Patterns of outcome following recurrence after myeloablative therapy with autologous bone marrow transplantation for follicular lymphoma.
To assess the patterns of recurrence, management, and survival following recurrence after myeloablative therapy with autologous bone marrow transplantation (ABMT) in patients with follicular lymphoma (FL). Between June 1985 and October 1995, 99 patients with FL received cyclophosphamide and total-body irradiation with ABMT as consolidation of second or subsequent remission. Median length of follow-up was 5 1/2 years, and 33 patients developed recurrent lymphoma a median of 14 months after ABMT. In 26 patients, the recurrence was overt; in seven, it was detected on surveillance investigation. Twenty-six patients presented with recurrence at previous sites of disease. Twenty-two patients (67%) had FL at the time of recurrence; in 11 (33%), there was evidence of transformation to diffuse large B-cell lymphoma. Eight patients were managed expectantly; five were alive 21 to 53 months later. Twenty-five patients have required treatment to date; eight remained alive 6 months to 10 years later, and five were in remission. The Kaplan-Meier estimate of patients alive 5 years after recurrence is 45% (95% confidence interval, 27% to 62%). In univariate and multivariate analyses, survival after recurrence and overall survival after diagnosis were similar to those of a historical control group who received conventional treatment, before the introduction of myeloablative therapy (adjusted hazard ratio [HR], 1.56, P = .3, and HR, 1.34, P = .4, respectively). The survival pattern of patients with FL following recurrence after myeloablative therapy and ABMT suggests that this treatment does not compromise outcome in patients in whom it fails, reflecting the survival pattern of the disease when treated conventionally.


The influence of the genetic and non-genetic factors on bone mineral density and osteoporotic fractures in Chinese women.
To investigate the effects of genetic and non-genetic factors on bone mineral densities (BMDs) and osteoporotic fractures. This was a cross-sectional study to investigate the relationships between 18 SNPs and non-genetic factors with BMDs and osteoporotic fractures in 1012 Chinese Han women. Five SNPs in genes GPR177, CTNNB1, MEF2C, SOX6, and TNFRSF11B were associated with L1-4 or total hip BMDs. rs11898505 in SPTBN1 gene was associated with osteoporotic fractures. Subjects carrying the largest number of risk alleles (highest 10 %) not only had lower BMD values as compared to those carrying the least number of risk alleles (lowest 10 %), they also had a higher risk of fracture [P = 0.002, OR = 2.252, 95 %CI (1.136, 4.463)]. Results from multivariate stepwise regression analysis revealed that age [P < 0.001, OR = 1.038, 95 % CI (1.018, 1.058)], number of falls in a year [P < 0.001, OR = 2.347, 95 % CI (1.459, 3.774)], the G risk allele in rs11898505 [P = 0.023, OR = 1.559, 95 % CI (1.062, 2.290)], and the L1-4 BMD [P = 0.017, OR = 0.286, 95 % CI (0.102, 0.798)] were associated with the occurrence of osteoporotic fractures. Genetic (rs11898505) and non-genetic factors (age, number of falls in a year and L1-4 BMD) could work in concert to contribute to the risk of osteoporotic fractures.


Levels of Pb and Cd in Single Feeding Stuffs and Compound Feeds for Poultry.
The assessment of heavy metals in feeds for food-producing animals is of particular importance both for animal and human health. Single feeds can be mixed and offered to animals either crushed or pelleted, and it would be recommendable to assess heavy metal content before mixing. A total of 408 feed samples for poultry were sent to our laboratory by farmers and feed manufacturers from Germany. Single feeding stuffs (cereals and legume seeds, n = 109 and n = 86, respectively) and compound mixed feeds for laying hens (n = 63), broilers (n = 83) and turkeys (n = 67) in the years 2015 to 2018 were processed for Pb and Cd content. Analyses pointed to the lowest Pb contents in cereal feeds (0.031 and 0.101 mg/kg feed). In compound feeds, values ranged between 0.089 (broilers) and 0.181 mg/kg on an as fed basis (laying hens). The highest Pb content of 0.358 mg/kg (as fed) was determined in one sample of mixed feed for turkeys. Cd levels in cereal feeds and compound feeds were similar; Cd in legume seeds turned out to be slightly higher (0.089 mg/kg feed). Results point to differences between cereals and legume seeds as single feeds; however, safe levels were found for both, as well as for compound feeds, below the maximum permitted for Pb 10 mg/kg and Cd 1 mg/kg in feed dry matter (88%).


