Self-reported verbal abuse in 1300+ older women within a private, tertiary women's health clinic.
Several studies describe "elder abuse" among residents of nursing homes, but this issue is less well studied among independently functioning, community-based women. The current study was undertaken to report rates of self-reported intimate partner violence - with a focus on verbal abuse - among older women within a private tertiary women's health clinic. This study focused on women who completed a questionnaire on domestic abuse. A total of 1389 women with a median age of 55 years (range: 50, 90) are the focus of this report. Most 1102 (79%) were married. Within this group, 100 (7%) women reported verbal abuse within the last year. Rates of physical and sexual abuse were much lower with 9 women (1%) and 2 (<1%), respectively. In univariate analyses, being divorced, being an alcoholic, and having suffered prior abuse were associated with reported verbal abuse. In multivariate analyses, self-reported alcoholism and physical abuse were independently associated with reported verbal abuse. This study found a notable rate of patient-reported verbal abuse in older women within a private, tertiary women's health clinic. This observation should prompt healthcare providers to ask about intimate partner violence - and specifically verbal abuse - regardless of healthcare setting.


Severe cefepime-induced status epilepticus treated with haemofiltration.
Neurotoxicity caused by cefepime may occur predominantly in patients with impaired renal function. A case of a cefepime-induced non-convulsive status epilepticus (NCSE) is presented. A 65-year-old woman suffered a severe NCSE due to cefepime in the presence of acute renal failure, requiring coma induction with sodium thiopental. A serious interaction between valproic acid (VPA) and meropenem was also produced after changing cefepime to meropenem. Continuous veno-venous haemofiltration was employed to improve cefepime clearance, and the patient progressively regained her previous mental condition. In conclusion, the cefepime dose must be adjusted according to renal function in order to avoid toxicity in patients with renal failure. Electroencephalogram should be considered in cases of acute confusional state in patients receiving cefepime, to achieve early detection of NCSE. Continuous renal replacement therapy may be successfully employed in severe cases in order to accelerate cefepime removal. Likewise, meropenem should not be used concomitantly with VPA.


An extension of the mixed-effects growth model that considers between-person differences in the within-subject variance and the autocorrelation.
Experience sampling methods have led to a significant increase in the availability of intensive longitudinal data. Typically, this type of data is analyzed with a mixed-effects model that allows to examine hypotheses concerning between-person differences in the mean structure by including multiple random effects per individual (eg, random intercept and random slopes). Here, we describe an extension of this model that-in addition to the random effects for the mean structure-also includes a random effect for the within-subject variance and a random effect for the autocorrelation. After the description of the model, we show how its parameters can be efficiently estimated using a marginal maximum likelihood (ML) approach. We then illustrate the model using a real data example. We also present the results of a small simulation study in which we compare the ML approach with a Bayesian estimation approach.


A Green HPLC Method for Determination of Nine Sulfonamides in Milk and Beef, and Its Greenness Assessment with Analytical Eco-Scale and Greenness Profile.
Sulfonamides have been widely used in the prevention and clinical treatment of bacterial diseases in livestock and poultry. The use of sulfonamides increases the risk of veterinary drug residues in animal derived foods. The traditional reversed phase liquid chromatography methods for sulfonamides residues detection in animal derived foods have the problem of high consumption of organic solvents. The aim of this study was to establish a green high-performance liquid chromatography method for the detection of sulfonamides residues in different animal-origin foods. The sample extraction solutions were purified by the Agela Cleanert PEP-2 cartridge and analyzed by the high-performance liquid chromatography method using ethanol as the green alternative solvent. The proposed method was validated in terms of linear range (20-1000 μg/kg), limit of detection (3.0-12.3 μg/kg), limit of quantitation (10-43 μg/kg), accuracy (80.7-101.3%), and repeatability and reproducibility (RSD <5.9% and RSD <8.5% respectively). The proposed method is an environmentally friendly, sensitive and reliable high-performance liquid chromatography method for simultaneous determination of sulfonamide residues in animal-origin foods. In this work, we firstly developed a green high-performance liquid chromatography method for simultaneous determination of the residues of nine sulfonamides in milk and beef with ethanol as the green alternative solvent.


Light-induced psbA translation in plants is triggered by photosystem II damage via an assembly-linked autoregulatory circuit.
The D1 reaction center protein of photosystem II (PSII) is subject to light-induced damage. Degradation of damaged D1 and its replacement by nascent D1 are at the heart of a PSII repair cycle, without which photosynthesis is inhibited. In mature plant chloroplasts, light stimulates the recruitment of ribosomes specifically to psbA mRNA to provide nascent D1 for PSII repair and also triggers a global increase in translation elongation rate. The light-induced signals that initiate these responses are unclear. We present action spectrum and genetic data indicating that the light-induced recruitment of ribosomes to psbA mRNA is triggered by D1 photodamage, whereas the global stimulation of translation elongation is triggered by photosynthetic electron transport. Furthermore, mutants lacking HCF136, which mediates an early step in D1 assembly, exhibit constitutively high psbA ribosome occupancy in the dark and differ in this way from mutants lacking PSII for other reasons. These results, together with the recent elucidation of a thylakoid membrane complex that functions in PSII assembly, PSII repair, and psbA translation, suggest an autoregulatory mechanism in which the light-induced degradation of D1 relieves repressive interactions between D1 and translational activators in the complex. We suggest that the presence of D1 in this complex coordinates D1 synthesis with the need for nascent D1 during both PSII biogenesis and PSII repair in plant chloroplasts.


A difference infrared spectroscopic study of gramicidin A, alamethicin and bacteriorhodopsin in perdeuterated dimyristoylphosphatidylcholine.
Difference infrared spectroscopy has been used to study the way in which the intrinsic molecules gramicidin A, alamethicin and bacteriorhodopsin perturb their environment when present within a lipid bilayer structure. Dimyristoylphosphatidylcholine containing perdeuterated chains has been used to enable the lipid chain C-2H stretching absorption band to be separated from the C-H bands arising from the intrinsic polypeptide or protein. The C-2H stretching bands of the phospholipid are sensitive to two different types of chain conformation. The C-2H stretching frequency provides information about the static order of the lipid chains, whilst the half-maximum bandwidth provides a measure of chain librational and torsional motion. From the measurements it is concluded that: (1) Above the lipid phase transition temperature tc, low concentrations of either gramicidin A or alamethicin cause a small decrease in lipid chain gauche isomers whilst bacteriorhodopsin in the lipid bilayer has no effect. At higher concentrations each intrinsic molecule causes an increase to occur in lipid chain gauche isomers. (2) The lipid acyl chain motion, as deduced from the bandwidths is increased by the presence of a low concentration of gramicidin A within the lipid bilayer. The presence of the other intrinsic molecules studied have little effect. A higher concentration of alamethicin causes a decrease in chain motion whilst gramicidin A and bacteriorhodopsin have no effect. (3) Below tc each of the intrinsic molecules when present in the lipid bilayer causes an increase in gauche isomers to occur as well as an increase in the lipid chain motion. A broadening of the lipid phase transition occurs as the concentration of the polypeptide increases.


Effects of the interaction of sex and food intake on the relation between energy expenditure and body composition.
The relation between physical activity energy expenditure (PAEE) and percentage body fat (%BF) is not very strong in the general population. It is possible that variables such as sex, food intake, or both may in part explain this poor coupling. This study was designed to show the relation between PAEE and %BF and to determine whether sex, food intake, or both influence the strength of the relation. We used doubly labeled water or energy intake balance, indirect calorimetry, dietary interview, and dual-energy X-ray absorptiometry to measure total energy expenditure (TEE), resting energy expenditure (REE), food intake, and %BF, respectively, in 91 healthy persons (women: aged 48 y, 38.6%BF, n = 47; men: aged 47 y, 24.1%BF, n = 44). TEE, PAEE, and REE were significantly lower in women than in men. TEE was related to %BF in women (r = 0.53, P < 0.0001) but not in men (r = -0.22, P > 0.05). The relation between PAEE and %BF was significant in men (r = -0.34, P < 0.03) but not in women. PAL was also significantly related to %BF in men (r = -0.36, P < 0.02) but not in women. Macronutrient intake (% of total energy) did not differ significantly between the sexes, but carbohydrate (r = -0.44, P < 0.003) and fat (r = 0.31, P < 0.04) intakes were significantly related to %BF in women. These results suggest that the relation between PAEE and %BF is stronger in men than in women. Macronutrient composition seems have a stronger influence on %BF in women than in men.


Effect of pyrolysis temperature and correlation analysis on the yield and physicochemical properties of crop residue biochar.
The aim of this study was to evaluate how pyrolysis temperature influences the yield and physicochemical properties of biochar. We produced biochar from four feedstocks (wheat straw, corn straw, rape straw, and rice straw) pyrolyzed at 300, 400, 500, and 600 °C for 1 h, respectively. The results showed that all biochar yields decreased consistently with increasing temperature during pyrolysis and showed a steady decrease over 400 °C. Rice straw derived biochar had high yield superiority due to its higher content of ash. Pyrolysis temperature has significant effects on the properties of biochar; demonstrating a negative relationship with H, O, H/C, O/C, (O + N)/C, and functional groups, whilst having a positive relationship with C, ash, pH, electrical conductivity, and surface roughness. Higher pyrolysis temperature was beneficial to the formation of a more recalcitrant constitutions and crystal structure, making it available for material application.


Similar efficacy and safety of LY2963016 insulin glargine and insulin glargine (Lantus®) in patients with type 2 diabetes who were insulin-naïve or previously treated with insulin glargine: a randomized, double-blind controlled trial (the ELEMENT 2 study).
To compare the efficacy and safety of LY2963016 insulin glargine (LY IGlar) and the reference product (Lantus(®)) insulin glargine (IGlar) in combination with oral antihyperglycaemic medications in patients with type 2 diabetes (T2D). This phase III, randomized, double-blind, 24-week study enrolled patients with T2D who were insulin-naïve [glycated haemoglobin (HbA1c) ≥7 and ≤11.0%] or previously on IGlar (HbA1c ≤11%) and treated with ≥2 oral antihyperglycaemic medications. Patients were randomized to receive once-daily LY IGlar (n = 376) or IGlar (n = 380) for 24 weeks. The primary efficacy outcome was to test the non-inferiority (0.4% and then 0.3% margin) of LY IGlar to IGlar, as measured by change in HbA1c from baseline to 24 weeks. Both treatment groups had similar and significant (p < 0.001) within-group decreases in mean HbA1c values from baseline. LY IGlar met non-inferiority criteria compared with IGlar for change in HbA1c from baseline [-1.29 vs -1.34%; respectively, least-squares mean difference 0.052% (95% confidence interval -0.070 to 0.175); p > 0.05]. There were no treatment differences (p > 0.05) in fasting plasma glucose, proportion of patients reaching HbA1c <7% or insulin dose at 24 weeks. Adverse events, allergic reactions, weight change, hypoglycaemia and insulin antibodies were similar between treatment groups. Similar findings were observed in patients who were insulin-naïve or previously treated with IGlar at baseline. Both LY IGlar and IGlar, when used in combination with oral antihyperglycaemic medications, provided effective and similar glucose control with similar safety profiles in patients with T2D.


