Recommendations for determining the validity of consumer wearable heart rate devices: expert statement and checklist of the INTERLIVE Network.
Assessing vital signs such as heart rate (HR) by wearable devices in a lifestyle-related environment provides widespread opportunities for public health related research and applications. Commonly, consumer wearable devices assessing HR are based on photoplethysmography (PPG), where HR is determined by absorption and reflection of emitted light by the blood. However, methodological differences and shortcomings in the validation process hamper the comparability of the validity of various wearable devices assessing HR. Towards Intelligent Health and Well-Being: Network of Physical Activity Assessment (INTERLIVE) is a joint European initiative of six universities and one industrial partner. The consortium was founded in 2019 and strives towards developing best-practice recommendations for evaluating the validity of consumer wearables and smartphones. This expert statement presents a best-practice validation protocol for consumer wearables assessing HR by PPG. The recommendations were developed through the following multi-stage process: (1) a systematic literature review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, (2) an unstructured review of the wider literature pertaining to factors that may introduce bias during the validation of these devices and (3) evidence-informed expert opinions of the INTERLIVE Network. A total of 44 articles were deemed eligible and retrieved through our systematic literature review. Based on these studies, a wider literature review and our evidence-informed expert opinions, we propose a validation framework with standardised recommendations using six domains: considerations for the target population, criterion measure, index measure, testing conditions, data processing and the statistical analysis. As such, this paper presents recommendations to standardise the validity testing and reporting of PPG-based HR wearables used by consumers. Moreover, checklists are provided to guide the validation protocol development and reporting. This will ensure that manufacturers, consumers, healthcare providers and researchers use wearables safely and to its full potential.


Ethnic differences in term birthweight: the role of constitutional and environmental factors.
It is not clear to what extent ethnic differences in the term birthweight distribution are constitutional or pathological. This study explored term birthweight heterogeneity between ethnic groups and the explanatory role of constitutional and environmental factors. As part of a prospective cohort study, the Amsterdam Born Children and their Development study, 8266 pregnant women filled out a questionnaire during early pregnancy. Ethnic groups were categorised as: native Dutch group; first and second generation Surinamese, Antillean, Turkish, Moroccan, Ghanaian and other non-Dutch groups. Only singleton livebirths with >or=37.0 weeks of gestation and with complete data were included for analysis (n = 7118). We performed linear regression analyses to estimate the association between ethnicity and, for gestational age, standardised birthweight at term, adjusted for constitutional (fetal gender, parity, maternal age, maternal height) and environmental (education, cohabitation status, maternal body mass index, smoking, alcohol consumption, depression, work stress) determinants respectively. Mean birthweight ranged from 3223 g (second generation Surinamese newborns) to 3548 g (Dutch newborns). Adjustment for constitutional factors substantially reduced the ethnic differences in birthweight, while adjustment for environmental factors provided little additional explanation. Surinamese [first generation: regression coefficient (b) = -98.3 g, P < 0.001; second generation: b = -159.3 g, P < 0.001], first generation Antillean (b = -102.0 g, P = 0.037), and Ghanaian newborns (b = -120.7 g, P = 0.001) remained significantly smaller than Dutch newborns after adjustment for all determinants. Term birthweight differences between Dutch newborns and Turkish, Moroccan and other non-Dutch newborns were largely explained by constitutional rather than environmental determinants, limiting the need for prevention. Surinamese, Antillean and Ghanaian (mainly black) newborns remained unexplainably smaller after adjustment, leaving the possibility of either unknown constitutional or pathological underlying mechanisms.


Deep & Wide. Health care boards look beyond their communities for new trustees.
Trend watchers stop short of calling it a groundswell, but broader board membership is gaining support. "Traditionally, governance on behalf of a community has meant governance by the community," says one consultant. "Changing circumstances are challenging that convention." Driving the trend are changes often initiated by trustees themselves.


N.m.r. and e.p.r. investigation of the interaction of copper(II) and glycyl-L-histidyl-L-lysine, a growth-modulating tripeptide from plasma.
Interaction of Cu(II) and Gly-His-Lys, a growth-modulating tripeptide from plasma, was investigated by 13C- and 1H-n.m.r. and e.p.r. spectroscopy. The n.m.r. line-broadening was interpreted in terms of major and minor species formed as a function of pH. The results indicate that the n.m.r. line-broadening is due to the presence of minor species in rapid exchange and not due to the major species in solution, which has a large tau M. It is concluded that the technique of 13C- and 1H-n.m.r. line broadening, caused by paramagnetic Cu(II) ion, should be undertaken with caution, since the method may not be useful for obtaining structural information on the major species. The e.p.r. spectra over a wide pH range are almost entirely due to similarly co-ordinating species. Starting at pH 5.5, the narrowest absorption near 340 mT shows superhyperfine structure, which comes out sharply in the pH region 6.0-9.6. The spectra in this pH range showed the seven lines of nitrogen superhyperfine splitting, indicating clearly the co-ordination of three nitrogen atoms to Cu(II). The e.p.r. parameters in the medium pH range, A parallel = 19.5 mT and g parallel = 2.21, fit well with the contention that Cu(II) is ligated to Gly-His-Lys through one oxygen atom and three nitrogen atoms in a square-planar configuration.


[The development and use of an immunoenzyme test system for detecting and the species identification of the monkey pox virus].
An enzyme immunoassay (EIA) system for the species-specific diagnosis of monkeypox, based on the use of monoclonal antibodies (McAb) to monkeypox virus, has been developed. Immunoglobulins, isolated from McAb-containing cultural and immune ascitic fluids, have been conjugated with horse-radish peroxidase and used as detector antibodies. For immunosorption, rabbit polyclonal antibodies to the vaccine virus have been used. The specificity and sensitivity of the EIA system thus obtained have been tested on animals and humans having monkeypox and confirmed by traditional diagnostic methods (the isolation of the virus on chick embryo chorioallantoic membranes and in cell culture).


Strategic, value-based delivery in global health care: innovations at Harvard University and Brigham and Women's Hospital.
Investments in global health have more than doubled over the past decade, generating a cadre of new institutions. To date, most of the funded research in global health has focused on discovery, and, more recently, on the development of new tools, which has tightened the implementation bottleneck. This article introduces the concept of global health delivery and the need to catalog and analyze current implementation efforts to bridge gaps in delivery. Global health delivery is complex and context-dependent and requires an interdisciplinary effort, including the application of strategic principles. Furthermore, delivery is necessary to ensure that the investments in research, discovery, and development generate value for patients and populations. This article discusses the application of value-based delivery to global health. It provides some examples of approaches to aggregating implicit knowledge to inform practice. With global health delivery, the aim is to transform global health scale-up from a series of well-intentioned but often disconnected efforts to a value-based movement based upon 21st-century technology, standards, and efficiency.


The greening after extended darkness1 is an N-end rule pathway mutant with high tolerance to submergence and starvation.
Plants respond to reductions in internal oxygen concentrations with adaptive mechanisms (for example, modifications of metabolism to cope with reduced supply of ATP). These responses are, at the transcriptional level, mediated by the group VII Ethylene Response Factor transcription factors, which have stability that is regulated by the N-end rule pathway of protein degradation. N-end rule pathway mutants are characterized by a constitutive expression of hypoxia response genes and abscisic acid hypersensitivity. Here, we identify a novel proteolysis6 (prt6) mutant allele, named greening after extended darkness1 (ged1), which was previously discovered in a screen for genomes uncoupled-like mutants and shows the ability to withstand long periods of darkness at the seedling stage. Interestingly, this ethyl methanesulfonate-derived mutant shows unusual chromosomal rearrangement instead of a point mutation. Furthermore, the sensitivity of N-end rule pathway mutants ged1 and prt6-1 to submergence was studied in more detail to understand previously contradicting experiments on this topic. Finally, it was shown that mutants for the N-end rule pathway are generally more tolerant to starvation conditions, such as prolonged darkness or submergence, which was partially associated with carbohydrate conservation.


Heritable differences in schooling behavior among threespine stickleback populations revealed by a novel assay.
Identifying the proximate and ultimate mechanisms of social behavior remains a major goal of behavioral biology. In particular, the complex social interactions mediating schooling behavior have long fascinated biologists, leading to theoretical and empirical investigations that have focused on schooling as a group-level phenomenon. However, methods to examine the behavior of individual fish within a school are needed in order to investigate the mechanisms that underlie both the performance and the evolution of schooling behavior. We have developed a technique to quantify the schooling behavior of an individual in standardized but easily manipulated social circumstances. Using our model school assay, we show that threespine sticklebacks (Gasterosteus aculeatus) from alternative habitats differ in behavior when tested in identical social circumstances. Not only do marine sticklebacks show increased association with the model school relative to freshwater benthic sticklebacks, they also display a greater degree of parallel swimming with the models. Taken together, these data indicate that marine sticklebacks exhibit a stronger tendency to school than benthic sticklebacks. We demonstrate that these population-level differences in schooling tendency are heritable and are shared by individuals within a population even when they have experienced mixed-population housing conditions. Finally, we begin to explore the stimuli that elicit schooling behavior in these populations. Our data suggest that the difference in schooling tendency between marine and benthic sticklebacks is accompanied by differential preferences for social vs. non-social and moving vs. stationary shelter options. Our study thus provides novel insights into the evolution of schooling behavior, as well as a new experimental approach to investigate the genetic and neural mechanisms that underlie this complex social behavior.


The nested assembly of plant-animal mutualistic networks.
Most studies of plant-animal mutualisms involve a small number of species. There is almost no information on the structural organization of species-rich mutualistic networks despite its potential importance for the maintenance of diversity. Here we analyze 52 mutualistic networks and show that they are highly nested; that is, the more specialist species interact only with proper subsets of those species interacting with the more generalists. This assembly pattern generates highly asymmetrical interactions and organizes the community cohesively around a central core of interactions. Thus, mutualistic networks are neither randomly assembled nor organized in compartments arising from tight, parallel specialization. Furthermore, nestedness increases with the complexity (number of interactions) of the network: for a given number of species, communities with more interactions are significantly more nested. Our results indicate a nonrandom pattern of community organization that may be relevant for our understanding of the organization and persistence of biodiversity.