Healthcare Professionals' Views on Parental Participation in the Neonatal Intensive Care Units.
To examine the associations between age, gender, and profession in relation to the perceived importance of parental participation in Neonatal Intensive Care Units. A quantitative cross-sectional design was used. Participants were recruited consecutively from all 40 existing NICU units in Sweden. A total of 443 healthcare professionals (372 nurses and 71 physicians) participated in the study. Participants completed the Swedish version of the Empowerment of Parents in the Intensive Care-Neonatology (EMPATHIC-N) questionnaire. Data were analyzed using multiple regression analyses. The findings indicated that profession and age, but not gender, had an overall perceived importance on how nurses and physicians rated specific aspects of parental participation in NICUs. Being a nurse, compared to a physician, was associated with an increase in overall perceived importance of parental participation in NICUs. These differences may affect and may be crucial for how parents take a part in the care of their infant and also for how they adapt to the parental role. Nurses and physicians require education and training that support parental participation based on age and their different roles, rather than simply conveying information about the technical medical aspects of NICU care. For a sustainable outcome all team members should be invited to discuss cases from their perspectives.


[Application of food allergens specific IgG antibody detection in chronic diarrhea in children].
The causes of chronic diarrhea in children are complex. At present, food allergy is generally viewed as an important cause of this disorder, and IgG-mediated delayed allergy plays a major role in this process. This study aimed to explore the link between food specific IgG and chronic diarrhea in children, as well as the value of food allergens-specific IgG antibody detection in the management of this disorder. Eighty-two children with chronic diarrhea and 30 healthy controls were enrolled. Serum levels of specific IgG antibody to 14 kinds of food were detected using ELISA. The results were classified into four grades: Grade 0 (negative), Grade 1 (mild allergy), Grade 2 (moderate allergy) and Grade 3 (severe allergy). The patients received a diet treatment based on the results of food specific IgG antibody detection. Children with negative IgG antibody were allowed to continue their current diet. In children with Grade 1 allergy, the food responsible for the IgG antibody positive test was given only at an interval of four days. In children with Grade 2 or 3, the offending food was eliminated from the diet. Of the 82 children with chronic diarrhea, 79 (96.2%) had increased specific IgG levels for one or more of the 14 foods tested compared to 8 (26.7%) of the controls (P <0.01). The majority of patients showed increased specific IgG levels for milk (68.3%) and egg (62.2%). A low proportion of patients (2.4%) was allergic to chicken, and no patient was allergic to pork. The symptoms were improved in 65 patients (79.3%) after 1 week to 3 months of diet treatment. Food allergy is one of major causes of chronic childhood diarrhea. Food specific IgG antibody detection may assist in the dietary management of this disorder.


Chemoprevention of chemically induced skin tumorigenesis by ligand activation of peroxisome proliferator-activated receptor-beta/delta and inhibition of cyclooxygenase 2.
Ligand activation of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) and inhibition of cyclooxygenase-2 (COX2) activity by nonsteroidal anti-inflammatory drugs (NSAID) can both attenuate skin tumorigenesis. The present study examined the hypothesis that combining ligand activation of PPARβ/δ with inhibition of COX2 activity will increase the efficacy of chemoprevention of chemically induced skin tumorigenesis over that observed with either approach alone. To test this hypothesis, wild-type and Pparβ/δ-null mice were initiated with 7,12-dimethylbenz[a]anthracene (DMBA), topically treated with 12-O-tetradecanoylphorbol-13-acetate to promote tumorigenesis, and then immediately treated with topical application of the PPARβ/δ ligand GW0742, dietary administration of the COX2 inhibitor nimesulide, or both GW0742 and nimesulide. Ligand activation of PPARβ/δ with GW0742 caused a PPARβ/δ-dependent delay in the onset of tumor formation. Nimesulide also delayed the onset of tumor formation and caused inhibition of tumor multiplicity (46%) in wild-type mice but not in Pparβ/δ-null mice. Combining ligand activation of PPARβ/δ with dietary nimesulide resulted in a further decrease of tumor multiplicity (58%) in wild-type mice but not in Pparβ/δ-null mice. Biochemical and molecular analysis of skin and tumor samples show that these effects were due to the modulation of terminal differentiation, attenuation of inflammatory signaling, and induction of apoptosis through both PPARβ/δ-dependent and PPARβ/δ-independent mechanisms. Increased levels and activity of PPARβ/δ by nimesulide were also observed. These studies support the hypothesis that combining ligand activation of PPARβ/δ with inhibition of COX2 activity increases the efficacy of preventing chemically induced skin tumorigenesis as compared with either approach alone.