Patient safety indicators for England from hospital administrative data: case-control analysis and comparison with US data.
To assess the feasibility of deriving patient safety indicators for England from routine hospital data and whether they can indicate adverse outcomes for patients. Nine patient safety indicators developed by the United States Agency for Healthcare Research and Quality (AHRQ) were derived using hospital episode statistics for England for 2003-4, 2004-5, and 2005-6. A case-control analysis was undertaken to compare length of stay and mortality between cases (patients experiencing the particular safety event measured by an indicator) and controls matched for age, sex, health resource group (standard groupings of clinically similar treatments that use similar levels of healthcare resource), main specialty, and trust. Comparisons were undertaken with US data. All NHS trusts in England. Inpatients in NHS trusts. There was fair consistency in national rates for the nine indicators across three years. For all but one indicator, hospital stays were longer in cases than in matched controls (range 0.2-17.1 days, P<0.001). Mortality in cases was also higher than in controls (5.7-27.1%, P<0.001), except for the obstetric trauma indicators. Excess length of stay and mortality in cases was greatest for postoperative hip fracture and sepsis. England's rates were lower than US rates for these indicators. Increased length of stay in cases was generally greater in England than in the US. Excess mortality was also higher in England than in the US, except for the obstetric trauma indicators where there were few deaths in both countries. Differences between England and the US in excess length of stay and mortality were most marked for postoperative hip fracture. Hospital administrative data provide a potentially useful low burden, low cost source of information on safety events. Indicators can be derived with English data and show that cases have poorer outcomes than matched controls. These data therefore have potential for monitoring safety events. Further validation, for example, of individual cases, is needed and levels of event recording need to improve. Differences between England and the US might reflect differences in the depth of event coding and in health systems and patterns of healthcare provision.


Cerebral Hyperperfusion Syndrome, an Unusual but Disastrous Complication of Carotid Recanalization: A Case Report.
Cerebral hyperperfusion syndrome (CHS), known as the dark side of carotid recanalization, happens in about 0%-3% of patients. Unfortunately, physicians involving in carotid recanalization generally are not aware of diagnostic and therapeutic aspects of this unusual but potentially life-threatening disorder. Severe bilateral carotid stenosis is suggested to predispose patients to CHS by decrement of cerebrovascular reactivity in a setting of chronic hypoperfusion state. We here introduced such a case; a 69-year-old man, a known case of hypertension and ischemic heart disease, who developed progressive intracranial hypertension underlying CHS after carotid stenting because of symptomatic severe bilateral carotid stenosis.


Effects of bile acids on expression of the human apical sodium dependent bile acid transporter gene.
Using a luciferase reporter assay in both LMH cells and Caco2 cells we found that certain bile acids including unconjugated deoxycholic and others transactivated the ileal apical sodium-dependent bile acid transporter (ASBT) at concentrations ranging from 20 to 300 microM. Confirming this effect, addition of deoxycholic acid to fresh human ileal biopsies caused an approximate 40% increase in endogenous ASBT mRNA production. Promoter deletion analysis indicated the effect of bile acids was mediated by a response element located in the downstream half of the 5'-UTR, a region known to contain a retinoic acid (RXR/RAR) response element and an activated protein-1 (AP-1) response element. Site-directed mutagenesis of the RAR/RXR response element actually enhanced response to deoxycholic acid. Site-directed mutagenesis of the downstream AP-1 response element reduced activation by deoxycholic acid while deletion of this response element completely eliminated this response. The epidermal growth factor (EGF) receptor inhibitor, AG1478, completely eliminated the response to bile acid while the mitogen-activated protein extracellular signal-regulated kinase cascade (MEK) inhibitor, U0126, partially inhibited the response to bile acid. These studies demonstrate that certain bile acids stimulate ASBT gene expression acting on the down-stream AP-1 response element via the EGF receptor and MEK cascade.


Malaria case management by community health workers in the Central African Republic from 2009-2014: overcoming challenges of access and instability due to conflict.
In the Central African Republic (CAR), decades of armed conflict have crippled the public health system. This has left the population without timely access to life-saving services and therefore vulnerable to the numerous consequences of infectious diseases, including malaria. As a response, in 2008 an international non-governmental organization started a network of community health workers (CHWs) in the highly malaria-endemic region of northwest CAR. The area has experienced years of violent clashes between rebel groups and seen hundreds of thousands of people displaced. Data from routine patient registers from 80 CHWs working in Paoua and Markounda sub-prefectures were entered and retrospectively reviewed. The time period covered December 2009-April 2014 and hence different stages of conflict and unrest. Several indicators were measured over time, including malaria rapid diagnostic test (RDT) positivity rates, CHW reporting rates, and malnutrition indicators. Among nearly 200,000 people who consulted a CHW during this period, 81% were found to be positive for malaria parasites by RDT. In total, 98.9% of these positive cases were appropriately treated with artemisinin-based combination therapy (ACT). Only 1.2% of RDT negative cases were incorrectly treated with an ACT. Monthly data from each CHW were regularly reported, with more than 96% of CHWs reporting each month in the first 3 years of the project. However, since the coup d'état in March 2013, the number of CHWs reporting each month decreased as the programme battled the additional constraints of civil war. Although the political crisis affected the CHWs, the programme showed that it could reach those most vulnerable and continue some level of care at all times. In addition, this programme revealed that surveillance could be maintained in conflict zones. This paper fills a significant gap in the knowledge of malaria control in CAR and this is especially important for agencies which must often decide in a short space of time how to respond effectively to complex emergencies.


Neuroanatomical Models of Muscle Strength and Relationship to Ambulatory Function in Spinal Muscular Atrophy.
Individuals with spinal muscular atrophy (SMA) III walk independently, but experience muscle weakness, gait impairments, and fatigue. Although SMA affects proximal more than distal muscles, the characteristic pattern of selective muscle weakness has not been explained. Two theories have been proposed: 1) location of spinal motor neurons; and 2) differences in segmental innervation. To identify neuroanatomical models that explain the selective muscle weakness in individuals with SMA and assess the relationship of these models to ambulatory function. Data from 23 ambulatory SMA participants (78.2% male), ages 10-56 years, enrolled in two clinical studies (NCT01166022, NCT02895789) were included. Strength was assessed using the Medical Research Council (MRC) score; ambulatory function was measured by distance walked on the 6-minute walk test (6 MWT). Three models were identified, and relationships assessed using Pearson correlation coefficients and linear regression. All models demonstrated a positive association between strength and function, (p < 0.02). Linear regression revealed that Model 3B, consisting of muscles innervated by lower lumbar and sacral segments, explained 67% of the variability observed in 6 MWT performance (β= 0.670, p = 0.003). Muscles innervated by lower lumbar and sacral segments, i.e. hip extensors, hip abductors, knee flexors and ankle dorsiflexors, correlated with and predicted greater ambulatory function. The neuroanatomical patterns of muscle weakness may contribute to a better understanding of disease mechanisms and enable delivery of targeted therapies.


Evidence for the paternal mitochondrial DNA in the crucian carp-like fish lineage with hybrid origin.
In terms of taxonomic status, common carp (Cyprinus carpio, Cyprininae) and crucian carp (Carassius auratus, Cyprininae) are different species; however, in this study, a newborn homodiploid crucian carp-like fish (2n=100) (2nNCRC) lineage (F1-F3) was established from the interspecific hybridization of female common carp (2n=100)×male blunt snout bream (Megalobrama amblycephala, Cultrinae, 2n=48). The phenotypes and genotypes of 2nNCRC differed from those of its parents but were closely related to those of the existing diploid crucian carp. We further sequenced the whole mitochondrial (mt) genomes of the 2nNCRC lineage from F1 to F3. The paternal mtDNA fragments were stably embedded in the mt-genomes of F1-F3 generations of 2nNCRC to form chimeric DNA fragments. Along with this chimeric process, numerous base sites of F1-F3 generations of 2nNCRC underwent mutations. Most of these mutation sites were consistent with the existing diploid crucian carp. Moreover, the mtDNA organization and nucleotide composition of 2nNCRC were more similar to those of the existing diploid crucian carp than those of the parents. The inheritable chimeric DNA fragments and mutant loci in the mt-genomes of different generations of 2nNCRC provided important evidence of the mtDNA change process in the newborn lineage derived from hybridization of different species. Our findings demonstrated for the first time that the paternal mtDNA were transmitted into the mt-genomes of homodiploid lineage, which provided new insights into the existence of paternal mtDNA in the mtDNA inheritance.


Treatment of natural Protostrongylus rufescens lungworm infection in sheep with eprinomectin 5 mg/mL topical solution.
Parasitic respiratory infections in domestic sheep and goats are caused by Dictyocaulus filaria and various species belonging to the Protostrongylidae family of nematodes which frequently occur in mixed infections. Although the parasitism with protostrongylid lungworms is generally considered to be of low pathogenicity, there are reports of clinical disease including cases associated with Protostrongylus rufescens infection. The efficacy against P. rufescens of eprinomectin 5 mg/mL topical solution (EPRINEX® Multi, Boehringer Ingelheim) was thus evaluated in a clinical study compliant with GCP and VICH anthelmintic efficacy testing guidelines in adult sheep with naturally acquired infection. Following ranking on pre-treatment Protostrongylus fecal larval counts and forming into blocks of two animals, the sheep were randomly allocated to either remain untreated (control) or to be administered eprinomectin 5 mg/mL topical solution at 1 mL/5 kg body weight (equivalent to 1 mg eprinomectin per kg body weight) once as a pour-on. Fecal samples of the sheep were examined to monitor the larval excretion weekly for five weeks after treatment; then the animals were necropsied for lungworm recovery and count to determine the efficacy of the treatment. After treatment, Protostrongylus larval excretion decreased to zero within three weeks. Nematode counts demonstrated that the efficacy of the treatment with eprinomectin 5 mg/mL topical solution was 100 % against P. rufescens: no lungworms were recovered from any treated sheep while all controls harbored P. rufescens (range, 17-406) (p < 0.001). The treatment was well accepted; no treatment-related health problems were observed.