[Cardiovascular risk and cardiometabolic risk: an epidemiological evaluation].
On the basis of a critical literature review, this article deals with the concepts of global cardiovascular risk and cardiometabolic risk, pointing out their links but also their unresolved issues and discussing their usefulness in clinical practice. The global cardiovascular risk is the probability of suffering from a coronary event or stroke in a given period of time and in this sense it is an absolute risk, generally reported as percentage at 10 years. Usually risk functions are used, derived from longitudinal studies of healthy people at baseline. They consider some factors that are coherently linked with events in population analyses: among these there are some metabolic factors (total cholesterol, HDL cholesterol, fasting blood glucose), some biological factors (blood pressure) and some lifestyle factors (tobacco smoking), all modifiable beyond those non-modifiable like age and gender. The chosen factors must be independent at multivariate analysis, simple and standardized to measure, and contribute to significantly increase the risk-function predictivity. To be reliable, these risk functions must be derived from the same population where they will be later administered. For this reason the Italian Progetto CUORE, in the longitudinal study section, built a database of risk factors from longitudinal comparable studies started between the mid '80s and '90s and followed up the participants for cardiovascular mortality and morbidity to estimate the Italian global cardiovascular risk (first coronary or cerebrovascular event) for men and women. Two tools have been produced, the risk charts and a score software (see www.cuore.iss.it). The ongoing epidemics of obesity and diabetes and the fact that diabetes is associated with classical risk factors like hypertension and dyslipidemia induced the American Diabetes Association and the American Heart Association to launch a "call to action" to prevent both cardiovascular disease and diabetes. In this paper, as cardiometabolic risk factors were considered those "closely related to diabetes and cardiovascular disease: fasting/postprandial hyperglycemia, overweight/obesity, elevated systolic and diastolic blood pressure, and dyslipidemia". The association among the cardiometabolic risk factors has been known for a long time, and much of their etiology has been ascribed to insulin resistance. Also, the fact that these "metabolic" abnormalities can cluster in many individuals gave rise to the term "metabolic syndrome", a construct embraced by many organizations but questioned by other authors. From an epidemiological point of view the metabolic syndrome seems to increase modestly the cardiovascular risk, whereas in non-diabetic individuals it predicts diabetes much more efficiently. Many studies have compared the performance of the classical cardiovascular evaluation tools (the Framingham risk score, the SCORE charts, the Progetto CUORE score) and metabolic syndrome in cardiovascular disease prediction. Usually in people at high risk the presence of the metabolic syndrome does not improve the risk, whereas in people at lower risk its presence increases significantly the chances of cardiovascular disease. Many studies have shown that positive lifestyle interventions markedly reduce the rate of progression of type 2 diabetes. Also some drugs were tested for diabetes prevention, usually in people with impaired glucose tolerance. Oral diabetes drugs considered together (acarbose, metformin, flumamine, glipizide, phenformin) were less effective than lifestyle interventions, with different results among the drugs; the antiobesity drug orlistat gave similar results to lifestyle interventions. In Italy an appropriate approach to cardiovascular disease and diabetes prevention may be that of first evaluating the global cardiovascular risk using the charts or the score software of the Progetto CUORE, because high-risk subjects (> or =20%) must be treated aggressively independently of the presence of the metabolic syndrome; as a second step the metabolic syndrome may be sought, because it increases the risk; finally some attention should be paid to non-diabetic hyperglycemic individuals.


Identification of the first glyphosate-resistant capeweed (Arctotheca calendula) population.
Glyphosate is routinely used in Australia to control the Arctotheca species Arctotheca calendula (L.) Levyns (referred hereinafter as capeweed). This study identifies the first global case of field-evolved glyphosate-resistant capeweed, collected from the grainbelt of Western Australia. In 2020, a capeweed biotype that was collected from Borden in the southern Western Australian grainbelt was confirmed to be glyphosate-resistant (referred hereinafter as Spence population). When compared to the pooled mortality of six field-collected, glyphosate susceptible capeweed populations (S1, S2, S3, S4, S5 and S6), the Spence population was found > 11-fold more resistant to glyphosate than the pooled results of the susceptible populations (S1-S6) at the lethal dose of 50% (LD50 ) level. The growth of the Spence population was also less affected, requiring > 13-fold more glyphosate to reduce growth than the pooled susceptible populations at the growth reduction of 50% (GR50 ) level. Sequencing of the plastidic 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene indicated no known single gene mutation imparting glyphosate resistance. This study, however, did not investigate any other known mechanisms that impart glyphosate resistance. When screened at the field-applied rate, this Spence population was also found to survive an inhibitor of acetolactate synthase (ALS) (metosulam) and an inhibitor of phytoene desaturase (diflufenican). This is the first confirmation of glyphosate resistance evolution in a capeweed population globally. With capeweed resistance already confirmed to photosystem-I inhibiting herbicides (paraquat and diquat), this study emphasizes the importance of using integrated measures that do not depend only on the use of non-selective herbicides for controlling herbicide resistance-prone capeweed populations. © 2021 Society of Chemical Industry.


Unsymmetrical Trifluoromethyl Methoxyphenyl β-Diketones: Effect of the Position of Methoxy Group and Coordination at Cu(II) on Biological Activity.
Copper(II) complexes with 1,1,1-trifluoro-4-(4-methoxyphenyl)butan-2,4-dione (HL1) were synthesized and characterized by elemental analysis, FT-IR spectroscopy, and single crystal X-ray diffraction. The biological properties of HL1 and cis-[Cu(L1)2(DMSO)] (3) were examined against Gram-positive and Gram-negative bacteria and opportunistic unicellular fungi. The cytotoxicity was estimated towards the HeLa and Vero cell lines. Complex 3 demonstrated antibacterial activity towards S. aureus comparable to that of streptomycin, lower antifungal activity than the ligand HL1 and moderate cytotoxicity. The bioactivity was compared with the activity of compounds of similar structures. The effect of changing the position of the methoxy group at the aromatic ring in the ligand moiety of the complexes on their antimicrobial and cytotoxic activity was explored. We propose that complex 3 has lower bioavailability and reduced bioactivity than expected due to strong intermolecular contacts. In addition, molecular docking studies provided theoretical information on the interactions of tested compounds with ribonucleotide reductase subunit R2, as well as the chaperones Hsp70 and Hsp90, which are important biomolecular targets for antitumor and antimicrobial drug search and design. The obtained results revealed that the complexes displayed enhanced affinity over organic ligands. Taken together, the copper(II) complexes with the trifluoromethyl methoxyphenyl-substituted β-diketones could be considered as promising anticancer agents with antibacterial properties.


Feeling unreal: a functional imaging study in patients with Kleine-Levin syndrome.
Kleine-Levin syndrome is characterized by relapsing-remitting episodes of severe hypersomnia, cognitive impairment, apathy, derealization and behavioural disturbances. Between episodes, patients have normal sleep, mood and behaviour. Functional imaging studies performed in small series of patients with Kleine-Levin syndrome with visual or semi-quantitative, uncontrolled analysis yielded equivocal brain changes. Using whole brain voxel-based group analysis, we compared brain perfusion scintigraphy during and between episodes in consecutive patients with Kleine-Levin syndrome versus healthy control subjects and correlated perfusion changes with disease severity and symptoms, focusing on less studied but disabling symptoms, such as apathy and derealization. During asymptomatic periods, 41 patients (mean age of 22.3 ± 8.1 years, 56.1% male) and 15 age- and sex-matched healthy control subjects underwent single-photon emission computed tomography scanning with technetium-99m ethyl cysteinate dimer. Eleven patients repeated the test during a symptomatic period. Compared with controls, patients during asymptomatic periods had persistent hypoperfusion in the hypothalamus, the thalamus (mainly the right posterior part), the caudate nucleus, and cortical associative areas, including the anterior cingulate, (Brodmann area 25), the orbito-frontal (Brodmann area 11) and the right superior temporal cortices (Brodmann area 22), extending to the insula (P < 0.001 in all area). Two additional hypoperfused areas emerged during symptomatic periods (P < 0.001), located in the right dorsomedial prefrontal cortex (Brodmann area 8) and the right parieto-temporal junction (Brodmann areas 22 and 39). These two areas were more affected between episodes, when the mean episode duration was longer (r = -0.53; P < 0.001). The score for the Depersonalization/Derealization Inventory during symptomatic periods strongly correlated with the hypoperfusion of the right (r = -0.74, P < 0.001) and left (r = -0.59, P < 0.005) parieto-temporal junctions. No hyperperfusion was found. Because the parieto-temporal junction (including the angular gyrus) is involved in cross-modal association between somatosensory (body knowledge), auditory and visual information, the robust hypoperfusions and correlations observed in this area may underlie the striking derealization reported by patients during episodes. Defects in the dorsomedial prefrontal cortex may cause apathy. Persistent hypoperfusion in the diencephalic and associative cortical area during asymptomatic periods is a marker of the disease, suggestive of a scenario wherein patients compensate for these deficient circuitries.


Severe polyneuropathy in a patient with Churg-Strauss syndrome.
We describe the clinicopathologic features of a 56-year-old woman affected with Churg-Strauss syndrome with major peripheral nerve involvement. The patient presented with a 1-month history of mainly distal upper-limb symmetrical paresthesias and hypostenia (bilateral "wrist drop"), palpable purpura and eosinophilia. Multiple pulmonary infiltrates and asthma had been present since the age of 52. Skin biopsy demonstrated an eosinophilic necrotizing vasculitis. During the hospitalization she was submitted to cardiac, bronchopulmonary, renal, and gastrointestinal evaluation and EMG. Peripheral nerve and skeletal muscle biopsies were performed. Sural nerve biopsy showed a marked degree of demyelination. A perivascular cellular infiltrate within the epineurium was immunoreactive for T lymphocytes and macrophages. Strong HLA-DR immunostaining was present in the endoneurium. IgM, IgE and fibrinogen deposition was found in some epi- and endoneurial vessels. Muscle biopsy showed neurogenic changes and 1 thrombosed vessel surrounded by mononuclear cells. Membrane attack complex (MAC) deposition was present in a few capillaries and major histocompatibility complex products I (MHCP I) was expressed at the subsarcolemmal level in a few isolated perivascular muscle fibers. After immunosuppressive therapy, the patient showed progressive improvement of both clinical symptoms and neurophysiological parameters.