Feline Exocrine Pancreatic Insufficiency: A Retrospective Study of 150 Cases.
Little information is available about the clinical presentation and response to treatment of cats with exocrine pancreatic insufficiency (EPI). To describe the signalment, clinical signs, concurrent diseases, and response to treatment of cats with EPI. One hundred and fifty cats with EPI. Retrospective case series. Questionnaires were sent to 261 veterinarians, and 150 (57%) were returned with data suitable for statistical analysis. The median age of the cats with EPI was 7.7 years. The median body condition score was 3 of 9. Ninety-two of 119 cats (77%) had hypocobalaminemia, and 56 of 119 cats (47%) had increased and 6 of 119 cats (5%) had decreased serum folate concentrations. Clinical signs included weight loss (91%), unformed feces (62%), poor hair coat (50%), anorexia (45%), increased appetite (42%), lethargy (40%), watery diarrhea (28%), and vomiting (19%). Eighty-seven cats (58%) had concurrent diseases. Treatment response was reported to be good in 60%, partial in 27%, and poor in 13% of 121 cats. Trypsin-like immunoreactivity <4 μg/L was associated with a positive response to treatment (OR, 3.2; 95% CI, 1.5-7.0; P = .004). Also, cobalamin supplementation improved the response to treatment (OR, 3.0; 95% CI, 1.4-6.6; P = .006). Exocrine pancreatic insufficiency in cats often has a different clinical presentation than in dogs. The age range for EPI in cats is wide, and many cats can be ≤5 years of age. Most cats respond well to appropriate treatment for EPI, and cobalamin supplementation appears to be necessary for a good response.


Developing an occupational therapy curriculum at a small college.
Small colleges and universities are increasingly turning to new program development to increase enrollments, stem decline, and ensure survival. Occupational therapy is an increasingly popular curriculum among small college and university administrators in view of its potential for attracting students, enhancing the organization's profile and mission, and generating revenue. This study examined the development of the occupational therapy curriculum at College Misericordia, Dallas, Pennsylvania, from 1981 to 1984. Interviews and pertinent documents, such as financial records, curricular materials, and enrollment statistics, were analyzed. The results demonstrate that the occupational therapy curriculum was instrumental in increasing enrollments and generating revenues at this small college. It can be concluded that curriculum development in occupational therapy can have a positive effect on an organization's ability to remain viable in an increasingly competitive market.