Regional distribution of bombesin and seven other regulatory peptides in the human brain.
In order to compare within the same brains the quantitative distributions of a range of neuropeptides, bombesin, N- and C-terminal glucagon, cholecystokinin, neurotensin, somatostatin, substance P and vasoactive intestinal polypeptide immunoreactivities were determined by radioimmunoassay in 24 regions of 5 normal adult human brains. Each peptide showed a different distribution pattern. Of the peptides not previously mapped in detail in the human brain, bombesin-like immunoreactivity was present in all regions with the highest concentrations in particular areas of the hypothalamus, septal nuclei, nucleus accumbens, globus pallidus, amygdala, periaqueductal grey and substantia nigra. C- and N-terminal glucagon immunoreactivities were detected only in the ventromedial hypothalamus. The concentrations of the remaining 5 peptide immunoreactivities, and their molecular forms, were in good general agreement with those reported individually by others in both human brains and those of experimental animals. The quantitative mapping of the regulatory peptides in the human brain provides an essential base for further comparative study in diseased postmortem brains.


Synthesis and biological evaluation of phosphorylated flavonoids as potent and selective inhibitors of cholesterol esterase.
A series of phosphorylated flavonoids were synthesized and investigated in vitro as inhibitors of pancreatic cholesterol esterase (CEase) and acetylcholinesterase (AChE). The results showed that most of the synthesized compounds exhibited nanomolar potency against CEase, much better than the parent flavonoids. Furthermore, these phosphorylated flavonoids demonstrated good to high selectivity for CEase over AChE, which only showed micromolar potency inhibition of AChE. The most selective and potent inhibitor of CEase (3e) had IC₅₀ value of 0.72 nM and 11800-fold selectivity for CEase over AChE. The structure-activity relationships revealed that the free hydroxyl group at position 5 and phosphate group at position 7 of the phosphorylated flavonoids are favorable to the inhibition of CEase. The inhibition mechanism and kinetic characterization studies indicated that they are irreversible competitive inhibitors of CEase.


A site-directed mutagenesis analysis of tNOX functional domains.
Constitutive NADH oxidase proteins of the mammalian cell surface exhibit two different activities, oxidation of hydroquinones (or NADH) and protein disulfide-thiol interchange which alternate to yield oscillatory patterns with period lengths of 24 min. A drug-responsive tNOX (tumor-associated NADH oxidase) has a period length of about 22 min. The tNOX cDNA has been cloned and expressed. These two proteins are representative of cycling oxidase proteins of the plant and animal cell surface. In this report, we describe a series of eight amino acid replacements in tNOX which, when expressed in Escherichia coli, were analyzed for enzymatic activity, drug response and period length. Replacement sites selected include six cysteines that lie within the processed plasma membrane (34 kDa) form of the protein, and amino acids located in putative drug and adenine nucleotide (NADH) binding domains. The latter, plus two of the cysteine replacements, resulted in a loss of enzymatic activity. The recombinant tNOX with the modified drug binding site retained activity but the activity was no longer drug-responsive. The four remaining cysteine replacements were of interest in that both activity and drug response were retained but the period length for both NADH oxidation and protein disulfide-thiol interchange was increased from 22 min to 36 or 42 min. The findings confirm the correctness of the drug and adenine nucleotide binding motifs within the tNOX protein and imply a potential critical role of cysteine residues in determining the period length.


Mathematical tools for planning effective intervention scenarios for sexually transmitted diseases.
We studied the dynamics of sexually transmitted diseases in structured populations, deriving analogies from the theory of metapopulations. The goal was to study the impact of potential interventions, such as reducing the probability of transmission (e.g., by condom use), reducing the duration of infectiousness (e.g., by early diagnosis and treatment), or reducing the number of new contacts. A structured SIS model was used for the study. We extended the concept of core groups to the concept of nodal epidemiologic contribution (NEC) by considering the contribution that an individual in a particular (social, spatial, or other such) group makes to a target quantity, such as the threshold condition for disease persistence, the equilibrium prevalence, or the number of disease transmissions in the long term. The measures for NEC derived here are analogous to patch values in metapopulation theory, which measure the contributions of particular habitat patches to various-aspects of metapopulation dynamics. Our results highlight that intervention measures should be targeted especially promptly if the goal is the complete eradication of the disease, as the variance in the contributions made by the individuals is the highest for this case.


[The role of adrenergic receptors in the realization of hypothalamic effects on the motor function of the digestive tract in hypophysectomized dogs].
Chronic experiments on hypophysectomized dogs with gastric and small intestinal fistulas as well as with hypothalamus-implanted electrodes have shown that blockade of alfa-adrenoreceptors by phentolamine increases the number of the excitatory motility responses while stimulating hypothalamic structures during rest of the gastrointestinal tract and decreases inhibitory effects of the stomach while stimulating hypothalamic structures during work of the digestive tract. The blockade of beta-adrenoreceptors by obsidan induces weakening of excitatory responses of the digestive tract and intensification of inhibitory ones while stimulating hypothalamic structures in hypophysectomized dogs.


Relative deprivation, social exclusion, and quality of life among Chinese internal migrants.
Factors contributing to diminishing quality of life (QOL) of migrants have been examined, but little is known about the impact of relative deprivation. This study aimed to clarify the effects of relative deprivation on QOL and mediating effects of social exclusion among Chinese internal migrants. This is a secondary data analysis of a nationally representative survey. We obtained data from 14,816 internal immigrants, aged 15-59 years, throughout China using the 2014 China Migrants Dynamic Survey (CMDS). We measured relative deprivation via a modified Yitzhaki Index, social exclusion using a four-point Likert scale, and QOL using the Kessler Psychological Distress Short Scale, the Satisfaction with Life Scale, and a subscale of the 36-item Short-Form Health Survey. Survey data of 15,996 local residents were also retrieved and analyzed to make possible comparisons between the local and migrant population. Furthermore, we used descriptive and statistical analyses with data from the CMDS to identify relative deprivation and social exclusion. The results show relative deprivation both directly and indirectly influences Chinese internal migrants' QOL. Specifically, compared with the local population, relative deprivation triggers serious social exclusion (β = 0.008, P < 0.001), ultimately deteriorating QOL. Social exclusion partially mediated the total effects of relative deprivation on mental illness (β = 0.004, P < 0.001), self-rated health (β = -0.285, P < 0.001), and life satisfaction (β = -0.020, P < 0.001) among Chinese internal migrants. Relative deprivation significantly impacts QOL by exacerbating mental illness, eroding self-rated health, and inhibiting life satisfaction. Relative deprivation is significantly directly associated with various indicators of QOL and indirectly affects QOL through social exclusion. In addition, our results demonstrate that the relative deprivation theoretical approach and the modified Yitzhaki Index are worthy of future investigation in studies of migrants' health.


Accurate Model-Based Point of Gaze Estimation on Mobile Devices.
The most accurate remote Point of Gaze (PoG) estimation methods that allow free head movements use infrared light sources and cameras together with gaze estimation models. Current gaze estimation models were developed for desktop eye-tracking systems and assume that the relative roll between the system and the subjects' eyes (the 'R-Roll') is roughly constant during use. This assumption is not true for hand-held mobile-device-based eye-tracking systems. We present an analysis that shows the accuracy of estimating the PoG on screens of hand-held mobile devices depends on the magnitude of the R-Roll angle and the angular offset between the visual and optical axes of the individual viewer. We also describe a new method to determine the PoG which compensates for the effects of R-Roll on the accuracy of the POG. Experimental results on a prototype infrared smartphone show that for an R-Roll angle of 90 ° , the new method achieves accuracy of approximately 1 ° , while a gaze estimation method that assumes that the R-Roll angle remains constant achieves an accuracy of 3.5 ° . The manner in which the experimental PoG estimation errors increase with the increase in the R-Roll angle was consistent with the analysis. The method presented in this paper can improve significantly the performance of eye-tracking systems on hand-held mobile-devices.


Fleas and Flea-Associated Bartonella Species in Dogs and Cats from Peru.
In the present study, we investigated 238 fleas collected from cats and dogs in three regions of Peru (Ancash, Cajamarca, and Lima) for the presence of Bartonella DNA. Bartonella spp. were detected by amplification of the citrate synthase gene (16.4%) and the 16S-23S intergenic spacer region (20.6%). Bartonella rochalimae was the most common species detected followed by Bartonella clarridgeiae and Bartonella henselae. Our results demonstrate that dogs and cats in Peru are infested with fleas harboring zoonotic Bartonella spp. and these infected fleas could pose a disease risk for humans.


Chronic Hepatitis B Virus and Hepatitis D Virus: New Developments.
Hepatitis B virus (HBV) and hepatitis D virus are leading causes of morbidity and mortality worldwide. Despite the availability of HBV vaccinations that are 98% to 100% effective, an estimated 820,000 annual deaths were attributed to HBV in 2019, mainly related to the sequelae of cirrhosis and hepatocellular carcinoma. Because disease prevalence is concentrated outside of the United States, it is overlooked, but with expanded vaccination recommendations provided by the Centers for Disease Control and Prevention and recommended screening, as well as heightened awareness by health care providers, we can work toward the eradication of this preventable disease.


Crystallization of human gelsolin.
Human gelsolin has been crystallized by microdialysis techniques to give single crystals that diffract to 3.5 A resolution. The crystals belong to space group P42(1)2 and have cell dimensions a = 175.0 A, c = 151.6 A. They contain two gelsolin molecules in the asymmetric unit.


[Effect of intravascular laser irradiation of the blood on blood cells in pancreatitis].
Inpatient examinations included 17 patients with necrosis of the pancreas (4 patients had hemorrhagic and 14 fat necrosis): synthetic lymphocyte activity was studied by the luminescent method and the erythrocyte content of adenyl nucleotides by thin-layer chromatography in the toxic phase of pancreatitis. Synthetic lymphocyte activity was found to be decreased and the ATP pool of erythrocytes exhausted in the toxic phase of pancreatitis. Intravascular laser irradiation of the blood caused recovery of lymphocyte activity and increase in the ATP content in erythrocytes.


