furthermore, acquisition of the ovarian-independent and invasive phenotypes can occur independently.


Barbiturate anesthetics inhibit thromboxane-, potassium-, but not angiotensin-induced pulmonary vasoconstriction.
Administration of the oxidant lipid peroxide tertiary butyl hydroperoxide (t-bu-OOH) in the isolated rabbit lung leads to acute pulmonary vasoconstriction, which is caused by the synthesis of thromboxane. The inhalational anesthetics, halothane, nitrous oxide, and cyclopropane, markedly enhance t-bu-OOH-induced pulmonary vasoconstriction and thromboxane production. The effects of the intravenous (iv) barbiturates thiopental and pentobarbital on t-bu-OOH-induced vasoconstriction were studied. Thiopental completely and pentobarbital partially blocked t-bu-OOH-induced vasoconstriction. Thiopental inhibited t-bu-OOH-induced synthesis of thromboxane and prostacyclin but pentobarbital did not. This inhibitory action of thiopental may be due to its antioxidant properties because similar inhibition has been observed of t-bu-OOH-induced thromboxane production with the antioxidants, vitamin E, or butylated hydroxylanisole. Thiopental and pentobarbital also inhibited the vasoconstriction induced by a thromboxane analog, epoxymethano prostaglandin H2 (U46619). Finally, both barbiturates partially inhibited the pulmonary vasoconstriction caused by potassium chloride, which requires calcium entry, but they did not inhibit the constriction caused by angiotensin II, which does not require calcium entry. These results suggest that pentobarbital and thiopental may block pulmonary vasoconstriction by inhibiting calcium entry.


Towards a culturally acceptable end-of-life survey questionnaire: a Bengali translation of VOICES.
To assess the cultural acceptability and appropriateness of an English end-of-life survey questionnaire translated into Bengali for use in east London. Group discussions with informal carers (n=3 groups) and professionals (n = l1 group). Informal carers within a Bengali-speaking community (n = 26) in east London participated in three groups discussions led by three community workers trained in interviewing procedures. These data were followed up with one group discussion with bilingual health and social care professionals (n = 6). Data subject to content analysis. Participants were supportive of the development of the translated questionnaire. However, attention should be paid to vocabulary, shared meanings, cultural equivalence and the ways people conceptualize health and illness, and death and dying. These findings, together with participants' views on the administration of the questionnaire, will prompt revisions to the research approach when targeting ethnic and cultural groups in the future.


The MRL Model: A Valuable Tool in Studies of Autoimmunity-Brain Interactions.
The link between systemic autoimmunity, brain pathology, and aberrant behavior is still a largely unexplored field of biomedical science. Accumulating evidence points to causal relationships between immune factors, neurodegeneration, and neuropsychiatric manifestations. By documenting autoimmunity-associated neuronal degeneration and cytotoxicity of the cerebrospinal fluid from disease-affected subjects, the murine MRL model had shown high validity in revealing principal pathogenic circuits. In addition, unlike any other autoimmune strain, MRL mice produce antibodies commonly found in patients suffering from lupus and other autoimmune disorders. This review highlights importance of the MRL model as a useful preparation in understanding the links between immune system and brain function.


Effect of U and 137Cs chronic contamination on dopamine and serotonin metabolism in the central nervous system of the rat.
Following the Chernobyl accident, the most significant problem for the population of the former Soviet Union for the next 50-70 years will be chronic internal contamination by radionuclides. One of the few experiments carried out in this field reported that neurotransmitter metabolism in the central nervous system of the rat was disturbed after feeding with oats contaminated by 137Cs for 1 month. The present study assessed the effect of chronic contamination by depleted U or 137Cs on the metabolism of two neurotransmitters in cerebral areas of rats. Dopamine and serotonin were chosen because their metabolism has been shown to be disturbed after external irradiation, even at moderate doses. Dopamine, serotonin, and some of their catabolites were measured by high-pressure liquid chromatography coupled with an electrochemical detector in five cerebral structures of rats contaminated over a 1-month period by drinking water (40 mg U.L -1 or 6500 Bq 137Cs.L -1). In the striatum, hippocampus, cerebral cortex, thalamus, and cerebellum, the dopamine, serotonin, and catabolite levels were not significantly different between the control rats and rats contaminated by U or 137Cs. These results are not in accordance with those previously described.


Inhibitory activity of the isoflavone biochanin A on intracellular bacteria of genus Chlamydia and initial development of a buccal formulation.
Given the established role of Chlamydia spp. as causative agents of both acute and chronic diseases, search for new antimicrobial agents against these intracellular bacteria is required to promote human health. Isoflavones are naturally occurring phytoestrogens, antioxidants and efflux pump inhibitors, but their therapeutic use is limited by poor water-solubility and intense first-pass metabolism. Here, we report on effects of isoflavones against C. pneumoniae and C. trachomatis and describe buccal permeability and initial formulation development for biochanin A. Biochanin A was the most potent Chlamydia growth inhibitor among the studied isoflavones, with an IC50 = 12 µM on C. pneumoniae inclusion counts and 6.5 µM on infectious progeny production, both determined by immunofluorescent staining of infected epithelial cell cultures. Encouraged by the permeation of biochanin A across porcine buccal mucosa without detectable metabolism, oromucosal film formulations were designed and prepared by a solvent casting method. The film formulations showed improved dissolution rate of biochanin A compared to powder or a physical mixture, presumably due to the solubilizing effect of hydrophilic additives and presence of biochanin A in amorphous state. In summary, biochanin A is a potent inhibitor of Chlamydia spp., and the in vitro dissolution results support the use of a buccal formulation to potentially improve its bioavailability in antichlamydial or other pharmaceutical applications.