Adapting a Cancer Screening Education Program for Native American Women with Disabilities.
Like other minoritized groups, people with disabilities experience lack of access to health care. People with intellectual and developmental disabilities (IDD), which are lifelong disabilities diagnosed in childhood requiring varying levels of support for completing daily activities, are less likely to receive preventive health care such as cancer screening. Furthermore, Native American women are less likely than White women to receive cancer screenings. In this qualitative research with Native American women with IDD, their caregivers, healthcare and service providers, and community leaders, we asked, "What are the influences on breast and cervical cancer screening for Native American women with IDD?" with the goal of adapting an existing cancer screening education program. Semi-structured in-depth interviews (N = 48) were audio recorded and transcribed verbatim for analysis. Two coders used a constant comparative method to code and revise the a priori codebook with subthemes and new codes. Results highlighted individual, interpersonal, and community/institutional influences on screening, emphasizing the individual effects of social inequity on this population, the importance of ableist bias in recommending cancer screenings, and opportunities to integrate traditional ways of knowing with allopathic medicine. Results of this work were used to adapt a cancer screening education program for Native American women with IDD.


The role of ATP in the control of H+-galactoside symport in the yeast Kluyveromyces marxianus.
Transport of methyl beta-D-thiogalactoside and p-nitrophenyl beta-D-galactoside is shown to proceed through the H+-lactose symporter of Kluyveromyces marxianus. Uptake of these compounds is strongly reduced under anaerobic conditions or aerobically in the presence of antimycin. It is shown that antimycin treatment affects p-nitrophenyl beta-D-galactoside uptake in a similar way as it affects the cellular amount of ATP, suggesting regulation of p-nitrophenyl beta-D-galactoside transport by ATP. Also, manipulation of cellular ATP by antimycin treatment followed by glucose incubation, or by aerobic incubation of cells with 2-deoxy-D-glucose, showed a similar dependence of galactoside uptake on the ATP level. Transport of the lipophilic cation tetraphenylphosphonium is affected by ATP variations in a similar way as galactoside influx. It is concluded that ATP regulates H+-galactoside symport by its influence on charge translocation. It is discussed that a membrane ATPase probably plays a central role in the control of the activity of H+-sugar symport.


Comparison of powder produced by evaporative precipitation into aqueous solution (EPAS) and spray freezing into liquid (SFL) technologies using novel Z-contrast STEM and complimentary techniques.
The objective of this study was to compare the properties of particles formed by nucleation and polymer stabilization (e.g. evaporative precipitation into aqueous solution (EPAS)) versus rapid freezing (e.g. spray freezing into liquid (SFL)). Powders formed by EPAS and SFL, composed of danazol and PVP K-15 in a 1:1 ratio, were characterized using X-ray powder diffraction, modulated differential scanning calorimetry (MDSC), contact angle determination, dissolution, scanning electron microscopy (SEM), environmental scanning electron microscopy (ESEM), BET specific surface area, and Z-contrast scanning transmission electron microscopy (STEM). Large differences in particle morphologies and properties were observed and explained in terms of the particle formation mechanisms. Both techniques produced amorphous powders with high T(g) and low contact angle values. However, STEM analysis showed highly porous bicontinuous nanostructured 30nm particles connected by narrow bridges for SFL versus aggregated 500 nm primary particles for EPAS. The combination of STEM and other characterization techniques indicates solid solutions were formed for the SFL powders consistent with rapid freezing. In contrast, the EPAS particle cores are enriched in hydrophobic API and the outer surface is enriched in the hydrophilic polymer, with less miscibility than in the SFL powders. Consequently, dissolution rates are faster for the SFL particles, although both techniques enhanced dissolution rates of the API.


[Extrahepatic cholestasia during therapy with Zolmitriptan (AscoTop)].
Because of recurrent abdominal pain, jaundice and elevated liver function tests, a sixty-two-year old man had been referred to hospital several times within the preceding six months. By means of ultrasonography, endoscopic retrograde cholangiopancreatography (ERCP) and magnetic resonant cholangiopancreatography, dilated extrahepatic bile ducts were diagnosed. Stones and a tumorous process were excluded. ERCP showed hypermotility of the upper gastrointestinal tract. Quantitative hepatobiliary scintigraphy demonstrated retention of activity in the intra- and extrahepatic bile ducts and delayed transit of activity to the duodenum as signs of papillary dysfunction. Drug anamnesis revealed that the patient had started migraine treatment with Zolmitiptan, a 5-HT (1B/1D)-receptor agonist of the second generation, six months before the beginning of the cholestasia syndrome. Because of the known increase in amplitudes of oesophageal motor waves and of lower oesophageal sphincter tone by Sumatriptan, a 5-HT (1B/1D)-receptor agonist of the first generation, Zolmitriptan treatment was stopped. Thereupon, laboratory findings normalised and the patient has been feeling well for more than one year. Serotonin is an important monamine neurotransmitter that acts both in the CNS and in the gastrointestinal tract on identical receptors and is transported by the same systems. Thus it is not surprising that therapeutic measures which influence the serotoninergic system in the CNS are also effective in the enteric nervous.


Cognitive dysfunction in systemic lupus erythematosus is associated with disease activity and oxidative stress: a comparative study with rheumatoid arthritis for identifying biomarkers.
The prevalence and pathophysiological mechanisms of cognitive deficits (CD) Systemic Lupus Erythematosus (SLE) and Rheumatoid arthritis (RA) are very heterogeneous and poorly understood. We characterized CD in patients with SLE compared with RA patients and healthy controls. We compared the neuropsychological profile of SLE and RA with patients' oxidative/inflammatory biomarkers for CD. We performed a cross-sectional study, including 50 SLE patients, 29 RA patients, and 32 healthy controls. SLEDAI and DAS28 assessed disease activity. SF-36 questionnaire and a battery of cognitive tests were applied to all participants. Blood samples were collected to determine IL-6, S100ß, myeloperoxidase (MPO), malondialdehyde and reduced glutathione (GSH) alterations. In the SLE group, higher GSH was associated with the absence of CD (With CD = 69 ± 49, Without CD = 112 ± 81, p = 0.030), while higher IL-6 was associated with the presence of CD in the RA group (With CD = 603 ± 173, Without CD = 431 ± 162, p = 0.032). Regarding specific cognitive domains, in SLE higher MPO was associated with poor performance in reasoning and abstraction (p = 0.039), higher IL-6 was associated with poor performance in inhibitory control and attention (p = 0.031), and higher GSH was associated with better performance in memory(p = 0.021). Higher SLEDAI was associated with poor performance in semantic fluency(p = 0.031), inhibitory control, and attention in the SLE group(p = 0.037). In the RA group, higher DAS-28 was associated with poor performance in executive functions(p = 0.016) and phonemic fluency (p = 0.003). SLE patients' disease activity, inflammatory state, and oxidative stress were associated with CD. In RA patients, CD was associated with disease activity and inflammatory state. These results encourage further studies with larger samples aiming to confirm oxidative stress parameters as biomarkers of CD in SLE patients.


Epidemiological study of burn patients hospitalised at a burns centre, Manipal.
Burn injuries constitute a major public health problem and account for a significant cause of mortality and morbidity amongst the Indian population. This 2-year prospective study was undertaken to find out the exact epidemiological determinants of 737 patients admitted with burn injuries and, thus, to try and formulate effective preventive strategies. This study was conducted in the department of plastic surgery and burns from September 2011 to June 2013. All consecutive patients with major burns admitted for in-hospital treatment during the study period were included in the study. The data collected included age, gender, cause and mode of burns, total burn surface area (TBSA), microbiological profile and outcome. More than 55% of the patients were female (58.61%). The mean age was 31.3 years ranging from 8 months to 89 years. A higher number of females (97.5%) sustained burn injuries at home compared with 36.11% males sustaining injuries outdoors. (P = 0.000). Almost one third of injuries (40.36%) occurred between 4 pm and 8 pm, followed by 28% between 7 am and 12 noon. Synthetic garments were worn by 70% of females at the time of injury, whereas 40% of males had worn mixed clothing (P = 0.000). Flame injuries contributed to 80.1% of burns in females (P = 0.006). The rate of electrical injuries (9.8%) was significantly higher in males (P = 0.005). In almost 40% of males, TBSA was <19%, whereas in 40% of females, TBSA was >68%. (P = 0.004). Microbial profile showed that pseudomonas aeruginosa (n = 260; 35.3%), Klebsiella pneumoniae (n = 209; 28.5%), and Escherichia coli (n = 145; 22.6%) were the most frequent types of Staphylococci bacterial growths. The cause for burn injury was ignition of clothes in 68.74% females, and in 35.48% males, it was because of an attempt to save other burn injury victims (P = 0.013) The case fatality rate was 29.3%. A majority of the males (60.7%) recovered, whereas 45.89% of females succumbed because of their burn injury. (P = 0.001). As the aetiological factors of burn injuries vary considerably in different communities, careful study of the pattern in every community is needed before a sound prevention programme can be planned and implemented. Hence, this study was conducted to assess epidemiological, modes, causes, and risk factors and the microbial profile of burn injuries and to study the outcomes.


A pollinator shift explains floral divergence in an orchid species complex in South Africa.
Floral diversification driven by shifts between pollinators has been one of the key explanations for the radiation of angiosperms. According to the Grant-Stebbins model of pollinator-driven speciation, these shifts result in morphologically distinct 'ecotypes' which may eventually become recognizable as species. The current circumscription of the food-deceptive southern African orchid Eulophia parviflora encompasses a highly variable monophyletic species complex. In this study, two forms were identified within this complex that differ in distribution, floral morphology, scent chemistry and phenology, and a test was made of whether these differences represent adaptations for different pollinators. Multivariate analysis of floral and vegetative traits revealed that there are at least two discrete morphological forms in the species complex. Field observations revealed that each form is pollinated by a different insect species, and thus represent distinct ecotypes. The early-flowering coastal form which has long spurs and floral scent dominated by sesquiterpene compounds is pollinated exclusively by the long-tongued bee Amegilla fallax (Apidae, Anthophorinae), while the late-flowering inland form with short spurs and floral scent dominated by benzenoid compounds is pollinated exclusively by the beetle Cyrtothyrea marginalis (Cetoniinae; Scarabaeidae). Choice experiments in a Y-maze olfactometer showed that beetles are preferentially attracted to the scent of the short-spurred form. A spur-shortening experiment showed that long spurs are required for effective pollination of the bee-pollinated form. Although it was initially thought likely that divergence occurred across a geographical pollinator gradient, plants of the long-spurred form were effectively pollinated when transplanted to an inland locality outside the natural coastal range of this form. Thus, the underlying geographical basis for the evolution of ecotypes in the E. parviflora complex remains uncertain, although early flowering in the long-spurred form to exploit the emergence of naïve bees may restrict this form to coastal areas where there is no frost that would damage flower buds. Later flowering of the short-spurred form coincides closely with the emergence of the pollinating beetles following winter frosts. This study identifies a shift between bee and beetle pollination as the main driver of floral divergence in an orchid species complex. Floral scent and spur length appear to be key traits in mediating this evolutionary transition.