DUNBID, the Delft University neutron backscattering imaging detector.
In the search for low-metallic land mines, the neutron backscattering technique may be applied if the soil is sufficiently dry. An advantage of this method is the speed of detection: the scanning speed may be made comparable to that of a metal detector. A two-dimensional position sensitive detector is tested to obtain an image of the back scattered thermal neutron radiation. Results of experiments using a radionuclide neutron source are presented. The on-mine to no-mine signal ratio can be improved by the application of a window on the neutron time-of-flight. Results using a pulsed neutron generator are also presented.


Absence of planned neck dissection for the N2-N3 neck after chemoradiation for locally advanced squamous cell carcinoma of the head and neck.
To review our institutional experience of patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) and N2-N3 neck disease with respect to neck recurrence after chemoradiation without planned neck dissection (ND). Retrospective study. Tom Baker Cancer Centre, Calgary, Alberta, Canada. Fifty-four adults with locally advanced SCCHN and N2-N3 neck disease. Eighty consecutive patients were treated with chemoradiation, 70 Gy given as 2 Gy daily for 7 weeks, with cisplatin, 20 mg/m(2), given on the first 4 days of weeks 1 and 5. Of the 80 patients, 54 were evaluable. Primary outcomes were overall survival and absence or presence of neck disease after chemoradiation. Secondary outcomes included disease-specific survival and locoregional recurrence-free survival. Median follow-up of living patients was 35 months. Patients with a complete response (CR) did not have any planned ND. Factors associated with the absence of recurrent neck disease included CR (P < .001), younger age (P = .02), and better Karnofsky Performance Status (P = .049). In patients achieving CR, 2-year overall, disease-specific, and locoregional recurrence-free survival was 92%, 95%, and 95%, respectively. Three of the 43 patients (7%) with N2 lesions obtaining CR subsequently experienced a neck recurrence at a median of 15 months (range, 7-24 months). In these patients with locally advanced SCCHN and N2-N3 neck disease treated with chemoradiation and achieving CR, only a few patients with N2 neck disease experienced recurrence despite the absence of planned ND. Prospective trials are needed to identify patients with N2 neck disease who may still benefit from planned ND after chemoradiation. There were not enough patients with N3 neck disease to make any recommendations.


Functional analysis of a complex oncogene arrangement in biotype III Agrobacterium tumefaciens strains.
The ubiquitous grapevine-associated octopine/cucumopine Ti plasmids of biotype III Agrobacterium tumefaciens strains carry two T regions, TA and TB, with a complex oncogene arrangement. Within the octopine/cucumopine group, two main strain types were identified: 'large TA' strains with a TA region resembling the TL region of the biotype I octopine strain Ach5 and 'small TA' strains with a similar T region organization as the 'large TA' strains but with a large internal TA deletion. Structural and functional studies of the representative 'large TA' strain Tm4 revealed six oncogenes. Each oncogene was inserted in a disarmed vector and tested for biological activity using the corresponding oncogenes of Ach5 as standards. Five Tm4 oncogenes, TA-iaaM, T-ipt, T-6b, TB-iaaH and TB-iaaM, were shown to be active, the IS-interrupted TA-iaaH gene was inactive. To study the role of each gene in the pTiTm4 context, several single and multiple pTiTm4 mutations were constructed. It was shown that whereas TA-iaaM and TB-iaaH are essential for tumour formation on grapevine, T-ipt, T-6b and TB-iaaM are not. The avirulence of the TA-iaaM- mutant was shown to be due to an inhibitory effect of the T-ipt gene, since a TA-iaaM-/T-ipt- double mutant was fully virulent. We conclude that the TA-iaaM gene of 'large TA' strains is specifically required to counteract the tumour growth inhibiting activity of the T-ipt gene. Both TA-iaaM and T-ipt are absent from the 'small TA' strains. A model on the roles and interactions of the different oncogenes in 'large TA' and 'small TA' strains is presented.


Suppression of reflex tachycardia following alpha-adrenoceptor blockade in conscious dogs: comparison of urapidil with prazosin.
The effects of the alpha-adrenoceptor antagonists urapidil and prazosin were compared as to their ability to suppress or enhance baroreceptor-induced reflex changes in heart rate in conscious dogs. Bradykinin was injected as an intravenous bolus to elicit a vasodepressor response and reflex tachycardia, and angiotensin II was utilized to produce opposite effects via baroreceptor activation. Urapidil, which is an alpha 1- and alpha 2-antagonist, was infused intravenously at 2 and 5 mg/kg, and suppressed reflex tachycardia elicited by bradykinin at both dose levels. The suppression of reflex tachycardia elicited by bradykinin was not evident with intravenous prazosin (0.25 and 0.625 mg/kg), an alpha 1-antagonist. Reflex bradycardia elicited by angiotensin was not affected by urapidil but was enhanced by prazosin. Therefore, urapidil may have a selective effect in suppressing cardiac sympathetic reflexes with no apparent effect on vagal reflexes. Both urapidil and prazosin produced similar decreases in arterial blood pressure with no long-term effects on heart rate, and the degree of alpha-receptor postjunctional blockade by both agents was judged to be equivalent, as determined by intravenous phenylephrine injection. The suppression of reflex tachycardia by urapidil could be eliminated by guanethidine pretreatment, indicating that a cardiosympathoinhibitory effect by urapidil was involved.


Modulation of diet-induced mechanical allodynia by metabolic parameters and inflammation.
Dietary-associated diseases have increased tremendously in our current population, yet key molecular changes associated with high-fat diets that cause clinical pre-diabetes, obesity, hyperglycemia, and peripheral neuropathy remain unclear. This study examines molecular and metabolic aspects altered by voluntary exercise and a high-fat diet in the mouse dorsal root ganglion. Mice were examined for changes in mRNA and proteins encoding anti-inflammatory mediators, metabolic-associated molecules, and pain-associated ion channels. Proteins involved in the synaptosomal complex and pain-associated TRP ion channels decrease in the dorsal root ganglion of high-fat exercise animals relative to their sedentary controls. Exercise reversed high-fat diet induced mechanical allodynia without affecting weight gain, elevated blood glucose, and utilization of fat as a fuel source. Independent of weight or fat mass changes, high-fat exercised mice display reduced inflammation-associated mRNAs. The benefits of exercise on abnormal peripheral nerve function appear to occur independent of systemic metabolic changes, suggesting that the utilization of fats and inflammation in the peripheral nervous system may be key for diet-induced peripheral nerve dysfunction and the response to exercise.


Spatial distribution and migration of 239+240Pu in Chinese soils.
The migration of radionuclides is a critical threat to the soil and groundwater environment. This study investigates highly radiological toxic 239+240Pu in 647 surface soils and 66 soil cores in China. First, the spatial distributions of 239+240Pu activities and 240Pu/239Pu ratios are presented in Chinese surface soils. Second, four different types of vertical distribution of 239+240Pu, namely 45.4%, 40.9%, 9.1% and 4.5% of Chinese soil cores proportions are integrated using statistical analysis. Furthermore, different soil types are accompanied by different 239+240Pu vertical distributions, which relate closely to the 239+240Pu migration. Finally, based on the Convection Dispersion Equation (CDE) model, the present work find that the apparent convection velocities of 239+240Pu are ranging from 0.00032 ± 0.00031 cm a-1 to 0.473 ± 0.083 cm a-1. As shown by the four typical vertical activity distribution of 239+240Pu in soil cores, the deepened activity maximum value position of 239+240Pu implies a fast migration rate or apparent convection velocity. This study, for the first time, suggests a significant linear correlation (R2 = 0.847) between the depth of 239+240Pu maximum value (cm) and the apparent convection velocity (v, cm a-1). We hypothesize that v usually does not exceed 0.5 cm a-1 in the CDE model. A significant linear correlation is also identified between apparent dispersion coefficient (D, cm2 a-1) and v2 in Chinese soil cores from the CDE model. It will provide an important reference for harmful heavy metal migration research in the future.


Determination of the coordination environment of Cu(II) in human hair and its possible relevance to health and hair care treatments.
This paper addresses the question of the coordination environment of copper (II) in hair. The research is based on electron paramagnetic resonance (EPR), a spectroscopic technique that detects specifically paramagnetic molecules. Samples were investigated from various male and female subjects of different ages and races. The Cu(II) EPR signals seemed to be a combination of two components in widely differing relative proportions, although both have the relationship g(// )> g(⊥) > 2.0 expected for the unpaired electron in a d(x2-y2) orbital and are thus consistent with square planar or tetragonal symmetry for the Cu(II) ion. With a very few samples, the EPR spectra consisted of a single component, and high quality spectra from these samples are presented for use as standard reference results. In one type of complex, (14) N superhyperfine structure (shfs) was resolved and the spectrum corresponds to Cu coordination to mixed O- and N-containing functional groups, although the number of N atoms cannot be determined with certainty. No (14) N shfs was seen in the spectrum from the other type of complex, and its narrow linewidth excluded the possibility of any. Furthermore, the spectral parameters are inconsistent with coordination of the Cu to four O atoms, but consistent with some S coordinated to the Cu. Large variations between the relative proportions of the two Cu(II) forms were observed with a single healthy subject over a 5-year period, thus suggesting that they are determined by 'environmental' factors, possibly hair treatment processes, rather than being markers for the health of the subject. EPR spectroscopy is a convenient non-destructive method for determining the Cu coordination environment in hair, and could be used to monitor its response to various types of hair treatment.


Partial desensitization of MYC2 transcription factor alters the interaction with jasmonate signaling components and affects specialized metabolism.
The activity of bHLH transcription factor MYC2, a key regulator in jasmonate signaling and plant specialized metabolism, is sensitive to repression by JASMONATE-ZIM-domain (JAZ) proteins and co-activation by the mediator subunit MED25. The substitution of a conserved aspartic acid (D) to asparagine (N) in the JAZ-interacting domain (JID) of Arabidopsis MYC2 affects interaction with JAZ, although the mechanism remained unclear. The effects of the conserved residue MYC2D128 on interaction with MED25 have not been investigated. Using tobacco as a model, we generated all possible substitutions of aspartic acid 128 (D128) in NtMYC2a. NtMYC2aD128N partially desensitized the repression by JAZ proteins, while strongly interacting with MED25, resulting in increased expression of nicotine pathway genes and nicotine accumulation in tobacco hairy roots overexpressing NtMYC2aD128N compared to those overexpressing NtMYC2a. The proline substitution, NtMYC2aD128P, negatively affected transactivation and abolished the interaction with JAZ proteins and MED25. Structural modeling and simulation suggest that the overall stability of the JID binding pocket is a predominant cause for the observed effects of substitutions at D128. The D128N substitution has an overall stabilizing effect on the binding pocket, which is destabilized by D128P. Our study offers an innovative tool to increase the production of plant natural products.