Adaptive radiation within the vaccine target tetraspanin-23 across nine Schistosoma species from Africa.
High levels of polymorphism in DNA sequences of tetraspanin-23 (TSP-23) were revealed within and between nine different species of Schistosoma from Africa including Schistosoma mansoni, Schistosoma rodhaini, Schistosoma margrebowiei, Schistosoma mattheei, Schistosoma intercalatum, Schistosoma haematobium, Schistosoma guineensis, Schistosoma curassoni and Schistosoma bovis. The greatest levels of diversity coincided with evidence of positive selection (d(N)/d(S)>1) within regions that code for extracellular loops of TSP-23 believed to interact with the host immune system. Kolaskar and Tongaonkar antigenicity predictions of protein sequences were compared across species and high levels of variation in antigenicity were also identified with each species which possessed their own unique antigenic profile. Phylogenetic analysis of TSP-23 proteins suggested evidence of convergent evolution in antigenic lineages as no true inter-species phylogenetic relationships were seen. This could be indicative of host-specific evolution of antigens in different species of schistosomes, a factor that should be considered carefully when developing vaccine targets.


Wideband acoustic immittance measures: developmental characteristics (0 to 12 months).
Rapid developmental changes of the peripheral auditory system in normal infants occur in the first year of life. Specifically, the postnatal development of the external and middle ear affects all measures of external and middle ear function including wideband acoustic immittance(WAI). This article provides an overview of WAI studies in newborns and infants from a developmental perspective. Normative WAI data in newborns are fairly consistent across studies. However, there are discrepancies in some WAI measures between studies, possibly due to differences in sampling, methodology, and instrumentation. Accuracy of WAI measurements is compromised when a good probe seal cannot be maintained during testing or an inaccurate estimate of the cross-sectional area of the ear canal of newborns occurs. Comparison of WAI data between age groups from 0 to 12 months reveals maturation effects. Additional age-specific longitudinal and cross-sectional normative WAI data for infants from birth to 12 months are required to validate and consolidate existing data.


Analysis of common bean expressed sequence tags identifies sulfur metabolic pathways active in seed and sulfur-rich proteins highly expressed in the absence of phaseolin and major lectins.
A deficiency in phaseolin and phytohemagglutinin is associated with a near doubling of sulfur amino acid content in genetically related lines of common bean (Phaseolus vulgaris), particularly cysteine, elevated by 70%, and methionine, elevated by 10%. This mostly takes place at the expense of an abundant non-protein amino acid, S-methyl-cysteine. The deficiency in phaseolin and phytohemagglutinin is mainly compensated by increased levels of the 11S globulin legumin and residual lectins. Legumin, albumin-2, defensin and albumin-1 were previously identified as contributing to the increased sulfur amino acid content in the mutant line, on the basis of similarity to proteins from other legumes. Profiling of free amino acid in developing seeds of the BAT93 reference genotype revealed a biphasic accumulation of gamma-glutamyl-S-methyl-cysteine, the main soluble form of S-methyl-cysteine, with a lag phase occurring during storage protein accumulation. A collection of 30,147 expressed sequence tags (ESTs) was generated from four developmental stages, corresponding to distinct phases of gamma-glutamyl-S-methyl-cysteine accumulation, and covering the transitions to reserve accumulation and dessication. Analysis of gene ontology categories indicated the occurrence of multiple sulfur metabolic pathways, including all enzymatic activities responsible for sulfate assimilation, de novo cysteine and methionine biosynthesis. Integration of genomic and proteomic data enabled the identification and isolation of cDNAs coding for legumin, albumin-2, defensin D1 and albumin-1A and -B induced in the absence of phaseolin and phytohemagglutinin. Their deduced amino acid sequences have a higher content of cysteine than methionine, providing an explanation for the preferential increase of cysteine in the mutant line. The EST collection provides a foundation to further investigate sulfur metabolism and the differential accumulation of sulfur amino acids in seed of common bean. Identification of sulfur-rich proteins whose levels are elevated in seed lacking phaseolin and phytohemagglutinin and sulfur metabolic genes may assist the improvement of protein quality.


Adult dyslexic readers benefit less from visual input during audiovisual speech processing: fMRI evidence.
The aim of the present fMRI study was to investigate whether typical and dyslexic adult readers differed in the neural correlates of audiovisual speech processing. We tested for Blood Oxygen-Level Dependent (BOLD) activity differences between these two groups in a 1-back task, as they processed written (word, illegal consonant strings) and spoken (auditory, visual and audiovisual) stimuli. When processing written stimuli, dyslexic readers showed reduced activity in the supramarginal gyrus, a region suggested to play an important role in phonological processing, but only when they processed strings of consonants, not when they read words. During the speech perception tasks, dyslexic readers were only slower than typical readers in their behavioral responses in the visual speech condition. Additionally, dyslexic readers presented reduced neural activation in the auditory, the visual, and the audiovisual speech conditions. The groups also differed in terms of superadditivity, with dyslexic readers showing decreased neural activation in the regions of interest. An additional analysis focusing on vision-related processing during the audiovisual condition showed diminished activation for the dyslexic readers in a fusiform gyrus cluster. Our results thus suggest that there are differences in audiovisual speech processing between dyslexic and normal readers. These differences might be explained by difficulties in processing the unisensory components of audiovisual speech, more specifically, dyslexic readers may benefit less from visual information during audiovisual speech processing than typical readers. Given that visual speech processing supports the development of phonological skills fundamental in reading, differences in processing of visual speech could contribute to differences in reading ability between typical and dyslexic readers.


Linking management planning for coastal wetlands to potential future wave attenuation under a range of relative sea-level rise scenarios.
Understanding changes in wave attenuation by emergent vegetation as wetlands degrade or accrete over time is crucial for incorporation of wetlands into holistic coastal risk management. Linked SLAMM and XBeach models were used to investigate potential future changes in wave attenuation over a 50-year period in a degrading, subtropical wetland and a prograding, temperate wetland. These contrasting systems also have differing management contexts and were contrasted to demonstrate how the linked models can provide management-relevant insights. Morphological development of wetlands for different scenarios of sea-level rise and accretion was simulated with SLAMM and then coupled with different vegetation characteristics to predict the influence on future wave attenuation using XBeach. The geomorphological context, subsidence, and accretion resulted in large predicted reductions in the extent of vegetated land (e.g., wetland) and changes in wave height reduction potential across the wetland. These were exacerbated by increases in sea-level from +0.217 m to +0.386 m over a 50-year period, especially at the lowest accretion rates in the degrading wetland. Mangrove vegetation increased wave attenuation within the degrading, subtropical, saline wetland, while grazing reduced wave attenuation in the temperate, prograding wetland. Coastal management decisions and actions, related to coastal vegetation type and structure, have the potential to change future wave attenuation at a spatial scale relevant to coastal protection planning. Therefore, a coastal management approach that includes disaster risk reduction, biodiversity, and climate change, can be informed by coastal modeling tools, such as those demonstrated here for two contrasting case studies.