Three-year safety and efficacy of vicriviroc, a CCR5 antagonist, in HIV-1-infected treatment-experienced patients.
Vicriviroc, an investigational CCR5 antagonist, demonstrated short-term safety and antiretroviral activity. Phase 2, double-blind, randomized study of vicriviroc in treatment-experienced subjects with CCR5-using HIV-1. Vicriviroc (5, 10, or 15 mg) or placebo was added to a failing regimen with optimization of background antiretroviral medications at day 14. Subjects experiencing virologic failure and subjects completing 48 weeks were offered open-label vicriviroc. One hundred eighteen subjects were randomized. Virologic failure (<1 log10 decline in HIV-1 RNA > or =16 weeks postrandomization) occurred by week 48 in 24 of 28 (86%), 12 of 30 (40%), 8 of 30 (27%), 10 of 30 (33%) of subjects randomized to placebo, 5, 10, and 15 mg, respectively. Overall, 113 subjects received vicriviroc at randomization or after virologic failure, and 52 (46%) achieved HIV-1 RNA <50 copies per milliliter within 24 weeks. Through 3 years, 49% of those achieving suppression did not experience confirmed viral rebound. Dual or mixed-tropic HIV-1 was detected in 33 (29%). Vicriviroc resistance (progressive decrease in maximal percentage inhibition on phenotypic testing) was detected in 6 subjects. Nine subjects discontinued vicriviroc due to adverse events. Vicriviroc seems safe and demonstrates sustained virologic suppression through 3 years of follow-up. Further trials of vicriviroc will establish its clinical utility for the treatment of HIV-1 infection.


Triple pelvic osteotomy for the management of painful developmental hip dysplasia in the young adult.
We present a consecutive series of 24 adolescent and young adult patients who have undergone a triple pelvic osteotomy as treatment for symptomatic developmental dysplasia of the hip. With a mean duration of follow-up of 6.5 years (range 2 -16 years) we report good improvements with regard to pain and function in 22 of the 24 patients. Radiological improvements were consistently demonstrated in the centre edge angle and the acetabular index. There were no major complications. When dealing with this difficult problem in young patients we maintain that a redirectional pelvic osteotomy is an appropriate means of treatment in symptomatic patients with a congruent joint.


Ovine model of neuropathic pain for assessing mechanisms of spinal cord stimulation therapy via dorsal horn recordings, von Frey filaments, and gait analysis.
It is becoming increasingly important to understand the mechanisms of spinal cord stimulation (SCS) in alleviating neuropathic pain as novel stimulation paradigms arise. Additionally, the small anatomic scale of current SCS animal models is a barrier to more translational research. Using chronic constriction injury (CCI) of the common peroneal nerve (CPN) in sheep (ovine), we have created a chronic model of neuropathic pain that avoids motor deficits present in prior large animal models. This large animal model has allowed us to implant clinical grade SCS hardware, which enables both acute and chronic testing using von Frey filament thresholds and gait analysis. Furthermore, the larger anatomic scale of the sheep allows for simultaneous single-unit recordings from the dorsal horn and SCS with minimal electrical artifact. Detectable tactile hypersensitivity occurred 21 days after nerve injury, with preliminary indications that chronic SCS may reverse it in the painful limb. Gait analysis revealed no hoof drop in the CCI model. Single neurons were identified and discriminated in the dorsal horn, and their activity was modulated via SCS. Unlike previous large animal models that employed a complete transection of the nerve, no motor deficit was observed in the sheep with CCI. To our knowledge, this is the first reported large animal model of chronic neuropathic pain which facilitates the study of both acute and chronic SCS using complementary behavioral and electrophysiologic measures. As demonstrated by our successful establishment of these techniques, an ovine model of neuropathic pain is suitable for testing the mechanisms of SCS.


Lactose tolerance in adult Jordanian Arabs.
Lactose tolerance tests were performed in 56 male and female Jordanian Arabs who were permanently resident in the Hashemite Kingdom of Jordan. Forty three had a low rise in blood glucose and 36 had one or more symptoms after oral lactose. Lactose tolerance was not related to sex, age, milk or milk products consumption. The data presented confirm the few existing reports that the majority of Arabs, originating from the Mediterranean basin are hypolactasic and intolerant to lactose.


A randomized comparison of patellar tendon and hamstring tendon anterior cruciate ligament reconstruction.
Patellar and hamstring tendon autografts are the most frequently used graft types for anterior cruciate ligament reconstruction, but few direct comparisons of outcomes have been published. There is no difference in outcome between the two types of reconstruction. Prospective randomized clinical trial. After isolated anterior cruciate ligament rupture, 65 patients were randomized to receive either a patellar tendon or a four-strand hamstring tendon graft reconstruction, and results were reviewed at 4, 8, 12, 24, and 36 months. Pain on kneeling was more common and extension deficits were greater in the patellar tendon group. There were greater quadriceps peak torque deficits in the patellar tendon group at 4 and 8 months but not thereafter. In the hamstring tendon group, active flexion deficits were greater from 8 to 24 months, and KT-1000 arthrometer side-to-side differences in anterior knee laxity at 134 N were greater. Cincinnati knee scores, International Knee Documentation Committee ratings, and rates of return to preinjury activity levels were not significantly different between the two groups. Both grafts resulted in satisfactory functional outcomes but with increased morbidity in the patellar tendon group and increased knee laxity and radiographic femoral tunnel widening in the hamstring tendon group.


Secondary structure of ribosomal RNA.
Infrared spectra were obtained for 16S and for 23S ribosomal RNA's in D(2)O solutions. The percentage of each base in the paired and unpaired regions of the RNA was determined from the spectra. The secondary structures of 16S and 23S ribosomal RNA's (from Escherichia coli) are significantly different from each other and are also different from those of yeast ribosomal RNA, formylmethionyl-transfer RNA, and the anticodon fragment of this transfer RNA.


Data fusion and 3D visualization for optimized representation of neurovascular relationships in the posterior fossa.
Reliable 3D visualization of neurovascular relationships in the posterior fossa at the surface of the brainstem is still critical due to artifacts of imaging. To assess neurovascular compression syndromes more reliably, a new approach of 3D visualization based on registration and fusion of high-resolution MR data is presented. A total of 80 patients received MRI data with 3D-CISS and 3D-TOF at 3.0 Tesla. After registration and subsequent segmentation, the vascular information of the TOF data was fused into the CISS data. Two 3D visualizations were created for each patient, one before and one after fusion, which were verified with the intraoperative situation during microvascular decompression (MVD). The reproduction quality of vessels was evaluated with a rating system. In all cases, the presented approach compensated for typical limitations in the 3D visualization of neurovascular compression such as the partial or complete suppression of larger vessels, suppression of smaller vessels at the CSF margin, and artifacts from heart pulsation. In more than 95% of the cases of hemifacial spasm and glossopharyngeal neuralgia, accurate assessment of the compression was only possible after registration and fusion. In more than 50% of the cases with trigeminal neuralgia, the presented approach was crucial to finding the actually offending vessel. 3D visualization of fused image data allows for a more complete representation of the vessel-nerve situation. The results from this approach are reproducible and the assessment of neurovascular compression is safer. It is a powerful tool for planning MVD.


Agonistic CD40 mAb-Driven IL12 Reverses Resistance to Anti-PD1 in a T-cell-Rich Tumor.
The durability and efficacy of anti-human PD1 monoclonal antibodies (PD1 mAb) vary across different malignancies. Although an absence of tumor-infiltrating cytotoxic T lymphocytes has been identified as a cause for resistance to PD1 mAb, the presence of intratumor exhausted PD1hi T cells also contributes to insensitivity to this immune checkpoint therapy. In this study, we used mouse tumor models of PD1 mAb resistance that harbored PD1hi T cells and flow cytometry analysis of tumor-infiltrating leukocytes immediately post-therapy as a screening platform to identify agents that could resensitize T cells to PD1 blockade. We showed that an agonistic anti-CD40 mAb converted PD1hi T cells into PD1lo T cells, reversing phenotypic T-cell exhaustion and allowing the anti-PD1 refractory tumors to respond to anti-PD1 therapy. PD1 downmodulation by anti-CD40 mAb relied upon IL12 but not IL23, CD80/CD86/CD28, or CD70/CD27. Consistent with a role for regulatory T cells (Treg) in promoting T-cell exhaustion, we also showed that intratumor Treg presented with a less activated and attenuated suppressive phenotype, marked by reductions in CTLA4 and PD1. Similar to anti-CD40 mAb, anti-CTLA4 mAb also lowered intratumor T-cell PD1 expression. Our study provides a proof-of-principle framework to systematically identify immune conditioning agents able to convert PD1hi T cells to PD1lo T cells, with clinical implications in the management of anti-PD1 refractory patients. Cancer Res; 76(21); 6266-77. ©2016 AACR.


[Pathogenesis of chronic disseminated acinar pulmonary tuberculosis: Oka's classification of pulmonary tuberculosis type IIB--a discussion through an analysis of two typical cases].
To elucidate the pathogenesis of chronic disseminated acinar pulmonary tuberculosis (Oka's classification type IIB). The subjects are two cases of chronic disseminated acinar pulmonary tuberculosis. The pathogenesis were discussed through an analysis of their radiologic findings on admission and in the past. Case 1 is a 36 year-old woman whose complaint was slight fever and cervical lymphadenopathy for past four months. Disseminated granular shadows were observed in both lung fields on the chest X-ray on admission. The CT examination indicated that each granule was composed of circumscribed lesion within terminal or respiratory bronchiole, so called acinar lesion. It is compatible with pulmonary tuberculosis type IIB according to Oka's classification. The bronchial lavage yielded Mycobacterium tuberculosis. When compared the chest X-ray with that at 4 months before, it is suggested that the granular lesions were first spread hematogeneously and each granule thereafter ruptured into the airway. Case 2 is a 90 year-old man with slight fever and weight loss. The chest X-ray showed diffuse granular shadows. The CT examination indicated that the lung shadows were composed of disseminated acinar lesions. The diagnosis of tuberculosis was established by a bronchoscopic examination. Comparison of the chest X-ray findings between those at 3 years 9 months before and 8 months before suggests the bronchogenic development of the disease. Through an analysis of these two cases, two kinds of pathogenesis were suggested in chronic disseminated acinar pulmonary tuberculosis; namely, one is hematogeneous route and the other is in bronchogenic route.