Predictors of future depression in early and late adolescence.
This study examined whether the possibility to predict future DSM-IV depressive disorder can be increased with recurrent screening for depression in community adolescents, compared to single screening in early or in late adolescence. In addition, it examined which depressive symptoms in early and late adolescence predicted future depressive disorder most accurately. Participants from an ongoing longitudinal cohort study were assessed when they were aged between 10 and 15 (early adolescence), and between 14 and 19 (late adolescence), and were followed until they were 20-25 (young adulthood). The Child Behavior Checklist (CBCL) and Youth Self-Report (YSR) were used to screen for depression in early and late adolescence, and CIDI/DSM-IV diagnoses of depressive disorder were used as the outcome measure during follow-up. Recurrent screening only slightly improved the prediction of future depression, and cognitive and physical symptoms in late adolescence predicted future depression accurately in boys. Sleeping problems in early adolescence predicted future depression in girls. The main limitation was the retrospective recall of the age of onset of a depressive disorder. Recurrent screening for depression did not predict future depressive disorder better than single screening in late adolescence. However, depressive symptoms like sleeping problems predicted future depression quite accurately in adolescent boys and girls. This indicates that it may be useful to screen adolescents for the presence of such symptoms, for instance in school settings, to predict which adolescents are at risk to develop DSM-IV depressive disorder in early adulthood.


Chest physiotherapy during anesthesia for children with cystic fibrosis: effects on respiratory function.
Physiotherapists sometimes use elective surgical procedures for children with cystic fibrosis as an opportunity to perform physiotherapy treatments during anesthesia. These treatments theoretically facilitate direct endotracheal airway clearance and compensate for any post-operative respiratory deterioration related to the anaesthetic and surgery. MATERIALS, PATIENTS, AND METHODS: Children were randomized either to receive physiotherapy or not following anesthesia and intubation. Respiratory mechanics (C(rs) and R(rs)), tidal volume, and peak inspiratory pressure (PIP) were measured immediately before and after physiotherapy. FEV(1) was measured before and after surgery and post-operative physiotherapy requirements were recorded. Eighteen patients, mean age 12 years (range 2.8-15 years) were recruited, with nine in each group. Both groups showed a non-significant decline in FEV(1) the day after surgery compared with pre-operative values (-5.8%: physiotherapy and -7.1%: control). Both PIP and R(rs) increased significantly following physiotherapy (within- and between-groups, P < 0.05). In addition, there was a significant within-group reduction in C(rs) after physiotherapy which approached significance between-groups (P = 0.07). There were no significant within- or between-group differences in tidal volume following treatment in either group. The unanticipated decline in respiratory function immediately following physiotherapy was short-lived and not discernible in longer term outcomes measured by FEV(1) or physiotherapy requirements post-operatively. If respiratory physiotherapy under anesthesia is considered necessary and the benefits of removing secretions are deemed to outweigh the short-term risks, it may be necessary for the anaesthetist to consider modifying ventilatory support to counteract any short-term negative effects of the treatment.


Collective photothermal bending of flexible organic crystals modified with MXene-polymer multilayers as optical waveguide arrays.
The performance of any engineering material is naturally limited by its structure, and while each material suffers from one or multiple shortcomings when considered for a particular application, these can be potentially circumvented by hybridization with other materials. By combining organic crystals with MXenes as thermal absorbers and charged polymers as adhesive counter-ionic components, we propose a simple access to flexible hybrid organic crystal materials that have the ability to mechanically respond to infrared light. The ensuing hybrid organic crystals are durable, respond fast, and can be cycled between straight and deformed state repeatedly without fatigue. The point of flexure and the curvature of the crystals can be precisely controlled by modulating the position, duration, and power of thermal excitation, and this control can be extended from individual hybrid crystals to motion of ordered two-dimensional arrays of such crystals. We also demonstrate that excitation can be achieved over very long distances (>3 m). The ability to control the shape with infrared light adds to the versatility in the anticipated applications of organic crystals, most immediately in their application as thermally controllable flexible optical waveguides for signal transmission in flexible organic electronics.


Standardization of extract mixture of Chaenomeles sinensis and Phyllostachys bambusoides for anti-obesity by HPLC-UV.
JM-101 is a developed functional food formula using water extract of Chaenomeles sinensis and Phyllostachys bambusoides for anti-obesity. Standardization and quality control of herb mixture is more difficult than those of single herb. Additionally, the estimation of mixing ratio is an essential requirement for standardization. This study aimed to develop an efficient analytical method for the standardization of JM-101 based on C. sinensis and P. bambusoides. Protocatechuic acid and p-coumaric acid were selected as marker compounds of JM-101. A mixture of the two medicinal materials (1:1 w/w) was extracted by water and then liquid-liquid extracted (LLE) by ethyl acetate. The supernatant was evaporated to dryness and dissolved in methanol for analysis. The extraction time, material-to-water ratio and ethyl acetate-to-water ratio were optimized by multi-response optimization based on response surface methodology (RSM). The established methods were validated in terms of linearity, precision, accuracy, repeatability, stability and recovery. The novel method based on LLE and RSM provides a sensitive, accurate analysis and excellent extraction efficiency of marker compounds in JM-101, without interruption of other compounds in JM-101. In conclusion, the developed simultaneous analytical method contributes to the standardization of two materials (C. sinensis and P. bambusoides) and JM-101.


Study of energy expenditure during activities of daily living using and not using body position recommended by energy conservation techniques in patients with COPD.
To assess the energy spent by COPD patients using or not using energy conservation techniques (ECTs) during activities of daily living (ADL). The patients were evaluated in two different situations as stated above. For both applications, the following variables were measured during four ADL with or without using postures recommended by ECTs: metabolic (oxygen consumption [V(O2)] and carbon dioxide production [V(CO2)]), ventilatory (minute ventilation), cardiovascular (heart rate [HR] and oxygen pulse), and dyspnea (Borg score). Sixteen male COPD patients (mean age, 62 years) with moderate-to-very-severe COPD (mean FEV1, 40%) participated in the study. The use of ECTs during ADL related to personal hygiene reduced V(O2) (13.4%), V(CO2) (12.8%), HR (13.7%), and Borg score (1 point) [p < 0.05]. Putting on and taking off shoes did not change V(O2), V(CO2), and HR but reduced the Borg score (0.6 point) [p < 0.05]. Storing groceries on high shelves reduced V(O2) (12.2%), V(CO2) (9.9%), HR (5.1%), and Borg score (0.75 point). Storing groceries on low shelves reduced V(O2) (28.1%), V(CO2) (24.3%), HR (5.4%), and Borg score (0.8 point) [p < 0.05]. The use of energy conservation techniques in COPD patients during ADL reduces energy cost and dyspnea perception.


Postoperative Reduction Quality May Be the Most Important Factor That Causes Worse Functional Outcomes in Open and Closed Pelvic Fractures.
Data on the functional outcomes of patients with open pelvic fractures after osteosynthesis are limited, and whether open fracture is a risk factor for worse outcomes, as compared with closed fracture, remains unclear. This study aimed to compare the functional outcomes of patients with open and closed pelvic fractures and evaluate potential factors that might affect outcomes. Overall, 19 consecutive patients with open pelvic fractures and 78 patients with closed pelvic fractures between January 2014 and June 2018 were retrospectively reviewed. All fractures were surgically treated, with a minimal follow-up period of three years. Patients' demographic profile, associated injuries, management protocol, quality of reduction, and outcomes were recorded and analyzed. Patients with open pelvic fractures had higher new injury severity score, higher incidence of diverting colostomy, and longer length of stay. Both radiological and functional evaluations revealed no significant differences between the two groups at 1-year and 3-year evaluations. Multiple logistic regression analysis identified poor radiological outcomes (using Lefaivre criteria) and longer length of stay as risk factors for worse short-term functional outcomes. At 3-year evaluation, fair-to-poor radiological outcomes (using Matta/Tornetta and Lefaivre criteria) and the presence of diverting colostomy were potential risk factors. Compared with closed pelvic fracture, open pelvic fracture was not an indicator of worse functional outcomes. Functional outcomes may be comparable between patients with open and closed pelvic fractures at different time points within three years postoperatively. Achieving anatomical reduction in a fracture is crucial, because it might affect patient satisfaction.


Resveratrol Improves Intestinal Morphology and Anti-Oxidation Ability in Deoxynivalenol-Challenged Piglets.
This study aimed to investigate the potential effects of resveratrol (RES) on intestinal function and oxidative stress in deoxynivalenol (DON)-challenged piglets. Twenty-four healthy Duroc × Yorkshire × Landrace weaned piglets at the age of 28 ± 1 days were randomly divided into four groups with six repetitions per group. The four groups were as follows: the control group (CON), fed with a basic diet; the RES group, fed with a basal diet + 300 mg/kg RES; the DON group, fed with a basal diet containing 2.65 mg/kg DON; and the DON + RES group, fed with a basal diet containing 2.65 mg/kg DON + 300 mg/kg RES. The results showed that the growth performance and intestinal function of DON-challenged piglets were significantly decreased (p < 0.05). Compared with the DON group, the average daily feed intake of piglets in the DON + RES group was significantly increased (p < 0.05). Additionally, dietary RES ameliorated DON-induced intestinal morphology impairment, as indicated by the increased (p < 0.05) jejunal villi height and the ratio of the jejunal villi height/crypt depth. Furthermore, after the addition of RES, the activities of superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) in the jejunum mucosa were significantly increased, and the content of malondialdehyde (MDA) was significantly declined (p < 0.05). In addition, the level of reactive oxygen species (ROS) in the mitochondria was significantly reduced by RES, while the mitochondrial membrane potential in jejunum was significantly increased by RES (p < 0.05). However, there was no obvious difference between DON + RES and DON groups on average daily gain and the ratio of feed togain, except for the significant inhibition of average daily feed intake (p < 0.05). In conclusion, RES could effectively alleviate the DON-induced oxidative stress on weaned piglets, and reduce the damage to mitochondria and intestinal morphology, so as to improve the growth performance of piglets.