Clinical Trials With Mesenchymal Stem Cells: An Update.
In the last year, the promising features of mesenchymal stem cells (MSCs), including their regenerative properties and ability to differentiate into diverse cell lineages, have generated great interest among researchers whose work has offered intriguing perspectives on cell-based therapies for various diseases. Currently the most commonly used adult stem cells in regenerative medicine, MSCs, can be isolated from several tissues, exhibit a strong capacity for replication in vitro, and can differentiate into osteoblasts, chondrocytes, and adipocytes. However, heterogeneous procedures for isolating and cultivating MSCs among laboratories have prompted the International Society for Cellular Therapy (ISCT) to issue criteria for identifying unique populations of these cells. Consequently, the isolation of MSCs according to ISCT criteria has produced heterogeneous, nonclonal cultures of stromal cells containing stem cells with different multipotent properties, committed progenitors, and differentiated cells. Though the nature and functions of MSCs remain unclear, nonclonal stromal cultures obtained from bone marrow and other tissues currently serve as sources of putative MSCs for therapeutic purposes, and several findings underscore their effectiveness in treating different diseases. To date, 493 MSC-based clinical trials, either complete or ongoing, appear in the database of the US National Institutes of Health. In the present article, we provide a comprehensive review of MSC-based clinical trials conducted worldwide that scrutinizes biological properties of MSCs, elucidates recent clinical findings and clinical trial phases of investigation, highlights therapeutic effects of MSCs, and identifies principal criticisms of the use of these cells. In particular, we analyze clinical trials using MSCs for representative diseases, including hematological disease, graft-versus-host disease, organ transplantation, diabetes, inflammatory diseases, and diseases in the liver, kidney, and lung, as well as cardiovascular, bone and cartilage, neurological, and autoimmune diseases.


Time-of-Flight Microwave Camera.
Microwaves can penetrate many obstructions that are opaque at visible wavelengths, however microwave imaging is challenging due to resolution limits associated with relatively small apertures and unrecoverable "stealth" regions due to the specularity of most objects at microwave frequencies. We demonstrate a multispectral time-of-flight microwave imaging system which overcomes these challenges with a large passive aperture to improve lateral resolution, multiple illumination points with a data fusion method to reduce stealth regions, and a frequency modulated continuous wave (FMCW) receiver to achieve depth resolution. The camera captures images with a resolution of 1.5 degrees, multispectral images across the X frequency band (8 GHz-12 GHz), and a time resolution of 200 ps (6 cm optical path in free space). Images are taken of objects in free space as well as behind drywall and plywood. This architecture allows "camera-like" behavior from a microwave imaging system and is practical for imaging everyday objects in the microwave spectrum.


Over time, do anthropometric measures still predict diabetes incidence in chinese han nationality population from chengdu community?
Objective. To examine whether anthropometric measures could predict diabetes incidence in a Chinese population during a 15-year follow-up. Design and Methods. The data were collected in 1992 and then again in 2007 from the same group of 687 individuals. Waist circumference, body mass index, waist to hip ratio, and waist to height ratio were collected based on a standard protocol. To assess the effects of baseline anthropometric measures on the new onset of diabetes, Cox's proportional hazards regression models were used to estimate the hazard ratios of them, and the discriminatory power of anthropometric measures for diabetes was assessed by the area under the receiver operating curve (AROC). Results. Seventy-four individuals were diagnosed with diabetes during a 15-year follow-up period (incidence: 10.8%). These anthropometric measures also predicted future diabetes during a long follow-up (P < 0.001). At 7-8 years, the AROC of central obesity measures (WC, WHpR, WHtR) were higher than that of general obesity measures (BMI) (P < 0.05). But, there were no significant differences among the four anthropometric measurements at 15 years. Conclusions. These anthropometric measures could still predict diabetes with a long time follow-up. However, the validity of anthropometric measures to predict incident diabetes may change with time.


Efficacy of a multivalent modified-live virus vaccine containing a Mannheimia haemolytica toxoid in calves challenge exposed with Bibersteinia trehalosi.
To determine the efficacy of a multivalent modified-live virus (MLV) vaccine containing a Mannheimia haemolytica toxoid to reduce pneumonia and mortality rate when administered to calves challenge exposed with virulent Bibersteinia trehalosi. Animals-74 Holstein calves. Calves were assigned to 2 treatment groups. Calves in the control group (n = 36) were vaccinated by SC administration of 2 mL of a commercial 5-way MLV vaccine, and calves in the other group (38) were vaccinated by SC administration of a 2-mL dose of a 5-way MLV vaccine containing M haemolytica toxoid (day 0). On day 21, calves were transtracheally administered B trehalosi. Serum was obtained for analysis of antibody titers against M haemolytica leukotoxin. Nasopharyngeal swab specimens were collected from calves 1 day before vaccination (day -1) and challenge exposure (day 20) and cultured to detect bacterial respiratory pathogens. Clinical scores, rectal temperature, and death attributable to the challenge-exposure organism were recorded for 6 days after challenge exposure. Remaining calves were euthanized at the end of the study. Necropsy was performed on all calves, and lung lesion scores were recorded. Calves vaccinated with the MLV vaccine containing M haemolytica toxoid had significantly lower lung lesion scores, mortality rate, and clinical scores for respiratory disease, compared with results for control calves. Administration of a multivalent MLV vaccine containing M haemolytica toxoid protected calves against challenge exposure with virulent B trehalosi by reducing the mortality rate, lung lesion scores, and clinical scores for respiratory disease.