Multiscale Heterogeneous Polymer Composites for High Stiffness 4D Printed Electrically Controllable Multifunctional Structures.
4D printing is an emerging field where 3D printing techniques are used to pattern stimuli-responsive materials to create morphing structures, with time serving as the fourth dimension. However, current materials utilized for 4D printing are typically soft, exhibiting an elastic modulus (E) range of 10-4 to 10 MPa during shape change. This restricts the scalability, actuation stress, and load-bearing capabilities of the resulting structures. To overcome these limitations, multiscale heterogeneous polymer composites are introduced as a novel category of stiff, thermally responsive 4D printed materials. These inks exhibit an E that is four orders of magnitude greater than that of existing 4D printed materials and offer tunable electrical conductivities for simultaneous Joule heating actuation and self-sensing capabilities. Utilizing electrically controllable bilayers as building blocks, a flat geometry that morphs into a 3D self-standing lifting robot is designed and printed, setting new records for weight-normalized load lifted and actuation stress when compared to other 3D printed actuators. Furthermore, this ink palette is employed to create and print planar lattice structures that transform into various self-supporting complex 3D shapes. The contributions are integrated into a 4D printed electrically controlled multigait crawling robotic lattice structure that can carry 144 times its own weight.


Competitive and synergistic effects in pH dependent phosphate adsorption in soils: LCD modeling.
The pH dependency of soluble phosphate in soil was measured for six agricultural soils over a pH range of 3-10. A mechanistic model, the LCD (ligand charge distribution) model, was used to simulate this change, which considers phosphate adsorption to metal (hydr)oxides in soils under the influence of natural organic matter (NOM) and polyvalent cations (Ca(2+), Al(3+), and Fe(3+)). For all soils except one, the description in the normal pH range 5-8 is good. For some soils at more extreme pH values (for low P-loading soils at low pH and for high P-loading soils at high pH), the model over predicts soluble P. The calculation shows that adsorption is the major mechanism controlling phosphate solubility in soils, except at high pH in high P-loading soils where precipitation of calcium phosphate may take place. NOM and polyvalent cations have a very strong effect on the concentration level of P. The pattern of pH dependency of soluble P in soils differs greatly from the pH effects on phosphate adsorption to synthetic metal (hydr)oxides in a monocomponent system. According to the LCD model, the pH dependency in soil is mainly caused by the synergistic effects of Ca(2+) adsorption to oxides. Adsorption of Al(3+) to NOM adsorbed plays an important role only at a pH < 4.5. Presence of NOM coating strongly competes with phosphate for the adsorption and is an important factor to consider in modeling phosphate adsorption in natural samples.


Non-erosive and uncomplicated erosive reflux diseases: Difference in physiopathological and symptom pattern.
To investigate differences in the physiopathological findings (manometry and pH monitoring) and symptoms between cases of non-erosive reflux disease (NERD) and erosive reflux disease (ERD) found positive at 24 h pH monitoring. For a total of 670 patients who underwent 24 h pH monitoring, esophageal manometry and upper endoscopy were retrospectively evaluated, assessing the reflux symptoms, manometric characteristics of the lower esophageal sphincter (LES) and esophageal body and the presence or absence of esophagitis and hiatal hernia. Typical and atypical symptoms were also evaluated. For inclusion in the study, patients had to have NERD or ERD and be found positive on pH monitoring (NERD+). Patients with Gastroesophageal reflux disease (GERD) complicated by stenosis, ulcers or Barrett's esophagus were ruled out. 214 patients were involved in the study, i.e. 107 cases of NERD+ and 107 of ERD. There were no significant gender- or age-related differences between the two groups. The ERD group had more cases of hiatal hernia (P = 0.02) and more acid reflux, both in terms of number of reflux episodes (P = 0.01) and as a percentage of the total time with a pH < 4 (P = 0.00), when upright (P = 0.007) and supine (P = 0.00). The NERD+ cases had more reflux episodes while upright (P = 0.02) and the ERD cases while supine (P = 0.01). The LES pressure was higher in cases of NERD+ (P = 0.03) while the amplitude and duration of their esophageal peristaltic waves tended to be better than in the ERD group (P >0.05). The NERD+ patients presented more often with atypical symptoms (P = 0.01). The NERD+ patients' fewer reflux episodes and the fact that they occurred mainly while in the upright position (unlike the cases of ERD) may be two factors that do not favor the onset of esophagitis. The frequently atypical symptoms seen in patients with NERD+ need to be accurately evaluated for therapeutic purposes because patients with GERD and atypical symptoms generally respond only partially to medical and surgical treatments.


Hemagglutinin-esterase, a novel structural protein of torovirus.
We have characterized the 3'-most 3 kb of the genome of bovine torovirus (BoTV) strain Breda. A novel 1.2-kb gene, located between the genes for the membrane and nucleocapsid proteins, was identified. This gene, the 3'-most 0.5 kb of which is also present in the genome of the equine torovirus isolate Berne virus (BEV), codes for a class I membrane protein displaying 30% sequence identity with the hemagglutinin-esterases (HEs) of coronaviruses and influenza C viruses. Heterologous expression of the BoTV HE gene yielded a 65,000-molecular weight N-glycosylated protein displaying acetylesterase activity. Serologic evidence indicates that the HE homolog is expressed during the natural infection and represents a prominent antigen. By using an antiserum raised against residues 13 to 130 of HE, the HE protein was detected in radioiodinated, sucrose gradient-purified BoTV preparations. Formal evidence that HE is a structural protein was provided by immunoelectron microscopy. In addition to the large, 17- to 20-nm spikes, BoTV virions possess shorter surface projections (6 nm on average). We postulate that these surface projections, which are absent from the BEV virion, are composed of the BoTV HE homolog. The HE gene, which has now been demonstrated in three different virus genera, is a showpiece example of modular evolution.


Investigation of the Antibacterial Properties of Silver-Doped Amorphous Carbon Coatings Produced by Low Pressure Magnetron Assisted Acetylene Discharges.
Hospital-acquired infections are responsible for a significant part of morbidity and mortality. Among the possible modes of transmission, this study focuses on environmental surfaces by developing innovative antibacterial coatings that can be applied on interior fittings in hospitals. This work aims to optimize a coating made of an amorphous carbon matrix doped with silver (a-C:H:Ag) produced by a hybrid PVD/PECVD process and to evaluate its antibacterial activity. We present a coating characterization (chemical composition and morphology) as well as its stability in an ageing process and after multiple exposures to bacteria. The antibacterial activity of the coatings is demonstrated against Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive) bacteria through several bioassays. Moreover, the data suggest a crucial role of silver diffusion towards the surface and nanoparticle formation to explain the very promising anti-bacterial activities reported in this work.


Comparison of glycosphingolipids and antibodies as receptor molecules for ricin detection.
Glycosphingolipids (GSLs) have been shown to undergo strong interactions with a number of protein toxins, including potential bioterrorism agents such as ricin and botulinum neurotoxin. Characterization of this interaction in recent years has led to a number of studies where GSLs were used as the recognition molecules for biosensing applications. Here, we offer a comparison of quartz crystal microbalance (QCM) sensors for the detection of ricin using antibodies and the GSLs GM1 and asialoGM1, which have been shown to undergo strong interactions with ricin. The presence, orientation, and activity of the GSL and antibody films were confirmed using ellipsometry, Fourier transform infrared spectroscopy (FT-IR), and QCM. It was found that the GSLs offered more sensitive detection limits when directly compared with antibodies. Both GSLs had lower detection limits at 5 microg/mL, approximately 5 times lower than were found for antibodies (25 microg/mL), and their linear detection range extended to the highest concentrations tested (100 microg/mL), almost an order of magnitude beyond the saturation point for the antibody sensors. Potential sites for nonspecific adsorption were blocked using serum albumin without sacrificing toxin specificity.


The articulatory in-out effect resists oral motor interference.
People prefer words with inward directed consonantal patterns (e.g., MENIKA) compared to outward patterns (KENIMA), because inward (outward) articulation movements resemble positive (negative) mouth actions such as swallowing (spitting). This effect might rely on covert articulation simulations, or subvocalizations, since it occurs also under silent reading. We tested to what degree these underlying articulation simulations are disturbed by oral motor interference. In 3 experiments (total N = 465) we interfered with these articulation simulations by employing concurrent oral exercises that induce oral motor noise while judging inward and outward words (chewing gum, Experiment 1; executing meaningless tongue movements, Experiment 2; concurrent verbalizations, Experiment 3). Across several word stimulus types, the articulatory in-out effect was not modulated by these tasks. This finding introduces a theoretically interesting case, because in contrast to many previous demonstrations regarding other motor-preference effects, the covert simulations in this effect are not susceptible to selective motor interference. (PsycINFO Database Record


A meta-analysis of tea drinking and risk of Parkinson's disease.
Many studies have reported an association between tea drinking and Parkinson's disease (PD). Our purpose is to summarize the available information and evaluate the risk of PD associated with tea drinking. We searched all publications in English language on the association of tea drinking and PD risk published up to December 2010. The pooled analysis was performed with Review Manager 5.0. In total, eight articles including 1418 cases and 4250 controls were included in the meta-analysis. The pooled odds ratio (95% CI) was 0.85 (0.74-0.98), which suggests the protective effect of tea drinking in PD risks. Moreover, the summary OR (OR: 0.83, 95% CI = 0.69-0.99) for drinkers of ≤ 1 cup of tea per day versus nonconsumers and that (OR: 0.96, 95% CI = 0.73-1.27) for drinkers of >1 cups of tea per day versus nonconsumers showed that there was not an apparent dose-response relationship. No indication for publication bias was found. This meta-analysis showed that tea drinking can lower the risk of PD, while no apparent dose-response relationship was found. Further effort is needed to fully understand the mechanism underlying the beneficial effect of tea consumption in lowering PD risk.