Bone marrow infection with bacillus Calmette-Guérin (BCG) after intravesical immunotherapy.
Instillation of bacillus Calmette-Guérin (BCG) into the urine bladder is an effective treatment of superficial bladder cancer. BCG-mediated anti-tumor activity appears to be a local phenomenon in which cell-mediated immunity, involving cytotoxic T cells, lymphokine-activated killer cells and natural killer cells, is important for the elimination of malignant cells. Serious side-effects of BCG therapy are rare; nevertheless, BCG is a live, attenuated strain of Mycobacterium (M.) bovis and may exhibit invasive properties. Both local and distant or generalized infections have been reported after treatment with BCG. We describe the case of a 68-year-old man who developed bone marrow infection with BCG two years after intravesical instillation of BCG for treatment of superficial bladder cancer. He presented with intermittent fever, weight loss and pronounced pancytopenia. A bone marrow biopsy specimen showed granulomatous inflammation and BCG was cultured from the urine. Anti-mycobacterial treatment with isoniazid, rifampicin and ethambutol (pyrazinamide is inactive against M. bovis) led to full clinical recovery of the patient.


The genetic polymorphism down-regulating HLA-DRB1 enhancer activity facilitates HBV persistence, evolution and hepatocarcinogenesis in the Chinese Han population.
Genetic predisposition of human leucocyte antigen (HLA)-DR has been linked to nonresponse to hepatitis B virus (HBV) vaccination. We sought to reveal their effects on chronic infection and evolution of HBV and development of hepatocellular carcinoma (HCC). Genetic polymorphisms at HLA-DR enhancer regions were genotyped in 4588 participants using quantitative PCR. HBV mutations were determined by sequencing. A dual-luciferase assay was applied to detect the enhancer activity. Associations between HLA-DR polymorphisms and postoperative prognosis were investigated in another cohort of 397 HBV-infected HCC patients. Variant alleles (rs3135395-T, rs3135338-C and rs477515-T) were significantly associated with a decreased risk of HBV persistence in Chinese patients. rs3135395-T, rs3135338-C, rs477515-T and rs2395178-G also significantly decreased HCC risk. rs3135395-T, rs477515-T and rs2395178-G were inversely associated with the generation of A1762T/G1764A, T1753V and C1653T, the HCC-risk HBV mutations. Multiplicative interactions of the variant genotypes with the HCC-risk HBV mutations were significantly associated with a decreased risk of HCC. In multivariate Cox analysis, rs477515-T independently predicted a favourable prognosis, with a hazard ratio of 0.48 (P = .002). The activity of the HLA-DRB1 enhancer with rs477515-T was significantly higher than that with rs477515-C. The activity of the HLA-DRB1 enhancer with rs477515-T and that with rs477515-C was significantly up-regulated by interferon-γ and interleukin-4, respectively. Interleukin-6 significantly inhibited the HLA-DRB1 enhancer activity, and this effect was more evident in those carrying rs477515-T. Polymorphisms predisposing to down-regulation of HLA-DR facilitate the Th1-to-Th2 transition and promote HCC development, possibly via selecting the HCC-risk HBV mutations. This can be transformed into specific prophylaxis of HCC.


Current status of CAR-T cell therapy for pediatric hematologic malignancies.
Acute lymphoblastic leukemia (ALL) is the most common cancer in the pediatric population, and the long-term survival can reach 90%. However, approximately, 20% of pediatric ALL patients experience relapse and require second-line chemotherapy. This is frequently followed by hematopoietic stem cell transplantation, which can cause long-term sequelae. Recent advances in immunotherapy, such as monoclonal antibody therapy and chimeric antigen receptor (CAR)-T cell therapy, have revolutionized the treatment of relapsed and refractory ALL. Anti-CD19 CAR-T cells successfully eliminate B cell malignancies such as ALL. Tisagenlecleucel (Kymriah®) is the first CAR-T cell immunotherapy approved by the FDA. CAR-T cell therapy can cause specific adverse events (AEs) such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, which are defined and graded according to the consensus grading system and treated with supportive therapies along with tocilizumab and corticosteroids. Other AEs include prolonged bone marrow suppression and hypogammaglobulinemia. Severe AEs are less common in the real-world experience than in clinical trials, probably due to better management of the patient before and during CAR-T cell therapy. The biggest challenge in CAR-T cell therapy against ALL is relapse. A high tumor burden on infusion, early loss of B cell aplasia, and minimal residual disease positivity after CAR-T cell infusion are predictive of relapse. Consolidative stem cell transplantation may improve the long-term outcome. The success of CD19 CAR-T cell therapy against B cell malignancy prompted extensive research into the use of CAR-T cells against other hematologic malignancies such as T cell leukemia or myeloid leukemia.


The effect of an oral leukotriene D4 antagonist L-649,923 on the response to inhaled antigen in asthma.
We have compared the effects of the leukotriene (LT) D4 antagonist L-649,923 and placebo on the airway response to antigen challenge in eight men with mild asthma known to have both an early and late response to inhaled antigen. Subjects ingested 1000 mg of L-649,923 or placebo in a randomized, double-blind protocol and, two hours later, inhaled the dose of antigen known to induce a 20% fall in FEV1. Pulmonary function (specific conductance, FEV1, peak expiratory flow rate, and maximal flow at 25% of vital capacity) was measured at intervals before and up to 9 hours after antigen. FEV1 fell in one subject after L-649,923 ingestion. L-649,923 in the other seven subjects caused no change in baseline pulmonary function, a small reduction in the early response to antigen for FEV1, peak expiratory flow rate, and maximal flow at 25% of vital capacity but not for specific airway conductance (six subjects only) and no effect on the late response. The mean maximum fall in FEV1 in the early response was 1.35 L after L-649,923 ingestion and 1.78 after placebo ingestion. This relatively small degree of protection by L-649,923 suggests either that L-649,923 is not a sufficiently potent antagonist to diminish the effect of endogenous LTD4 in vivo or that LTD4 does not play a major role in the airway response to antigen challenge.


Effect of xylene inhalation on fixed-ratio responding in rats.
The effect of xylene inhalation was studied on operant behavior under a fixed-ratio (FR24) schedule in rats. Experiments were performed while rats were being exposed to xylene vapor in an inhalational (flow-through) behavioral chamber. Rats were exposed successively to three graded concentrations (113, 216 and 430 ppm) of xylene vapor each for 2 hr in range-finding studies during 6 1/4-hr sessions. The reinforcement rate which is correlated with FR responding was shown to be decreased at hr 1, hr 3 and hr 5. However at hr 2, hr 4 and hr 6 the reinforcement rate in rats increased approaching the control levels, thereby indicating development of tolerance. When rats were exposed to one of the three graded concentrations of xylene for 2 hr on separate days, they also showed a decrease in the reinforcement rate at hr 1; development of acute tolerance was also noted in this schedule. Exposure to the lowest (98.5 ppm) level of xylene used during 5-hr sessions caused no significant decrease in the reinforcement rate. This study thus attempts to identify a minimum effective concentration of xylene and indicates the development of acute tolerance to behavioral effect of xylene.


Seasonal changes in suicide in the United States, 1971 to 2000.
The seasonality of suicides in the USA increased from the 1970s to the 1990s. A significant proportion of suicide variation due to the seasonal component has been reported. Noted increments in seasonal rhythms in the latter part of the 1980s and 1990s seem to support those of Warren, et al. but contradict the conclusions of diminishing drawn by Hakko, et al., Rhimer, et al., and Yip, et al.


Evaluating the relationship between gait and clinical measures of plantar flexor function.
Individuals with plantar flexor weakness often require rehabilitation and/or orthoses, which should be personalized based on level of weakness. While plantar flexor weakness can be measured via peak plantar flexion moment during gait (MGAIT), motion analysis systems are often not clinically available. Clinical measures, such as the single-leg heel rise (SLHR) test and isometric muscle test, may provide surrogate measures of plantar flexor function during gait. However, it is currently unknown if a relationship(s) exists between such measures. This study evaluated the relationship between gait and clinical measures of plantar flexor function for typical individuals. Twenty-four participants underwent an instrumented gait analysis, from which MGAIT was calculated. Next, participants performed an isometric plantar flexor test, from which the maximum plantar flexion moment (MISO) was calculated. Finally, participants performed a SLHR test, from which maximum plantar flexion moment (MSLHR) and total work (Wtot_SLHR) were calculated. Via Pearson correlations, MSLHR was most strongly correlated to MGAIT (r = 0.56; p = 0.005). Wtot_SLHR was significantly correlated to MGAIT (r = 0.47; p = 0.019). MISO was not significantly correlated to MGAIT (r = 0.19; p = 0.363). MSLHR and/or Wtot_SLHR may provide clinically-feasible surrogate measures of plantar flexor function during gait.


Interfacial properties and structure stability of the gp41 tryptophan-rich peptide from HIV-1.
The HIV-1 envelope glycoprotein 41 (gp41) undergoes large-scale conformational changes in order to induce the fusion of the virus and cell membranes. Thus, we investigated a possible structure transit at the air-water interface for the tryptophan-rich peptide of gp41 (gp41W). The synthetic peptide (KWASLWNWFNITNWLWYIK), corresponding to gp41W, shows interfacial properties on pure water and Tris buffer at pH 8.5. Isotherm measurements and Brewster angle microscopy (BAM) imaging showed that the behavior of the peptide monolayer was dependent on the subphase composition. A homogenous film was formed on buffer during the peptide monolayer compression, while the appearance of condensed domains on pure water could indicate the oligomerization of gp41W during the surface pressure increase. Polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS) showed that, whatever the subphase, gp41W adopts an α-helix structure at the air-water interface and does not transit for any other structure even at high surface pressures.


Gene expression profiling of renal cell carcinoma: a DNA macroarray analysis.
To examine differences in gene expression levels between renal cell carcinoma (RCC) tissue and 'normal' appearing renal tissue using a commercially available DNA macroarray. Tissue was obtained from 47 consecutive radical nephrectomies, 29 of which were eligible. DNA macroarrays were analysed on the tumour and normal-appearing control tissue to measure the expression of 1185 cancer-related genes. The group of samples was also stratified according to the presence or absence of granular cells and according to tumour grade. Quantitative real-time polymerase-chain reaction (PCR) was also performed on seven key genes present on the macroarray. In all, 444 genes were over-expressed and 33 genes were under-expressed. Using selection criteria reduced the list to nine that were significantly over-expressed and 23 that were under-expressed. These significant genes belonged to the families of oncogenes, growth factors, interleukins, receptors, immune system components, cytoskeleton, matrix proteins and intracellular modulators, or they coded for proteins involved in DNA transcription and RNA translation, DNA repair, protein turnover, and metabolism of carbohydrates and lipids. There were differences in gene expression according to the presence or absence of granular cells and according to tumour grade. Using quantitative real-time PCR there was over-expression of epidermal growth factor receptor, c-myc, transforming growth factor-alpha, vascular endothelial growth factor and vimentin, and under-expression of TYRO3 protein tyrosine kinase. The von Hippel-Lindau gene was under-expressed but not significantly. A procedure for collecting and storing fresh renal tissue and subsequent gene expression profiling of RCC and normal renal tissue was established. A commercially available DNA macroarray coupled with the significance analysis of macroarrays allowed the identification of sets of differentially expressed cancer-related genes that were characteristic of RCC, compared with apparently normal renal tissue, and which distinguished among subgroups divided according to tumour grade and histological subtype. Quantitative PCR is important to validate the results of macroarray experiments.