Thoracic surgical spectrum of HIV infection.
The thoracic surgeon is often called on to diagnose or treat a variety of disorders associated with human immunodeficiency virus (HIV) infection. Surgical mediastinal exploration through cervical and anterior approaches is a safe and valuable modality in appropriately selected patients with unexplained mediastinal lymphadenopathy. Open lung biopsy is used in a small subset of HIV-infected patients with undiagnosed diffuse or multifocal pulmonary disease, with an anticipated diagnostic yield of more than 70%. The biopsy can be performed either thoracoscopically or via thoracotomy, based on the expertise and discretion of the surgeon. Open lung biopsy should be used very selectively and in patients with bronchoscopically confirmed diagnoses who are failing optimal medical therapy, because the impact on outcome is minuscule and because open lung biopsy is best avoided altogether in patients with established respiratory failure. Patients with acquired immune deficiency syndrome (AIDS) have an increased incidence of pneumothorax, often associated with Pneumocystis carinii pneumonia. Depending on the clinical scenario, tube thoracostomy, pleurodesis, or pleurectomy may be used. Thoracic empyema in AIDS patients requires urgent intercostal drainage and close clinical surveillance to discern the need for decortication or rib resection and open drainage. A surgical approach to pyogenic lung abscess or invasive aspergillosis is occasionally useful. Although it is controversial whether the incidence of lung cancer is increased in patients with HIV infection, HIV-positive patients with early stage nonsmall-cell lung cancer who are otherwise surgical candidates should undergo resection, especially in the era of highly active antiretroviral therapy.


Role of the fatty acid binding protein mal1 in obesity and insulin resistance.
The metabolic syndrome is a cluster of metabolic and inflammatory abnormalities including obesity, insulin resistance, type 2 diabetes, hypertension, dyslipidemia, and atherosclerosis. The fatty acid binding proteins aP2 (fatty acid binding protein [FABP]-4) and mal1 (FABP5) are closely related and both are expressed in adipocytes. Previous studies in aP2-deficient mice have indicated a significant role for aP2 in obesity-related insulin resistance, type 2 diabetes, and atherosclerosis. However, the biological functions of mal1 are not known. Here, we report the generation of mice with targeted null mutations in the mal1 gene as well as transgenic mice overexpressing mal1 from the aP2 promoter/enhancer to address the role of this FABP in metabolic regulation in the presence or absence of obesity. To address the role of the second adipocyte FABP in metabolic regulation in the presence and deficiency of obesity, absence of mal1 resulted in increased systemic insulin sensitivity in two models of obesity and insulin resistance. Adipocytes isolated from mal1-deficient mice also exhibited enhanced insulin-stimulated glucose transport capacity. In contrast, mice expressing high levels of mal1 in adipose tissue display reduced systemic insulin sensitivity. Hence, our results demonstrate that mal1 modulates adipose tissue function and contributes to systemic glucose metabolism and constitutes a potential therapeutic target in insulin resistance.


Vitamin D receptor signaling in podocytes protects against diabetic nephropathy.
Vitamin D and its analogs have antiproteinuric activity and podocytes express the vitamin D receptor, but whether vitamin D signaling in podocytes accounts for this renoprotection is unknown. To investigate this question, we used the 2.5 kb podocin promoter to target Flag-tagged human vitamin D receptor (hVDR) to podocytes in DBA/2J mice. After the induction of diabetes with streptozotocin, transgenic mice had less albuminuria than wild-type controls. In transgenic mice, a low dose of the vitamin D analog doxercalciferol prevented albuminuria, markedly attenuated podocyte loss and apoptosis, and reduced glomerular fibrosis, but it had little effect on the progression of diabetic nephropathy in wild-type mice. Moreover, reconstitution of VDR-null mice with the hVDR transgene in podocytes rescued VDR-null mice from severe diabetes-related renal damage. In culture, 1,25-dihydroxyvitamin D suppressed high-glucose-induced apoptosis of podocytes by blocking p38- and ERK-mediated proapoptotic pathways. Taken together, these data provide strong evidence that vitamin D/VDR signaling in podocytes plays a critical role in the protection of the kidney from diabetic injury.


Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Women: Evidence Report and Systematic Review for the US Preventive Services Task Force.
Postmenopausal status coincides with increased risks for chronic conditions such as heart disease, osteoporosis, cognitive impairment, or some types of cancers. Previously, hormone therapy was used for the primary prevention of these chronic conditions. To update evidence for the US Preventive Services Task Force on the benefits and harms of hormone therapy in reducing risks for chronic conditions. MEDLINE, Cochrane Library, EMBASE, and trial registries from June 1, 2011, through August 1, 2016. Surveillance for new evidence in targeted publications was conducted through July 1, 2017. English-language randomized clinical trials reporting health outcomes. Dual review of abstracts, full-text articles, and study quality; meta-analyses when at least 3 similar studies were available. Beneficial or harmful changes in risks for various chronic conditions. Eighteen trials (n = 40 058; range, 142-16 608; mean age, 53-79 years) were included. Women using estrogen-only therapy compared with placebo had significantly lower risks, per 10 000 person-years, for diabetes (-19 cases [95% CI, -34 to -3]) and fractures (-53 cases [95% CI, -69 to -39]). Risks were statistically significantly increased, per 10 000 person-years, for gallbladder disease (30 more cases [95% CI, 16 to 48]), stroke (11 more cases [95% CI, 2 to 23]), venous thromboembolism (11 more cases [95% CI, 3 to 22]), and urinary incontinence (1261 more cases [95% CI, 880 to 1689]). Women using estrogen plus progestin compared with placebo experienced significantly lower risks, per 10 000 person-years, for colorectal cancer (-6 cases [95% CI, -9 to -1]), diabetes (-14 cases [95% CI, -24 to -3), and fractures (-44 cases [95% CI, -71 to -13). Risks, per 10 000 person-years, were significantly increased for invasive breast cancer (9 more cases [95% CI, 1 to 19]), probable dementia (22 more cases [95% CI, 4 to 53]), gallbladder disease (21 more cases [95% CI, 10 to 34]), stroke (9 more cases [95% CI, 2 to 19]), urinary incontinence (876 more cases [95% CI, 606 to 1168]), and venous thromboembolism (21 more cases [95% CI, 12 to 33]). Hormone therapy for the primary prevention of chronic conditions in menopausal women is associated with some beneficial effects but also with a substantial increase of risks for harms. The available evidence regarding benefits and harms of early initiation of hormone therapy is inconclusive.