Thermal Monitoring of Tumor and Tissue State during Radiation Therapy - A Complex Case of Radiation Recall.
Common radiation dermatitis over radiation fields can be mild as minor erythema but can also be associated with blisters and skin desquamation. This phenomenon has been widely investigated and documented, especially in breast cancer patients. Obesity, smoking, and diabetes are known risk factors; however, we cannot predict the severity of radiation dermatitis prior to treatment. The overwhelming radiation recall dermatitis is an acute inflammatory reaction confined to previously irradiated areas that can be triggered when chemotherapy agents are administered after radiotherapy. This rare, painful skin reaction leads to treatment cessation or alteration. In this study, we investigate the feasibility of using thermography as a tool to predict the response of normal breast tissue and skin to radiation therapy and the risk of developing radiation recall dermatitis. Six women with viable in-breast tumor (breast cancer) and eight women who underwent tumor resection (lumpectomy) were monitored by a thermal camera prior to radiotherapy treatment (breast region) and on weekly basis, in the same environmental conditions, through the radiation course of treatment. One patient developed radiation recall dermatitis when treated with chemotherapy following radiation therapy, and needed intensive local treatments and narcotics with full recovery thereafter. Clinical and treatment data as well as response to radiation were collected prospectively. The ongoing thermal changes observed during the radiation treatment for all patients, with and without viable tumor in the breast, were documented, analyzed, and reported here with detailed comparison to the recognized data for the patient diagnosed with radiation recall dermatitis.


The effect of drastic temperature changes on the performance of MBR treating municipal wastewater.
A study has been carried out to define the effect of drastic temperature changes on the performance of lab-scale hollow-fibre MBR in treating municipal wastewater at a flux of 10 L m(-2) h(-1) (LMH). The objectives of the study were to estimate the activated sludge properties, the removal efficiencies of COD and NH(3)-N and the membrane fouling tendency under critical conditions of drastic temperature changes (23, 33, 42 & 33 °C) and MLSS concentration ranged between 6,382 and 8,680 mg/L. The study exhibited that the biomass reduction, the low sludge settleability and the supernatant turbidity were results of temperature increase. The temperature increase led to increase in SMP carbohydrate and protein, and to decrease in EPS carbohydrate and protein. The BRE of COD dropped from 80% at 23 °C to 47% at 42 °C, while the FRE was relatively constant at about 90%. Both removal efficiencies of NH(3)-N trended from about 100% at 33 °C to less than 50% at 42 °C. TMP and BWP ascended critically with temperature increase up to 336 and 304 mbar respectively by the end of the experiment. The values of suspended solids (SS) and the turbidity in the final effluent were negligible. The DO in the mixed liquor was varying with temperature change, while the pH was within the range of 6.7-8.3.


Endoscopic placement of the capsule endoscope in children.
Capsule endoscopy provides a minimally invasive examination of the entire small bowel. However, some children and disabled adults may be unable to independently ingest the capsule. A new method for endoscopic placement of the capsule endoscope is described. Consecutive children who required capsule endoscopy of the small bowel and who were unable to independently ingest the capsule were selected for endoscopic placement. A net retrieval catheter and a translucent ligation adaptor were used to hold and stabilize alignment of the capsule during endoscopic insertion into the distal duodenum. Eleven pediatric patients underwent successful endoscopic placement of a capsule endoscope in the duodenum without complication. One capsule migrated back into the stomach, where it remained for the life of the battery. Endoscopic placement of the capsule endoscope by using the described technique appears to be effective and safe. It facilitates capsule endoscopy in patients who are unable to independently ingest the capsule.


Blockade of dengue virus infection and viral cytotoxicity in neuronal cells in vitro and in vivo by targeting endocytic pathways.
Dengue virus (DENV) infection in neuronal cells was speculated to trigger neuropathy. Herein, we determined the blockade of DENV infection by targeting endocytic pathways in vitro and in vivo. In DENV-infected mouse brains, we previously showed that viral proteins are expressed in neuronal cells around the hippocampus with accompanying neurotoxicity. DENV caused infection, including entry, double-stranded (ds)RNA replication, protein expression, and virus release, followed by cytotoxicity in the mouse neuronal Neuro-2a cell line. Pharmacologically blocking clathrin-mediated endocytosis of the DENV retarded viral replication. Targeting vacuolar-type H+-ATPase (V-ATPase)-based endosomal acidification effectively blocked the DENV replication process, but had no direct effect on viral translation. Blockade of the clathrin- and V-ATPase-based endocytic pathways also attenuated DENV-induced neurotoxicity. Inhibiting endosomal acidification effectively retarded DENV infection, acute viral encephalitis, and mortality. These results demonstrate that clathrin mediated endocytosis of DENV followed by endosomal acidification-dependent viral replication in neuronal cells, which can lead to neurotoxicity.


Cytodiagnosis of a Cutaneous Clear Cell Malignancy: Metastatic Renal Cell Carcinoma on Chin.
Clear cell type of renal cell carcinoma (RCC) is most common urological malignancy. Several diagnostic challenges arise when it presents as a cutaneous nodule, being an uncommon presentation. Fine needle aspiration cytology (FNAC) of a cutaneous nodule is crucial for distinguishing primary tumours from metastatic tumours because cutaneous metastases represent a terminal stage of illness. Due to considerable overlap of cytomorphological features determination of primary warrants need of detailed clinical history and close inspection of every cytological detail. We report here a case of cutaneous metastasis of RCC on chin in a patient 11 years after nephrectomy. Though there are reports of RCC metastases diagnosed on histology, there are fewer cytology case reports. Cytological differential diagnosis has been discussed for arriving at the final diagnosis in case of clear cell tumours. Early and accurate diagnosis is mandatory for optimal treatment. Cytodiagnosis of cutaneous metastasis of RCC is uncommon due to its low suspicion index in cutaneous nodules. More so, it presents late and an unusual sites due to its resemblance to common dermatological diseases.


Oncotype Dx assay and breast cancer in the United States: usage and concordance with chemotherapy.
The 21-gene recurrence score (RS) assay (Oncotype DX™) predicts the likelihood of breast cancer recurrence and chemotherapy responsiveness. The aims of this study were to describe temporal trends in assay usage, to investigate factors associated with the receipt of the assay and to determine how the assay is associated with treatment decisions. Random samples of stage I-II female breast cancer patients diagnosed in 2004, 2005 and 2010 as reported to the National Cancer Institute's Surveillance Epidemiology and End Results program were included. Among women diagnosed in 2010 with estrogen receptor positive (ER+), lymph node-negative (LN-) tumors, factors associated with receipt of the assay were identified and the likelihood of chemotherapy by RS was estimated. Assay usage increased over time (ER+/LN-:8.0-27.0 %, p < 0.01; ER+/LN+: 2.0-15.7 %, p = 0.09; ER-: 0.2-1.7 %, p < 0.01) from 2005 to 2010. Receipt of the assay was associated with younger age, lower area income and tumor characteristics. Among women in the low (RS < 18) and high risk (RS > 30) categories, 3.3 and 95.9 % received chemotherapy, respectively. Within the intermediate risk group the receipt of chemotherapy varied: 12.8 % (RS: 18-19), 35.0 % (RS: 20-23) and 84.0 % (RS: 24-30). During the study years, assay usage increased among women for whom the assay is and is not guideline recommended. Factors such as insurance and race/ethnicity do not appear to be associated with the receipt of the assay. The RS, as determined broadly via three categories and within the intermediate risk group, does appear to influence chemotherapy decisions.


Prevalence of atrial fibrillation in China and its risk factors.
To study the prevalence of atrial fibrillation (AF) and the relation with its risk factors in China. A total of 19 363 participants (8635 males and 10 728 females) aged ⋝35 years in geographically dispersed urban and rural regions of China were included in this cross-sectional survey. All participants received questionnaire, physical and blood examination. Echocardiography were performed for AF patients found in the survey. Of the 19 363 participants, 199 were diagnosed with AF. The estimated age-standardized prevalence of AF was 0.78% in men and 0.76% in women. The prevalence of AF in participants aged <60 years was 0.41% in men and 0.43% in women, and was 1.83% in both men and women aged ⋝60 years. About 19.0% of males and 30.9% of females with AF were diagnosed with valve disease. Age- and sex-adjusted multivariable logistic regression analysis revealed that myocardial infarction, left ventricular hypertrophy (LVH), obesity, and alcohol consumption were associated with a increased risk of AF(P<0.05). The age standardized prevalence of AF is 0.77% in the participants enrolled in the present study. The number of AF cases aged ⋝35 years is 5.26 million according to 2010 Chinese Census. Most risk factors for AF, identified mainly in Western countries, are also detected in China.


Chromatin jets define the properties of cohesin-driven in vivo loop extrusion.
Complex genomes show intricate organization in three-dimensional (3D) nuclear space. Current models posit that cohesin extrudes loops to form self-interacting domains delimited by the DNA binding protein CTCF. Here, we describe and quantitatively characterize cohesin-propelled, jet-like chromatin contacts as landmarks of loop extrusion in quiescent mammalian lymphocytes. Experimental observations and polymer simulations indicate that narrow origins of loop extrusion favor jet formation. Unless constrained by CTCF, jets propagate symmetrically for 1-2 Mb, providing an estimate for the range of in vivo loop extrusion. Asymmetric CTCF binding deflects the angle of jet propagation as experimental evidence that cohesin-mediated loop extrusion can switch from bi- to unidirectional and is controlled independently in both directions. These data offer new insights into the physiological behavior of in vivo cohesin-mediated loop extrusion and further our understanding of the principles that underlie genome organization.


[Combined reconstructive hernioplasty for small and middle-size hernia of the abdominal wall].
The results of prosthetic hernioplasty, performed in 61 patients for a small- and middle-size abdominal wall hernia (AWH) were analyzed. In a control group in 18 (29.5%) patients the IPOM-procedure was applied and in the main group in 43 (70.5%)--the combined plasty. Complications, which have had occurred in 2 (11.1%) patients of a control group and in 4 (9.3%)--of the main, were cured using conservative methods. While five-year followup the AWH recurrence was not noted. The introduction of the elaborated tactic of treatment, named the combined reconstructive hernioplasty, have permitted to improve the late functional and cosmetic results due to restoration of abdominal linea alba integrity.