Ultrahigh pressure liquid chromatography-(tandem) mass spectrometry in human sports drug testing: possibilities and limitations.
Doping control analytical laboratories for human sports predominantly employ nowadays chromatographic-mass spectrometric test methods for routine, high throughput screening and confirmation assays concerning low and high molecular mass analytes. Liquid chromatography-(tandem) mass spectrometry [(LC-MS(/MS)] and particularly ultrahigh pressure liquid chromatography (UHPLC)-MS/MS instruments have become devices of choice due to their indispensable capabilities that compensate for limitations inherent to other commonly used strategies such as immunological and gas chromatography-(tandem) mass spectrometry [(GC-MS(/MS)]-based detection methods. UHPLC-MS/MS-based assays at low mass spectrometric resolution have been established allowing for fast and sensitive targeted analyses focusing on pre-selected target analytes with diagnostic precursor-product ion pairs. Combining UHPLC to high resolution/high accuracy MS(/MS) further expanded the targeted approach (i.e., plotting extracted ion chromatograms of protonated or deprotonated molecules as well as product ions measured with accurate masses) toward non-targeted analyses enabling also retrospective data mining. In this review, recent applications of UHPLC-MS/MS in sports drug testing procedures published between 2008 and 2012 are presented and advantages as well as limitations in a short- and long-term perspective are discussed.


The prevalence of wound management physical therapist practice in the state of Texas.
Wound management has become one of the ten physical therapy (PT) certification specialty areas. With this advanced clinical designation opportunity, more PT specialists and residencies with integumentary and wound management expertise will be needed for the educational and practice training of future specialists. The purpose of this study was to characterize wound management practice by licensed physical therapists in Texas. A Qualtrics survey was distributed to 19,159 licensed physical therapists. The questionnaire contained 23 questions that inquired into the subject's professional background, clinical experience, and opinions of wound care practice. The response rate was 9.6% (n = 1,839) and 1,643 respondents indicated that they were currently practicing. Although 69.1% of active physical therapists (n = 1,136) stated that they had practiced wound care at some point of their career, most of them do not practice wound care anymore and their reasons were discussed. Of those active physical therapists, 41.3% (n = 679) of them reported wound care was being practiced in their facilities, but only 18.3% (n = 311) directly practiced wound care. The respondents felt that the prevalence of wound management physical therapists practice over the last five years has been decreasing. The current prevalence of wound management practice is low and a decreasing trend of PT practice in wound care was observed in Texas. A limitation of this study is the low response rate. Future studies across different regions of the country are warranted.


Detection and monitoring of minimal residual disease by quantitative real-time PCR.
The detection of malignant cells by quantitative real-time PCR has become state of the art for diagnosis, monitoring response to treatment and detection of minimal residual disease (MRD) in patients with leukemia or lymphoma. In order to be used in high-throughput analyses technical details have to be standardized to improve reproducibility and comparability of quantitative results obtained in different laboratories. Molecular monitoring of disease activity during and after treatment based on the detection of malignant cells in circulation or bone marrow by quantitative real-time PCR will be helpful to develop individualized treatment strategies for every patient. The effectiveness of any kind of innovative treatment with specific antibodies, cellular immunotherapy or molecules designed for specific targets of tumor cells can be controlled at a very high level of sensitivity and accuracy. Based on quantitative results indicative for success or treatment failure, therapeutic changes upon the detection of progressive disease at the molecular level can be made even before symptoms or signs of clinical relapse occur. Hopefully, this will lead to higher cure rates and improved long-term survival.


Social isolation impairs oral palatal wound healing in sprague-dawley rats: a role for miR-29 and miR-203 via VEGF suppression.
To investigate the effects of social isolation on oral mucosal healing in rats, and to determine if wound-associated genes and microRNAs (miRNAs) may contribute to this response. Rats were group housed or socially isolated for 4 weeks before a 3.5 mm wound was placed on the hard oral palate. Wound closure was assessed daily and tissues were collected for determination of gene expression levels and miRNAs (i.e., miR-29a,b,c and miR-203). The predicted target of these microRNAs (i.e., vascular endothelial growth factor A, VEGFA) was functionally validated. Social isolation stress delayed the healing process of oral palatal mucosal wounds in rats. Lower mRNA levels of interleukin-1β (IL1β), macrophage inflammatory protein-1α (MIP1α), fibroblast growth factor 7 (FGF7), and VEGFA were found in the biopsied tissues of isolated animals on days 1 and/or 3 post-wounding. Intriguingly, the isolated rats persistently exhibited higher levels of miR-29 family members and miR-203. Our results confirmed that VEGFA is a direct target of these miRNAs, as both miR-29a,c and miR-203 strongly and specifically suppressed endogenous VEGFA expression in vitro. This study in rats demonstrates for the first time that social isolation delays oral mucosal healing, and suggests a potential role for healing-associated gene and miRNA interactions during this process via modulation of VEGF expression.


Concentration of selected metals in penguins and other representative fauna of the Antarctica.
Concentration of Zn, Cu, Cd, Pb, Ag, Co, Ni, Cr, Mn and Fe were determined in muscle and liver of three species of penguins and other animals of the antarctic region. Liver was characterized by maximum concentrations of all the metals analyzed. The element levels in the samples assayed are in keeping with those reported previously by other authors. It is assumed that specific food habits of penguins are mainly responsible for elevated Cd levels in livers of these birds.


Gastrocnemius muscle flap including Achilles tendon after extensive patellectomy for soft tissue sarcoma.
A 72-year-old man developed a soft-tissue sarcoma anterior to his left knee. The tumour was excised widely combined with an extensive patellectomy. A gastrocnemius flap including Achilles tendon was used successfully to cover the soft-tissue defect and to reconstruct the knee extensor mechanism.


Degradation of aniline by newly isolated, extremely aniline-tolerant Delftia sp. AN3.
A bacterial strain, AN3, which was able to use aniline or acetanilide as sole carbon, nitrogen and energy sources was isolated from activated sludge and identified as Delftiasp. AN3. This strain was capable of growing on concentrations of aniline up to 53.8 mM (5000 mg/l). Substituted anilines such as N-methylaniline, N, N-dimethylaniline, 2-methylaniline, 4-methylaniline, 2-chloroaniline, 3-chloroaniline, o-aminoaniline, m-aminoaniline, p-aminoaniline, and sulfanilic acid did not support the growth of strain AN3. The optimal temperature and pH for growth and degradation of aniline were 30 degrees C and 7.0, respectively. The activities of aniline dioxygenase, catechol 2,3-dioxygenase and other enzymes involved in aniline degradation were determined, and results indicated that all of them were inducible. The K (m) and V (max) of aniline dioxygenase were 0.29 mM and 0.043 mmol/mg protein/min, respectively. The K (m) and V (max) of catechol 2, 3-dioxygenase for catechol were 0.016 mM and 0.015 mmol/mg protein/min, respectively. Based on the results obtained, a pathway for the degradation of aniline by Delftiasp. AN3 was proposed. The importance of the strain to the operation of municipal wastewater treatment plants is discussed.


Ultrasonic esophagoprobe for TNM staging of highly stenosing esophageal carcinoma.
Endosonographic staging of esophageal carcinoma may be limited in one third of cases by tumor stenoses that cannot be traversed with conventional echoendoscopes. We designed and evaluated a new endosonographic instrument (ultrasonic esophagoprobe) for TNM staging of highly stenosing esophageal carcinomas. Eighty-seven consecutive patients (64 men, mean age 61 years) with highly stenosing esophageal carcinomas were studied with the esophagoprobe (features: diameter of 7.9 mm, bougie-shaped tip, no fiber optics, insertion over a guide wire). The esophagoprobe was successfully inserted past the stenosis without complication in all patients. Nine patients (10%) required preliminary bougienage to 33 F. The imaging quality was high and allowed for complete T and N staging in all patients. M staging was indeterminate in 15 patients because of inadequate visualization of the celiac axis region. Histopathologic correlation in 38 patients who underwent surgery showed an overall T stage accuracy rate of 89% (T2 = 80%, T3 = 95%, T4 = 87%), and N and M stage accuracies of 79% (N0 = 44%, N1 = 90%) and 91% (M0 = 94%, M1 = 75%), respectively. The esophagoprobe enables safe passage of highly stenosing esophageal carcinomas for TNM staging. Accuracy rates are similar to those reported for conventional echoendoscopes.


Vulnerability and Entitlements.
The article examines the merits of both human rights and citizenship as systems to protect vulnerable individuals. The idea of vulnerability is presented as a more reliable concept than the dignity of the individual in comparative research. The body is basic to vulnerability.


Metal-free single heteroatom (N, O, and B)-doped coconut-shell biochar for enhancing the degradation of sulfathiazole antibiotics by peroxymonosulfate and its effects on bacterial community dynamics.
Metal-free single heteroatom (N, O, and B)-doped coconut-shell biochar (denoted as N-CSBC, O-CSBC, and B-CSBC, respectively) were fabricated in a one-step pyrolysis process to promote peroxymonosulfate (PMS) activation for the elimination of sulfathiazole (STZ) from aquaculture water. B-CSBC exhibited remarkably high catalytic activity with 92% of STZ degradation in 30 min attributed to the presence of meso-/micro-pores and B-containing functional groups (including B-N, B-C, and B2O3 species). Radical quenching tests revealed SO4•-, HO•, and 1O2 being the major electron acceptors contributing to STZ removal by PMS over B-CSBC catalyst. The B-CSBC catalyst has demonstrated high sustainability in multiple consecutive treatment cycles. High salinity and the presence of inorganic ions such as chloride, enhanced the performance of the sulfate radical-carbon-driven advanced oxidation processes (SR-CAOPs) as pretreatment strategy that significantly facilitated the removal of STZ from aquaculture water. Furthermore, a potential sulfonamide-degrading microorganism, Cylindrospermum_stagnale, belonging to the phylum Cyanobacteria, was the dominant functional bacteria according to the results of high-throughput 16S rRNA gene sequencing conducted after the B-CSBC/PMS treatment. This study provides new insights into the SR-CAOP combined with bioprocesses for removing STZ from aqueous environments.