High-resolution 7T fMRI of Human Hippocampal Subfields during Associative Learning.
Examining the function of individual human hippocampal subfields remains challenging because of their small sizes and convoluted structures. Previous human fMRI studies at 3 T have successfully detected differences in activation between hippocampal cornu ammonis (CA) field CA1, combined CA2, CA3, and dentate gyrus (DG) region (CA23DG), and the subiculum during associative memory tasks. In this study, we investigated hippocampal subfield activity in healthy participants using an associative memory paradigm during high-resolution fMRI scanning at 7 T. We were able to localize fMRI activity to anterior CA2 and CA3 during learning and to the posterior CA2 field, the CA1, and the posterior subiculum during retrieval of novel associations. These results provide insight into more specific human hippocampal subfield functions underlying learning and memory and a unique opportunity for future investigations of hippocampal subfield function in healthy individuals as well as those suffering from neurodegenerative diseases.


Mild cognitive impairment as a diagnostic entity.
The concept of cognitive impairment intervening between normal ageing and very early dementia has been in the literature for many years. Recently, the construct of mild cognitive impairment (MCI) has been proposed to designate an early, but abnormal, state of cognitive impairment. MCI has generated a great deal of research from both clinical and research perspectives. Numerous epidemiological studies have documented the accelerated rate of progression to dementia and Alzheimer's disease (AD) in MCI subjects and certain predictor variables appear valid. However, there has been controversy regarding the precise definition of the concept and its implementation in various clinical settings. Clinical subtypes of MCI have been proposed to broaden the concept and include prodromal forms of a variety of dementias. It is suggested that the diagnosis of MCI can be made in a fashion similar to the clinical diagnoses of dementia and AD. An algorithm is presented to assist the clinician in identifying subjects and subclassifying them into the various types of MCI. By refining the criteria for MCI, clinical trials can be designed with appropriate inclusion and exclusion restrictions to allow for the investigation of therapeutics tailored for specific targets and populations.


A rapid screening tool for psychological distress in children 3-6years old: results of a validation study.
The mental health needs of young children in humanitarian contexts often remain unaddressed. The lack of a validated, rapid and simple tool for screening combined with few mental health professionals able to accurately diagnose and provide appropriate care mean that young children remain without care. Here, we present the results of the principle cross-cultural validation of the "Psychological Screening for Young Children aged 3 to 6" (PSYCAa3-6). The PSYCa 3-6 is a simple scale for children 3 to 6 years old administered by non-specialists, to screen young children in crises and thereby refer them to care if needed. This study was conducted in Maradi, Niger. The scale was translated into Hausa, using corroboration of independent translations. A cross-cultural validation was implemented using quantitative and qualitative methods. A random sample of 580 mothers or caregivers of children 3 to 6 years old were included. The tool was psychometrically examined and diagnostic properties were assessed comparing the PSYCa 3-6 against a clinical interview as the gold standard. The PSYCa 3-6 Hausa version demonstrated good concurrent validity, as scores correlated with the gold standard and the Clinical Global Impression Severity Scale (CGI-S) [rho = 0.41, p-value = 0.00]. A reduction procedure was used to reduce the scale from 40 to 22 items. The test-retest reliability of the PSYCa 3-6 was found to be high (ICC 0.81, CI95% [0.68; 0.89]). In our sample, although not the purpose of this study, approximately 54 of 580 children required subsequent follow-up with a psychologist. To our knowledge, this is the first validation of a screening scale for children 3 to 6 years old with a cross-cultural validation component, for use in humanitarian contexts. The Hausa version of the PSYCa 3-6 is a reliable and a valuable screening tool for psychological distress. Further studies to replicate our findings and additional validations of the PSYCa 3-6 in other populations may help improve the delivery of mental health care to children.


Comparison of Machine Learning Approaches for Prediction of Advanced Liver Fibrosis in Chronic Hepatitis C Patients.
Using machine learning approaches as non-invasive methods have been used recently as an alternative method in staging chronic liver diseases for avoiding the drawbacks of biopsy. This study aims to evaluate different machine learning techniques in prediction of advanced fibrosis by combining the serum bio-markers and clinical information to develop the classification models. A prospective cohort of 39,567 patients with chronic hepatitis C was divided into two sets-one categorized as mild to moderate fibrosis (F0-F2), and the other categorized as advanced fibrosis (F3-F4) according to METAVIR score. Decision tree, genetic algorithm, particle swarm optimization, and multi-linear regression models for advanced fibrosis risk prediction were developed. Receiver operating characteristic curve analysis was performed to evaluate the performance of the proposed models. Age, platelet count, AST, and albumin were found to be statistically significant to advanced fibrosis. The machine learning algorithms under study were able to predict advanced fibrosis in patients with HCC with AUROC ranging between 0.73 and 0.76 and accuracy between 66.3 and 84.4 percent. Machine-learning approaches could be used as alternative methods in prediction of the risk of advanced liver fibrosis due to chronic hepatitis C.