Antimicrobial susceptibility profile, treatment outcome and serotype distribution of clinical isolates of Salmonella enterica subspecies enterica: a 2-year study from Kerala, South India.
Typhoid and paratyphoid fever continue to be important causes of illness and death in parts of Asia, being associated with poor sanitation and consumption of unsafe food and water. Antimicrobial resistance has emerged to traditional first-line drugs, namely, the fluoroquinolones, as well as to third-generation cephalosporins, posing challenges to treatment. Azithromycin has proven to be an effective alternative for treatment of uncomplicated typhoid fever. The purpose of this study was to determine the antimicrobial susceptibility, clinical outcome and serotype distribution pattern of clinical isolates belonging to Salmonella enterica subspecies enterica. All clinical isolates of S. enterica obtained from blood, sterile body fluids, as well as stool and urine samples at Amrita Institute of Medical Sciences and Research Centre, Kerala, India, between August 2011 and July 2013 were included in the study and processed based on standard microbiology protocols. A total of 118 isolates of Salmonella were obtained during the study period. Out of these, 79 were of S. Typhi (66.95%), followed by isolates of S. Paratyphi A (22; 18.64%) and S. Typhimurium 12 (10.17%). Five isolates could not be identified further. There was 100% susceptibility to ceftriaxone in all S. enterica subspecies. Ciprofloxacin susceptibility was 32.91% for S. Typhi and 40.90% for S. Paratyphi A as determined by the disk diffusion method. The susceptibility profile of S. Typhi isolates to different antimicrobials was as follows: chloramphenicol (94.93%), ampicillin (77.21%), cotrimoxazole (75.94%) and azithromycin (78.48%). For S. Typhi, the minimum inhibitory concentration (MIC) of ciprofloxacin required to inhibit the growth of 50% of organisms was 0.5 μg/mL (intermediate) and MIC required to inhibit the growth of 90% of organisms was 1 μg/mL (resistant). S. Typhimurium was 100% susceptible to cotrimoxazole, ampicillin, ceftriaxone, chloramphenicol, ofloxacin and azithromycin. Susceptibility to ciprofloxacin was 66.66%. Patients from whom S. Typhimurium was isolated had comorbidities with documented risk. Of the 118 patients, 3 expired. Two had typhoid fever and were in sepsis at admission. One had S. Typhimurium and was suffering from multiple myeloma. S. Typhi was the predominant isolate. All isolates were susceptible to ceftriaxone. Chloramphenicol susceptibility was >90%. No multidrug-resistant Salmonella strains were isolated. Susceptibility to ciprofloxacin for S. Typhi was 33%. Recovery rate was 97%.


Dermatology referrals in the hospital setting.
Dermatology consultation occurs mainly in the outpatient setting. The reasons for inpatient dermatologic consultation by other specialties in a hospital, its frequency and its impact on health care are largely unrecorded. We retrospectively studied the records of 971 hospitalized patients or patients being evaluated in emergency services for which a dermatologist's consultation was requested over a 5-year period in a medium sized military hospital. The demographic details, specialties requiring consultation, provisional diagnosis and dermatological investigations done were tabulated. Dermatologic consultation changed the dermatologic diagnosis and treatment in more than 2/3rd of the patients. Generally, the dermatologic diagnoses most frequently missed by the referring service were common conditions with established treatment. The overall impact of dermatologic consultation on health delivery to patients was substantial. Important recommendations to any health care system are offered.


The expression of anger and its relationship to symptoms and cognitions in obsessive-compulsive disorder.
We compared the association between obsessive-compulsive disorder (OCD) and the expression of anger in a sample of 71 patients and 71 college students. Some authors [Rubenstein et al., J Anxiety Disord 1995;9:1-9] have proposed that anger and hostility underlie the symptoms of OCD; however, there has been little empirical study of this relationship. One recent study [Whiteside and Abramowitz, Cog Therapy Res 2004;28:259-268] with college undergraduates found that the association between OCD symptoms and anger was attributable to depressive symptoms. In the present study, we compared the expression of anger in a sample of patients diagnosed with OCD and nonclinical volunteers. Consistent with the previous study, we found increased levels of anger in patients with OCD as compared to control participants; however, these differences could be attributed to between-group differences in general distress. These results were discussed within the framework of the cognitive theory of OCD.


Enhanced spontaneous retrieval of cues from emotional events: An ERP study.
Recent evidence points to enhanced episodic memory retrieval not only for emotional items but also for neutral information encoded in emotional contexts. However, prior research only tested instructed explicit recognition, and hence here we investigated whether memory retrieval is also heightened for cues from emotional contexts when retrieval is not explicitly probed. During the first session of a two-session experiment, neutral objects were presented on different background scenes varying in emotional and neutral contents. One week later, objects were presented again (with no background) intermixed with novel objects. In both sessions, participants were instructed to attentively watch the stimuli (free viewing procedure), and during the second session, ERPs were also collected to measure the ERP Old/New effect, an electrophysiological correlate of episodic memory retrieval. Analyses were performed using cluster-based permutation tests in order to identify reliable spatio-temporal ERP differences. Based on this approach, old relative to new objects, were associated with larger ERP positivity in an early (364-744 ms) and late time window (760-1148 ms) over distinct central electrode clusters. Interestingly, significant late ERP Old/New differences were only observed for objects previously encoded with emotional, but not neutral scenes (504 to 1144 ms). Because these ERP differences were observed in a non-instructed retrieval context, our results indicate that long-term, spontaneous retrieval for neutral objects, is particularly heightened if encoded within emotionally salient contextual information. These findings may assist in understanding mechanisms underlying spontaneous retrieval of emotional associates and the utility of ERPs to study maladaptive involuntary memories in trauma- and stress-related disorders.


GABA uptake by human blood platelets: effects of lithium and rubidium chlorides.
The methodologic and kinetic characteristics of GABA uptake by platelets were determined in blood platelets of volunteer donors. Extrapolation of a reciprocal plot indicate two uptake systems: a high affinity and a passive diffusion mechanism. When LiCl and RbCl were added in vitro, they had no effect on platelet GABA uptake. Our data suggest that platelet GABA and 5-HT uptake are carried out by different systems.


A Digital Counselor-Delivered Intervention for Substance Use Among People With HIV: Development and Usability Study.
Substance use disorders are prevalent and undertreated among people with HIV. Computer-delivered interventions (CDIs) show promise in expanding reach, delivering evidence-based care, and offering anonymity. Use in HIV clinic settings may overcome access barriers. Incorporating digital counselors may increase CDI engagement, and thereby improve health outcomes. We aim to develop and pilot a digital counselor-delivered brief intervention for people with HIV who use drugs, called "C-Raven," which is theory grounded and uses evidence-based practices for behavior change. Intervention mapping was used to develop the CDI including a review of the behavior change research in substance use, HIV, and digital counselors. We conducted in-depth interviews applying the situated-information, motivation, and behavior skills model and culturally adapting the content for local use with people with HIV. With a user interaction designer, we created various digital counselors and CDI interfaces. Finally, a mixed methods approach using in-depth interviews and quantitative assessments was used to assess the usability, acceptability, and cultural relevance of the intervention content and the digital counselor. Participants found CDI easy to use, useful, relevant, and motivating. A consistent suggestion was to provide more information about the negative impacts of drug use and the interaction of drug use with HIV. Participants also reported that they learned new information about drug use and its health effects. The CDI was delivered by a "Raven," digital counselor, programmed to interact in a motivational interviewing style. The Raven was perceived to be nonjudgmental, understanding, and emotionally responsive. The appearance and images in the intervention were perceived as relevant and acceptable. Participants noted that they could be more truthful with a digital counselor, however, it was not unanimously endorsed as a replacement for a human counselor. The C-Raven Satisfaction Scale showed that all participants rated their satisfaction at either a 4 (n=2) or a 5 (n=8) on a 5-point Likert scale and all endorsed using the C-Raven program again. CDIs show promise in extending access to care and improving health outcomes but their development necessarily requires integration from multiple disciplines including behavioral medicine and computer science. We developed a cross-platform compatible CDI led by a digital counselor that interacts in a motivational interviewing style and (1) uses evidence-based behavioral change methods, (2) is culturally adapted to people with HIV who use drugs, (3) has an engaging and interactive user interface, and (4) presents personalized content based on participants' ongoing responses to a series of menu-driven conversations. To advance the continued development of this and other CDIs, we recommend expanded testing, standardized measures to evaluate user experience, integration with clinician-delivered substance use treatment, and if effective, implementation into HIV clinical care.


Hydroalcoholic extract based-ointment from Punica granatum L. peels with enhanced in vivo healing potential on dermal wounds.
The present study reports for the first time, the in vivo wound healing potential of Punica granatum L. peels. A 5% (w/w) methanolic extract based-ointment was formulated and evaluated for its wound healing in guinea pigs. The ointment was applied in vivo on the paravertebral area of twelve excised wounded models once a day for 10 consecutive days. The ointment significantly enhanced the wound contraction and the period of epithelialization as assessed by the mechanical (contraction rate, tensile strength), the biochemical (increasing of collagen, DNA and proteins synthesis) and the histopathological characteristics. Such investigation was encouraged by the efficiency of the methanolic extract as antimicrobial and antioxidant. Indeed, the extract showed antioxidant activity as strong as natural and synthetic compounds (Trolox, BHA, Quercetin). Furthermore, the extract exhibited significant antibacterial and antifungal activity against almost all tested bacteria: Pseudomonas aeruginosa ATCC 9027, Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Klebsiella pneumoniae, Salmonella anatum, Salmonella typhimurium, Streptococcus pneumoniae, and fungi Candida albicans, Candida glabrata, Trichopyton rubrum and Aspergillus niger. The formulated ointment might well find use as skin repair agent without hazard to human health based on these results and on the fact that it has been well established that the extracts of pomegranate used in conditions similar to those applied by traditional medicine, showed no toxic effects.


Ovule Gene Expression Analysis in Sexual and Aposporous Apomictic Hypericum perforatum L. (Hypericaceae) Accessions.
Hypericum perforatum L. (2n = 4x = 32) is an attractive model system for the study of aposporous apomixis. The earliest phenotypic features of aposporous apomixis in this species are the mitotic formation of unreduced embryo sacs from a somatic cell of the ovule nucellus and the avoidance of meiosis. In this research we addressed gene expression variation in sexual and apomictic plants, by focusing on the ovule nucellus, which is the cellular domain primarily involved into the differentiation of meiocyte precursors and aposporous embryo sacs, at a pre-meiotic developmental stage. Gene expression analyses performed by RNAseq identified 396 differentially expressed genes and 1834 transcripts displaying phenotype-specific expression. Furthermore, the sequencing and assembly of the genome from a diploid sexual accession allowed the annotation of a 50 kb sequence portion located upstream the HAPPY locus and to address the extent to which single transcripts were assembled in multiple variants and their co-expression levels. About one third of identified DEGs and phenotype-specific transcripts were associated to transcript variants with alternative expression patterns. Additionally, considering DEGs and phenotype-specific transcript, the co-expression level was estimated in about two transcripts per locus. Our gene expression study shows massive differences in the expression of several genes encoding for transposable elements. Transcriptional differences in the ovule nucellus and pistil terminal developmental stages were also found for subset of genes encoding for potentially interacting proteins involved in pre-mRNA splicing. Furthermore, the sexual and aposporous ovule transcriptomes were characterized by differential expression in genes operating in RNA silencing, RNA-mediated DNA methylation (RdDM) and histone and chromatin modifications. These findings are consistent with a role of these processes in regulating cell fate determination in the ovule, as indicated by forward genetic studies in sexual model species. The association between aposporous apomixis, pre-mRNA splicing and DNA methylation mediated by sRNAs, which is supported by expression data and by the enrichment in GO terms related to these processes, is consistent with the massive differential expression of multiple transposon-related sequences observed in ovules collected from both sexual and aposporous apomictic accessions. Overall, our data suggest that phenotypic expression of aposporous apomixis is concomitant with the modulation of key genes involved in the two interconnected processes: RNA splicing and RNA-directed DNA methylation.