Amino acid sequence diversity of the major human papillomavirus capsid protein: implications for current and next generation vaccines.
Despite the fidelity of host cell polymerases, the human papillomavirus (HPV) displays a degree of genomic polymorphism resulting in distinct genotypes and intra-type variants. The current HPV vaccines target the most prevalent genotypes associated with cervical cancer (HPV16/18) and genital warts (HPV6/11). Although these vaccines confer some measure of cross-protection, a multivalent HPV vaccine is in the pipeline that aims to broaden vaccine protection against other cervical cancer-associated genotypes including HPV31, HPV33, HPV45, HPV52 and HPV58. Both current and next generation vaccines comprise virus-like particles, based upon the major capsid protein, L1, and vaccine-induced, type-specific protection is likely mediated by neutralizing antibodies targeting L1 surface-exposed domains. The aim of this study was to perform an in silico analysis of existing full length L1 sequences representing vaccine-relevant HPV genotypes in order to address the degree of naturally-occurring, intra-type polymorphisms. In total, 1281 sequences from the Americas, Africa, Asia and Europe were assembled. Intra-type entropy was low and/or limited to non-surface-exposed residues for HPV6, HPV11 and HPV52 suggesting a minimal effect on vaccine antibodies for these genotypes. For HPV16, intra-type entropy was high but the present analysis did not reveal any significant polymorphisms not previously identified. For HPV31, HPV33, HPV58, however, intra-type entropy was high, mostly mapped to surface-exposed domains and in some cases within known neutralizing antibody epitopes. For HPV18 and HPV45 there were too few sequences for a definitive analysis, but HPV45 displayed some degree of surface-exposed residue diversity. In most cases, the reference sequence for each genotype represented a minority variant and the consensus L1 sequences for HPV18, HPV31, HPV45 and HPV58 did not reflect the L1 sequence of the currently available HPV pseudoviruses. These data highlight a number of variant amino acid residues that warrant further investigation for vaccine and natural history studies of HPV.


Nigral-specific increase in ser31 phosphorylation compensates for tyrosine hydroxylase protein and nigrostriatal neuron loss: Implications for delaying parkinsonian signs.
Compensatory mechanisms that augment dopamine (DA) signaling are thought to mitigate onset of hypokinesia prior to major loss of tyrosine hydroxylase (TH) in striatum that occurs in Parkinson's disease. However, the identity of such mechanisms remains elusive. In the present study, the rat nigrostriatal pathway was unilaterally-lesioned with 6-hydroxydopamine (6-OHDA) to determine whether differences in DA content, TH protein, TH phosphorylation, or D1 receptor expression in striatum or substantia nigra (SN) aligned with hypokinesia onset and severity at two time points. In striatum, DA and TH loss reached its maximum (>90%) 7 days after lesion induction. However, in SN, no DA loss occurred, despite ∼60% TH loss. Hypokinesia was established at 21 days post-lesion and maintained at 28 days. At this time, DA loss was ∼60% in the SN, but still of lesser magnitude than TH loss. At day 7 and 28, ser31 TH phosphorylation increased only in SN, corresponding to less DA versus TH protein loss. In contrast, ser40 TH phosphorylation was unaffected in either region. Despite DA loss in both regions at day 28, D1 receptor expression increased only in lesioned SN. These results support the concept that augmented components of DA signaling in the SN, through increased ser31 TH phosphorylation and D1 receptor expression, contribute as compensatory mechanisms against progressive nigrostriatal neuron and TH protein loss, and may mitigate hypokinesia severity.


Antimicrobial bowel preparation. Oral, parenteral, or both?
It has been suggested that wound infection rates after colorectal operations are influenced more by the presence of adequate tissue levels of antimicrobials at the time of contamination than by the extent of bacterial colonization of the intestinal lumen. There are, however, theoretical grounds for the belief that both levels are important. The authors therefore conducted a random control trial in 119 consecutive patients undergoing elective colorectal operations, comparing the results in a group receiving purely parenteral antimicrobial prophylaxis with those in one having a combined oral and parenteral regimen. The results in 83 contemporary nonrandomized patients, all of whom had the combined prophylactic regimen, are also reported. Oral bowel preparation resulted in a significantly smaller number of operation cultures showing growth of fecal gram-negative aerobes and anaerobes than did the purely parenteral regimen. There were more isolations of enterococci in the combined group but the excess did not achieve statistical significance. The rates of infective complications were higher in the parenteral than in the combined group, the difference in wound infection rates being statistically significant; the figures were 27.6 percent and 13.9 percent, respectively (P = .04). It is concluded that, in colorectal operations, it is advisable not only to ensure adequate tissue levels of antimicrobials but also to reduce the risk of endogenous bacterial infection by partially decontaminating the bowel.


Low cerebrovascular reserve capacity in long-term follow-up after subarachnoid hemorrhage.
Intradural arteries formerly in vasospasm after subarachnoid hemorrhage (SAH) show structural changes that result in arterial wall thickening and luminal narrowing. To evaluate if these changes lead to maldistribution of cerebral perfusion and reduced cerebrovascular reserve capacity (CVRC) in surviving patients, a long-term follow-up study of 18 adult patients after SAH was performed. Eighteen patients were selected for the study, all had shown vasospasm after an early operation on a ruptured aneurysm, were in good neurological condition (GOS [Glasgow Outcome Score] 4 or 5 ), and had no residual infarcts. A technetium-99m-hexamethyl-propylenamine oxime (HMPAO) single-photon emission computed tomography was performed 15 to 73 months after SAH. To study CVRC, a second investigation after application of acetazolamide was performed 1 week later. Single-photon emission computed tomography showed areas of focally reduced HMPAO uptake predominantly in the hemisphere ipsilateral to the vessels more affected by posthemorrhagic vasospasm. The thalamus and the basal ganglia, the frontal lobe, and the temporal lobe were the regions most frequently showing reduced uptake. The individual change of HMPAO uptake after acetazolamide application ranged from -7% to 44% (mean, 17% +/- 15%). These results show a remarkable reduction of CVRC compared with findings in healthy individuals. Based on these new findings, further investigations focusing on CVRC in routine SAH follow-up are worth being considered.


Seasonal variation in accelerometer-determined sedentary behaviour and physical activity in children: a review.
To undertake a review of the methods and findings of published research evaluating the influence of season on accelerometer-determined sedentary behaviour (SB) and physical activity (PA) in children. A literature search was carried out using PubMed, Embase, Medline and Web of Science up to, and including, June 2011. The search strategy focused on four key elements: children, SB or PA, season and accelerometer. Articles were eligible for inclusion if they were published in English, included healthy study participants aged ≤ 18 years, reported at least one outcome variable derived from accelerometer-determined measurements, and compared SB or PA between two or more seasons, or controlled for season of measurement. Eligible papers were reviewed and evidence tables compiled reporting on publication year, country studied, study recruitment, consent rate, sample descriptives, study design, accelerometer protocol, valid accelerometer data receipt, season definition, statistical methods and key findings. Sixteen of 819 articles were eligible for inclusion: children aged two to five years, six to twelve, or six to 18 years were included in five, six and five articles respectively. Six articles were from the UK, six from other European countries, three from the USA and one from New Zealand. Study sample sizes ranged from 64 to 5595. PA was reported in all articles but SB in only three. Only four studies were longitudinal and none of these reported SB. Seasonal variation in PA was reported in all UK studies, being highest in summer and lowest in winter. In four non-UK studies seasonal variation in PA was not found. Findings were inconclusive for SB. There is sufficient evidence to support public health interventions aimed at increasing PA during winter in UK children. No conclusions can be drawn regarding the effect of season on children's SB reflecting few studies of small sample size, lack of repeat measures, incomparable definitions of season and inconsistent accelerometer protocols. Future research should determine factors that drive seasonal patterns in PA and SB in children such as age, sex, and geographic and climatic setting to inform interventions and target populations.


The influence of food on the bioavailability of a slow release theophylline preparation.
Food-induced changes in the absorption of Theostat 300, a controlled release formulation of theophylline, have been studied in healthy volunteers. This open, randomised, 3-way, single-dose study involved 12 volunteers who received the drug either while fasting, or with a standardised low-fat (10g), or high-fat (60g) breakfast. Each subject was studied over a 3-week period, with 3 separate days of oral treatment and a 7-day washout period between treatments. The results showed no differences in AUC0-24 and tmax values between the 3 kinds of diet. The only differences observed concerned absorption. Food intake increased Cmax values by 20%. The steady-state peak concentration obtained by means of simulated plasma levels was not influenced by food intake. This slight food-drug interaction of Theostat 300 seemed to be of no clinical significance.


Extraction and preliminary characterization of a human bronchogenic carcinoma antigen.
Saline extracts of human bronchogenic tumours, soluble in 50% saturated ammonium sulphate and also fractions from Sephadex G-200 chromatography were used to raise antisera in rabbits. After absorbing the antisera with normal tissue extracts, direct Ouchterlony tests were performed against tumour (adenocarcinomata and squamous cell carcinomata) and normal extracts. A precipitin reaction was given with all 11 tumour extracts tested at a concentration of 5 mg/ml whereas all the 9 normal lung control extracts did not react at concentrations up to 100 mg/ml. The possibility that this reaction could be related to histocompatibility differences between individuals is ruled out by the fact that in two cases tumour and normal tissue were obtained from the same patient. These studies and also precipitin-inhibition experiments have confirmed the existence of antigen associated with bronchial carcinomata and have shown that, although the antigen or a cross-reacting antigen is present in normal lung tissue, the amounts are small in comparison with the amounts extracted from tumour. Antigenic activity was contained in a single absorbance peak when fractionated by Sephadex G-200 chromatography and its elution volume indicated a molecular weight of approximately 4-0 times 10(4)D. Further purification was achieved using isotachophoresis. Preliminary characterization of the antigen has shown it to be stable at pH 4-5, resistant to heating at 50 degrees C for 30 min, to migrate on immunoelectrophoresis with a cationic mobility at PH 8-5 and to be immunologically distinct from carcinoembryonic antigen.