Use of proton pump inhibitors for the provision of stress ulcer prophylaxis: clinical and economic consequences.
The provision of stress ulcer prophylaxis (SUP) for the prevention of clinically significant bleeding is widely recognized as a crucial component of care in critically ill patients. Nevertheless, SUP is often provided to non-critically ill patients despite a risk for clinically significant bleeding of roughly 0.1 %. The overuse of SUP therefore introduces added risks for adverse drug events and cost, with minimal expected benefit in clinical outcome. Historically, histamine-2-receptor antagonists (H2RAs) have been the preferred agent for SUP; however, recent data have revealed proton pump inhibitors (PPIs) as the most common modality (76 %). There are no high quality randomized controlled trials demonstrating superiority with PPIs compared with H2RAs for the prevention of clinically significant bleeding associated with stress ulcers. In contrast, PPIs have recently been linked to several adverse effects including Clostridium difficile diarrhea and pneumonia. These complications have substantial economic consequences and have a marked impact on the overall cost effectiveness of PPI therapy. Nevertheless, PPI use remains widespread in patients who are at both high and low risk for clinically significant bleeding. This article will describe the utilization of PPIs for SUP and present the clinical and economic consequences linked to their use/overuse.


Sexual orientation and substance abuse treatment utilization in the United States: results from a national survey.
This study examined substance abuse treatment utilization across three dimensions of sexual orientation (identity, attraction, and behavior) in a large national sample of adults in the United States. Prevalence estimates were based on data collected from the 2004-2005 National Epidemiologic Survey on Alcohol and Related Conditions. The sample consisted of 34,653 adults 20 years and older, and represented a population that was 52% women, 71% White, 12% Hispanic, 11% African American, 4% Asian, and 2% other race/ethnicities. An estimated 2% of the target population self-identified as lesbian, gay or bisexual; 4% reported same-sex sexual behavior, and 6% reported same-sex sexual attraction. Sexual minorities, especially women, had a greater likelihood of lifetime substance use disorders and earlier age of drinking onset. The majority of respondents with substance use disorders were untreated and lifetime substance abuse treatment utilization differed based on sexual orientation. Sexual minorities were found to have more extensive family histories of substance abuse problems. The findings indicate the underutilization of substance abuse treatment among all adults, and highlight some important factors to consider when working with sexual minorities.


Ancient human genome sequence of an extinct Palaeo-Eskimo.
We report here the genome sequence of an ancient human. Obtained from approximately 4,000-year-old permafrost-preserved hair, the genome represents a male individual from the first known culture to settle in Greenland. Sequenced to an average depth of 20x, we recover 79% of the diploid genome, an amount close to the practical limit of current sequencing technologies. We identify 353,151 high-confidence single-nucleotide polymorphisms (SNPs), of which 6.8% have not been reported previously. We estimate raw read contamination to be no higher than 0.8%. We use functional SNP assessment to assign possible phenotypic characteristics of the individual that belonged to a culture whose location has yielded only trace human remains. We compare the high-confidence SNPs to those of contemporary populations to find the populations most closely related to the individual. This provides evidence for a migration from Siberia into the New World some 5,500 years ago, independent of that giving rise to the modern Native Americans and Inuit.


Educational disparities in health behaviors among patients with diabetes: the Translating Research Into Action for Diabetes (TRIAD) Study.
Our understanding of social disparities in diabetes-related health behaviors is incomplete. The purpose of this study was to determine if having less education is associated with poorer diabetes-related health behaviors. This observational study was based on a cohort of 8,763 survey respondents drawn from ~180,000 patients with diabetes receiving care from 68 provider groups in ten managed care health plans across the United States. Self-reported survey data included individual educational attainment ("education") and five diabetes self-care behaviors among individuals for whom the behavior would clearly be indicated: foot exams (among those with symptoms of peripheral neuropathy or a history of foot ulcers); self-monitoring of blood glucose (SMBG; among insulin users only); smoking; exercise; and certain diabetes-related health seeking behaviors (use of diabetes health education, website, or support group in last 12 months). Predicted probabilities were modeled at each level of self-reported educational attainment using hierarchical logistic regression models with random effects for clustering within health plans. Patients with less education had significantly lower predicted probabilities of being a non-smoker and engaging in regular exercise and health-seeking behaviors, while SMBG and foot self-examination did not vary by education. Extensive adjustment for patient factors revealed no discernable confounding effect on the estimates or their significance, and most education-behavior relationships were similar across sex, race and other patient characteristics. The relationship between education and smoking varied significantly across age, with a strong inverse relationship in those aged 25-44, modest for those ages 45-64, but non-evident for those over 65. Intensity of disease management by the health plan and provider communication did not alter the examined education-behavior relationships. Other measures of socioeconomic position yielded similar findings. The relationship between educational attainment and health behaviors was modest in strength for most behaviors. Over the life course, the cumulative effect of reduced practice of multiple self-care behaviors among less educated patients may play an important part in shaping the social health gradient.


NADPH oxidase-dependent redox signalling in cardiac hypertrophy, remodelling and failure.
Markers of increased oxidative stress are known to be elevated following acute myocardial infarction and in the context of chronic left ventricular hypertrophy or heart failure, and their levels may correlate with the degree of contractile dysfunction or cardiac deficit. An obvious pathological mechanism that may account for this correlation is the potential deleterious effects of increased oxidative stress through the induction of cellular dysfunction, energetic deficit or cell death. However, reactive oxygen species have several much more subtle effects in the remodelling or failing heart that involve specific redox-regulated modulation of signalling pathways and gene expression. Such redox-sensitive regulation appears to play important roles in the development of several components of the phenotype of the failing heart, for example cardiomyocyte hypertrophy, interstitial fibrosis and chamber remodelling. In this article, we review the evidence supporting the involvement of reactive oxygen species and redox signalling pathways in the development of cardiac hypertrophy and heart failure, with a particular focus on the NADPH oxidase family of superoxide-generating enzymes which appear to be especially important in redox signalling.