Transurethral microwave thermotherapy for symptomatic benign prostatic hyperplasia: short-term experience with Prostcare.
To assess our short-term experience with transurethral microwave thermotherapy (TUMT) for symptomatic benign prostatic hyperplasia (BPH). From August 1993 through July 1994, in total 65 patients with symptomatic BPH were enrolled into this study. The patients' ages ranged from 56 to 95 years with a mean of 70 years. Under local anesthesia with intraurethral instillation of Xylocaine jelly only, all patients received one session of TUMT for up to 60 min with Prostcare equipment. Uroflowmetry was performed and international prostatic symptom score (IPSS) determined before 3 and 6 months after TUMT for assessment of efficacy. All adverse events were recorded and evaluated for clinical relevance. At 3 and 6 months following TUMT, the mean IPSS decreased from 19.7 +/- 6.8 (baseline) to 12.8 +/- 8.2 (-46%) and to 15.5 +/- 9.0 (-21%), respectively; the maximal urine flow rate at 3 and 6 months increased from 9.1 +/- 4.8 ml/s (baseline) to 11.0 +/- 4.9 ml/s (+21%) and to 10.9 +/- 5.6 ml/s (+19%), respectively. During TUMT, burning sensation was the most frequent complaint (38.5%), followed by urethral discomfort (29.2%) and urgency (9.2%). Two patients (3.1%) interrupted TUMT, because of intolerable pain. Following TUMT micturition pain (73.8%) and gross hematuria (45.9%) were the most adverse events. Most of these adverse events disappeared within 2 weeks. One patient suffered from skin erosion over the penoscrotal junction 1 week later. None had retrograde ejaculation; 1 patient complained of erectile dysfunction. Although the efficacy of TUMT with Prostcare became less prominent 6 months after TUMT, TUMT was still a tolerable, safe alternative treatment of BPH, especially in patients who were not suitable for transurethral resection of the prostate or anesthesia.


Examination of inequalities in HIV/AIDS mortality in the United States from a fundamental cause perspective.
We examined changes in socioeconomic status (SES) and Black to White inequalities in HIV/AIDS mortality in the United States before and after the introduction of highly active antiretroviral therapy (HAART). Taking a fundamental cause perspective, we used negative binomial regression to analyze trends in county-level gender-, race-, and age-specific HIV/AIDS mortality rates among those aged 15 to 64 years during the period 1987-2005. Although HIV/AIDS mortality rates decreased once HAART became available, the declines were not uniformly distributed among population groups. The associations between SES and HIV/AIDS mortality and between race and HIV/AIDS mortality, although present in the pre-HAART period, were significantly greater in the peri- and post-HAART periods, with higher SES and White race associated with the greatest declines in mortality during the post-HAART period. Our findings support the fundamental cause hypothesis, as the introduction of a life-extending treatment exacerbated inequalities in HIV/AIDS mortality by SES and by race. In addition to a strong focus on factors that improve overall population health, more effective public health interventions and policies would facilitate an equitable distribution of health-enhancing innovations.


Survey of scholastic athletic health care and sports medicine clinics.
The increasing number of athletes requiring health care has spurred the growth of the development of sports medicine clinics. The diversity of such clinics is readily apparent. These clinics primarily function to provide evaluative and rehabilitative measures to all groups of athletic participants. Scholastic health care for athletic participants has not proceeded in a similar pattern. Sports medicine clinics are not effectively meeting the needs of the scholastic athlete, primarily because of location and financial limitations. This survey was conducted to collect information to further delineate the problems associated with scholastic health care of athletic participants. It appears that sports medicine clinics are manned by several levels of health care professionals. Scholastic athletes are least adequately covered by insurance and also suffer from being within a somewhat isolated environment. The need for on-field care and follow-up care within the school system remains a key problem associated with scholastic health care. Further research into the relationship of insurance policies which will adequately meet the needs of the scholastic population must be pursued. J Orthop Sports Phys Ther 1983;5(2):78-81.


Reevaluation of the effect of mouse mammary tumor virus infection on the BALB/c mouse hyperplastic outgrowth.
The BALB/c (C-) mouse hyperplastic outgrowth line (D1) was used to study murine mammary tumor virus (MuMTV) expression in both D1 and tumors derived from D1. D1 was transplanted into virus-infected BALB/cfC3H (C+) and virus-uninfected C- animals. In duplicate studies, tumor incidence was the same in both groups. However, the tumor latency period was longer for D1 transplanted into C+ mice (D1/C+) than for D1 transplanted into C- mice (D1/C-). MuMTV was detected in 85% of D1/C+ outgrowths and in 29% of D1/C+ tumors but was never detected in D1/C- outgrowths or tumors. D1/C- outgrowth and tumors and most of the D1/C+ tissues expressed little or no MuMTV RNA. Some D1/C+ tumors expressed substantial levels of MuMTV RNA. These same tumors also had MuMTV antigen and contained the exogenously acquired C3H-MuMTV provirus in the cellular DNA as shown by DNA fragment patterns following cleavage with Pst I and Eco RI endonucleases. D1/C+ tumors containing no viral RNA were also antigen-negative and lacked the acquired C3H provirus. These studies indicate that D1 has substantially changed in its incidence and in its response to MuMTV. MuMTV infection was not tumorigenic in the traditional sense, a finding that has led to a reevaluation of our current models of virus-host relationships and the biology of precancerous conditions.


Reproxalap Improves Signs and Symptoms of Allergic Conjunctivitis in an Allergen Chamber: A Real-World Model of Allergen Exposure.
To assess the prophylactic and treatment activity of reproxalap, a novel reactive aldehyde species inhibitor, in a real-world model of allergen exposure. In a randomized, double-masked, vehicle-controlled, crossover Phase 2 trial, 70 adult patients with ≥2 years of moderate to severe allergic conjunctivitis history, a positive skin test to ragweed pollen, and allergen chamber-induced ocular itching and redness scores of ≥2.5 and ≥2 (both scales range from 0 to 4), respectively, were randomized 1:1:1 to one of three sequences: 0.25% reproxalap, 0.5% reproxalap, and placebo; 0.5% reproxalap, placebo, and 0.25% reproxalap; or placebo, 0.25% reproxalap, and 0.5% reproxalap. Symptoms and conjunctival redness were assessed over 3.5 hours in an allergen chamber of aerosolized ragweed pollen (3500 grains/m3). Test article was administered bilaterally just before chamber entry and at 90 minutes after chamber entry. Reproxalap was safe and well tolerated; 66 of 70 enrolled patients completed all visits. Relative to vehicle, both concentrations of reproxalap demonstrated statistically significant and clinically relevant improvements in ocular itching, tearing, and redness over the duration of exposure in the chamber (P < 0.001 for all assessments). Prophylactic and treatment activity of drug were demonstrated. In an allergen chamber, reproxalap, a novel reactive aldehyde species inhibitor, was statistically superior to vehicle across the typical symptoms and signs of allergic conjunctivitis. These data are among the first rigorous clinical results demonstrating drug improvement in allergic conjunctivitis in an allergen chamber, a real-world model of allergen exposure.


Spongiibacterium pacificum sp. nov., isolated from seawater of South Pacific Gyre and emended description of the genus Spongiibacterium.
A Gram-stain-negative, strictly aerobic, non-flagellated, non-gliding, oxidase-positive and yellow-pigmented rod-shaped bacterium, designated strain SW169(T), was isolated from a surface seawater sample collected from the South Pacific Gyre (27° 55' S 123° 10' W) during the Integrated Ocean Drilling Program (IODP) Expedition 329. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain SW169(T) belonged to the genus Spongiibacterium and showed the highest 16S rRNA gene sequence similarity with Spongiibacterium flavum A11(T) (95.9 %). It showed 16S rRNA gene sequence similarities of 93.2-94.8 % with members of the genera Croceitalea and Flagellimonas in the family Flavobacteriaceae. Optimal growth occurred in the presence of 3-4 % (w/v) NaCl, at pH 8.0 and at 28 °C. The DNA G+C content of strain SW169(T) was 43.3 mol%. The major fatty acids were iso-C15 : 1 G, iso-C15 : 0, iso-C17 : 0 3-OH, iso-C15 : 0 3-OH and summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c,). The major respiratory quinone was menaquinone-6. The major polar lipids were phosphatidylethanolamine, one unidentified aminolipid and one unidentified lipid. On the basis of the polyphasic analyses, strain SW169(T) is considered to represent a novel species of the genus Spongiibacterium, for which the name Spongiibacterium pacificum sp. nov. is proposed. The type strain is SW169(T) ( = JCM 18379(T) = LMG 26997(T)). An emended description of the genus Spongiibacterium is also provided.


Tobacco and the European common agricultural policy.
The common agricultural policy of the European Community subsidizes tobacco production to the tune of 1,300 million ecu a year (US$ 1,500 million, UK pounds 900 million). This amounts to 2,500 ecu ($3,100, pounds 1,700) per minute, and is more in one year than the total amount spent on tobacco subsidies by the US in the last 50 years. The purpose of this policy was to maintain farmers' incomes and adapt community production to demand. Demand for the dark tobaccos which dominate EC production has fallen, while demand for light flue cured tobacco like Virginia has risen. A complex system of production subsidies and quotas was intended to discourage production of the dark tobaccos, for which there is virtually no market, and lead to more Virginia production. The policy has failed. Expenditure has spiralled out of control, production of unmarketable tobacco varieties has risen enormously, and the EC is the world's largest importer of raw tobacco. As a result tobacco is being bought by the community for intervention storage and surpluses of the dark high tar varieties are being 'exported' to eastern Europe and north Africa at giveaway prices. There has been no effective monitoring or control of this policy. This paper explains how this has happened and argues that, in view of the health risks attached to tobacco, these subsidies should be abolished.