Suppression of human colorectal carcinoma cell growth by wild-type p53.
Mutations of the p53 gene occur commonly in colorectal carcinomas and the wild-type p53 allele is often concomitantly deleted. These findings suggest that the wild-type gene may act as a suppressor of colorectal carcinoma cell growth. To test this hypothesis, wild-type or mutant human p53 genes were transfected into human colorectal carcinoma cell lines. Cells transfected with the wild-type gene formed colonies five- to tenfold less efficiently than those transfected with a mutant p53 gene. In those colonies that did form after wild-type gene transfection, the p53 sequences were found to be deleted or rearranged, or both, and no exogenous p53 messenger RNA expression was observed. In contrast, transfection with the wild-type gene had no apparent effect on the growth of epithelial cells derived from a benign colorectal tumor that had only wild-type p53 alleles. Immunocytochemical techniques demonstrated that carcinoma cells expressing the wild-type gene did not progress through the cell cycle, as evidenced by their failure to incorporate thymidine into DNA. These studies show that the wild-type gene can specifically suppress the growth of human colorectal carcinoma cells in vitro and that an in vivo-derived mutation resulting in a single conservative amino acid substitution in the p53 gene product abrogates this suppressive ability.


A combination of eicosapentaenoic acid-free fatty acid, epigallocatechin-3-gallate and proanthocyanidins has a strong effect on mTOR signaling in colorectal cancer cells.
Colorectal cancer (CRC) is one of the major causes of cancer death worldwide. The development of novel anti-CRC agents able to overcome drug resistance and/or off-target toxicity is of pivotal importance. The mammalian target of rapamycin (mTOR) plays a critical role in CRC, regulating protein translation and controlling cell growth, proliferation, metabolism and survival. The aim of this study was to explore the effect of a combination of three natural compounds, eicosapentaenoic acid-free fatty acid (EPA-FFA), epigallocatechin-3-gallate (EGCG) and proanthocyanidins (grape seed [GS] extract) at low cytotoxic concentrations on CRC cells and test their activity on mTOR and translational regulation. The CRC cell lines HCT116 and SW480 were treated for 24h with combinations of EPA-FFA (0-150 µM), EGCG (0-175 µM) and GS extract (0-15 µM) to evaluate the effect on cell viability. The low cytotoxic combination of EPA-FFA 150 µM, EGCG 175 µM and GS extract 15 µM completely inhibited the mTOR signaling in HCT116 and SW480 cells, reaching an effect stronger than or comparable to that of the mTOR inhibitor Rapamycin in HCT116 or SW480 cells, respectively. Moreover, the treatment led to changes of protein translation of ribosomal proteins, c-Myc and cyclin D1. In addition, we found a reduction of clonal capability in both cell lines, with block of cell cycle in G0G1 and induction of apoptosis. Our data suggest that the low cytotoxic combination of EPA-FFA, EGCG and GS extract, tested for the first time here, inhibits mTOR signaling and thus could be considered for CRC treatment.


A systematic review and meta-analysis comparing anterior decompression with fusion and posterior laminoplasty for cervical spondylotic myelopathy.
The optimal surgical procedure for the treatment of cervical spondylotic myelopathy (CSM) remains controversial because there are few comprehensive studies that have investigated the surgical methods. Therefore, we conducted a systematic review and meta-analysis to evaluate evidence in the literature and to compare the surgical outcomes between anterior decompression with fusion (ADF) and laminoplasty, which are representative procedures for CSM. An extensive literature search was performed using PubMed, Embase, and the Cochrane Library to identify comparative studies of ADF and laminoplasty for CSM. The language was restricted to English, and the publication period was from January 2001 to July 2019. We only included studies of CSM and excluded studies that involved patients with ossification of the posterior longitudinal ligament and treatments with posterior instrumented fusion. We extracted outcomes from the studies, such as preoperative and postoperative Japanese Orthopaedic Association (JOA) scores, cervical alignment, surgical complications and reoperation rates. Then, a meta-analysis was performed on these surgical outcomes. Nine studies were obtained, and the quality of the studies was acceptable. In the meta-analysis, the preoperative JOA score was similar between the ADF and laminoplasty groups. The postoperative JOA scores and neurological recovery rates were not different between the ADF and laminoplasty groups. ADF exhibited more favorable results than laminoplasty in terms of postoperative cervical alignment. In contrast, overall complications were more frequently observed in the ADF group than in the laminoplasty group, leading to higher rates of reoperation. However, postoperative neck pain was more frequently observed in the laminoplasty group than in the ADF group. This systematic review and meta-analysis showed both the merits and shortcomings of ADF and laminoplasty. ADF and laminoplasty showed similar results in terms of neurological recovery. Postoperative cervical lordosis was better preserved with ADF than with laminoplasty. However, ADF was associated with a higher incidence of surgical complications than laminoplasty.


Perspective: beyond counting hours: the importance of supervision, professionalism, transitions of care, and workload in residency training.
The medical education community's conversations about residents' duty hours have long focused solely on the number of those hours. In July 2011, the Accreditation Council for Graduate Medical Education (ACGME) enacted its most recent iteration of standards regarding duty hours. Those standards, as well as a 2008 Institute of Medicine report, look beyond the quantity of duty hours to address their quality as well. Indeed, the majority of the 2011 ACGME standards specify requirements for the qualitative components of residents' working and learning environments, including supervision of residents; professionalism, personal responsibility, and patient safety; transitions of care; and clinical responsibilities (including workload). The authors believe that focusing on these qualitative (rather than quantitative) components of the resident's working and learning environment provides the greatest promise for balancing patient care with resident education, thus optimizing the safety and effectiveness of both. For each of the four qualitative components that the authors discuss (enhancing supervision, nurturing professionalism and personal responsibility, ensuring safe transitions of care, and optimizing workloads and cognitive loads), they offer agendas for faculty development, educational program planning, and research. Thus, the authors call on the medical education community to expand its discussion beyond counting duty hours to focus on these critical issues that ensure quality resident education and patient care and to implement necessary strategies to address them.


Berry anthocyanin intake and cardiovascular health.
Over half of all cardiovascular (CV) events could be prevented by improved diet. This is reflected in government targets for fruit/vegetable intake, yet these are variable across the world (UK: 5-a-day; USA: 9-a-day), do not identify specific fruits/vegetables, and prove hard to achieve. Mounting evidence from prospective studies, supported by recent randomised controlled trials suggest that the benefits of fruits/vegetables may be due to bioactive substances called flavonoids. Specifically one sub-class of flavonoids, the anthocyanins, responsible for the red/blue hue, are receiving growing attention. Although promising data is emerging from cohort studies, and cell/animal studies, proof of efficacy from longer-term randomised controlled trials, and an understanding of the importance of differential metabolism in relation to clinical efficacy are distinctly lacking. Diet related ill-health are among the leading priorities of our time and simple dietary change, including incorporating a few portions of anthocyanin-rich fruit into our diet could have a significant impact at a public health level.


Analysis of Land Use Change and Urbanization in the Kucukcekmece Water Basin (Istanbul, Turkey) with Temporal Satellite Data using Remote Sensing and GIS.
Accurate and timely information about land use and land cover (LULC) and its changes in urban areas are crucial for urban land management decision-making, ecosystem monitoring and urban planning. Also, monitoring and representation of urban sprawl and its effects on the LULC patterns and hydrological processes of an urbanized watershed is an essential part of water resource planning and management. This paper presents an image analysis study using multi temporal digital satellite imagery of LULC and changes in the Kucukcekmece Watershed (Metropolitan Istanbul, Turkey) from 1992 to 2006. The Kucukcekmece Basin includes portions of the Kucukcekmece District within the municipality of Istanbul so it faces a dramatic urbanization. An urban monitoring analysis approach was first used to implement a land cover classification. A change detection method controlled with ground truth information was then used to determine changes in land cover. During the study period, the variability and magnitude of hydrological components based on land-use patterns were cumulatively influenced by urban sprawl in the watershed. The proposed approach, which uses a combination of Remote Sensing (RS) and Geographical Information System (GIS) techniques, is an effective tool that enhances land-use monitoring, planning, and management of urbanized watersheds.


[National program of early detection of cancer in Croatia].
A well organized and conducted program of cancer screening at the population level should be scientifically based, cost-effective at long term, and designed on the good practice examples. Appropriate diagnosis and treatment should be warranted by high rate of target population inclusion, while appropriate diagnosis and treatment should be warranted for those with positive findings. The aim is to present implementation of the national programs of early detection of breast and colon cancer in Croatia. In the first cycle screening for breast cancer (since the end of 2006), a total of 720,981 women were invited for mammography, of which 58.5% presented for screening, with more than 1500 cases of breast cancer detected. A total of 808,913 tests were distributed for colon cancer screening from the end of 2007 to the beginning of 2010, of which only 19.9% were returned, 7.7% of these positive. Colonoscopy yielded 77.5% of pathologic findings, including 388 (5.99%) carcinomas, 2492 (38.46%) polyps, 1641 hemorrhoids and 998 diverticula. In Croatia, the public health service has made maximal use of all its resources in the national programs of early cancer detection. Great efforts and time, along with continuous education of all those involved in the program, have been invested in preparatory activities, organization and coordination of the program, contacts and collaboration with family physicians, specialist units, mass media, regional and local authorities, partnership with non-governmental societies, monitoring, evaluation and quality control.


Exploring UK doctors' attitudes towards online patient feedback: Thematic analysis of survey data.
Patients are increasingly using online platforms to give feedback about their health-care experiences. Online feedback has been proposed as a way to drive transformative change in the health service through informing choice and improving quality. Attitudes held by health-care professionals influence the uptake of new technologies. Understanding these attitudes is essential in exploring the potential of online patient feedback as a standard feedback mechanism. This study explores the content of free-text comments left by doctors responding to a survey with the aim of understanding their attitudes towards online feedback. A cross-sectional online questionnaire was completed by 1001 UK primary and secondary-care doctors. Doctors were given the opportunity to leave a free-text comment about online patient feedback. Doctors' attitudes towards online patient feedback were identified and explored using thematic analysis. Descriptive statistics and chi-square tests were used to examine demographic differences between those doctors who left a comment and those who did not. Thematic analysis identified five key interrelated themes: anonymity, confidentiality, representativeness, moderation/regulation of online feedback and platform type. The characteristics of those leaving a comment very closely matched those of the entire survey sample. Across the comments, the most prominent finding was a general scepticism and caution towards online feedback, with most of the key themes relating to the perceived limitations and challenges. Further work exploring ways of addressing and verifying online comments without breaching confidentiality could provide valuable information to health systems seeking to drive improvement through patient online feedback.


Analyses of the local control of pulmonary Oligometastases after stereotactic body radiotherapy and the impact of local control on survival.
Successful local therapy for oligometastases may lead to longer survival. The purpose of this multicentre retrospective study was to investigate factors affecting the local control (LC) of pulmonary oligometastases treated by stereotactic body radiotherapy (SBRT) and to investigate the impact of LC on survival. The inclusion criteria included 1 to 5 metastases, the primary lesion and other extrathoracic metastases were controlled before SBRT, and the biological effective dose (BED10) of the SBRT was 75 Gy or more. The Cox proportional hazards model was used for analyses. Data of 1378 patients with 1547 tumours from 68 institutions were analysed. The median follow-up period was 24.2 months. The one-year, 3-year and 5-year LC rates were 92.1, 81.3 and 78.6%, respectively, and the 1-year, 3-year and 5-year overall survival rates were 90.1, 60.3 and 45.5%, respectively. Multivariate analysis for LC showed that increased maximum tumour diameter (p = 0.011), type A dose calculation algorithm (p = 0.005), shorter overall treatment time of SBRT (p = 0.035) and colorectal primary origin (p < 0.001 excluding oesophagus origin) were significantly associated with a lower LC rate. In the survival analysis, local failure (p < 0.001), worse performance status (1 vs. 0, p = 0.013; 2-3 vs. 0, p < 0.001), oesophageal primary origin (vs. colorectal origin, p = 0.038), squamous cell carcinoma (vs. adenocarcinoma, p = 0.006) and increased maximum tumour diameter (p < 0.001) showed significant relationships with shorter survival. Several factors of oligometastases and SBRT affected LC. LC of pulmonary oligometastases by SBRT showed a significant survival benefit compared to patients with local failure.