Level of agitation of psychiatric patients presenting to an emergency department.
The primary purpose of this study was to determine the level of agitation that psychiatric patients exhibit upon arrival to the emergency department. The secondary purpose was to determine whether the level of agitation changed over time depending upon whether the patient was restrained or unrestrained. An observational study enrolling a convenience sample of 100 patients presenting with a psychiatric complaint was planned, in order to obtain 50 chemically and/or physically restrained and 50 unrestrained patients. The study was performed in summer 2004 in a community, inner-city, level 1 emergency department with 45,000 visits per year. The level of patient agitation was measured using the Agitated Behavior Scale (ABS) and the Richmond Agitation-Sedation Scale (RASS) upon arrival and every 30 minutes over a 3-hour period. The inclusion criteria allowed entry of any patient who presented to the emergency department with a psychiatric complaint thought to be unrelated to physical illness. Patients who were restrained for nonbehavioral reasons or were medically unstable were excluded. 101 patients were enrolled in the study. Of that total, 53 patients were not restrained, 47 patients were restrained, and 1 had incomplete data. There were no differences in gender, race, or age between the 2 groups. Upon arrival, 2 of the 47 restrained patients were rated severely agitated on the ABS, and 13 of 47 restrained patients were rated combative on the RASS. There was a statistical difference (p = .01) between the groups on both scales from time 0 to time 90 minutes. Scores on the agitation scales decreased over time in both groups. One patient in the unrestrained group became unarousable during treatment. This study demonstrated that patients who were restrained were more agitated than those who were not, and that agitation levels in both groups decreased over time. Some restrained patients did not meet combativeness or severe agitation criteria, suggesting either that use of other criteria is needed or that restraints were used inappropriately. Further study of the level of agitation and the effects of restraints is needed.


ETS transcription factors control transcription of EZH2 and epigenetic silencing of the tumor suppressor gene Nkx3.1 in prostate cancer.
ETS transcription factors regulate important signaling pathways involved in cell differentiation and development in many tissues and have emerged as important players in prostate cancer. However, the biological impact of ETS factors in prostate tumorigenesis is still debated. We performed an analysis of the ETS gene family using microarray data and real-time PCR in normal and tumor tissues along with functional studies in normal and cancer cell lines to understand the impact in prostate tumorigenesis and identify key targets of these transcription factors. We found frequent dysregulation of ETS genes with oncogenic (i.e., ERG and ESE1) and tumor suppressor (i.e., ESE3) properties in prostate tumors compared to normal prostate. Tumor subgroups (i.e., ERG(high), ESE1(high), ESE3(low) and NoETS tumors) were identified on the basis of their ETS expression status and showed distinct transcriptional and biological features. ERG(high) and ESE3(low) tumors had the most robust gene signatures with both distinct and overlapping features. Integrating genomic data with functional studies in multiple cell lines, we demonstrated that ERG and ESE3 controlled in opposite direction transcription of the Polycomb Group protein EZH2, a key gene in development, differentiation, stem cell biology and tumorigenesis. We further demonstrated that the prostate-specific tumor suppressor gene Nkx3.1 was controlled by ERG and ESE3 both directly and through induction of EZH2. These findings provide new insights into the role of the ETS transcriptional network in prostate tumorigenesis and uncover previously unrecognized links between aberrant expression of ETS factors, deregulation of epigenetic effectors and silencing of tumor suppressor genes. The link between aberrant ETS activity and epigenetic gene silencing may be relevant for the clinical management of prostate cancer and design of new therapeutic strategies.


Impedance spectroscopy of ions at liquid-liquid interfaces.
The possibility to extract properties of an interface between two immiscible liquids, e.g., electrolyte solutions or polyelectrolyte multilayers, by means of impedance spectroscopy is investigated theoretically within a dynamic density-functional theory which is equivalent to the Nernst-Planck-Poisson theory. An approach based on a two-step fitting procedure of an equivalent circuit to impedance spectra is proposed which allows us to uniquely separate bulk and interfacial elements. Moreover, the proposed method avoids overfitting of the bulk properties of the two liquids in contact and underfitting of the interfacial properties, as they might occur for standard one-step procedures. The key idea is to determine the bulk elements of the equivalent circuit in a first step by fitting corresponding subcircuits to the spectra of uniform electrolyte solutions, and afterwards fitting the full equivalent circuit with fixed bulk elements to the impedance spectrum containing the interface. This approach is exemplified for an equivalent circuit which leads to a physically intuitive qualitative behavior as well as to quantitatively realistic values of the interfacial elements. The proposed method is robust such that it can be expected to be applicable to a wide class of systems with liquid-liquid interfaces.


Understandings of gender and HIV in the South African media.
It is widely agreed empowering women to take control of their lives and sexual health is a key strategy for tackling gender inequalities and HIV/AIDS, but to date this has been exceedingly difficult to achieve. This paper explores how a sample of South African media represent the relationship between gender and HIV/AIDS in the interests of understanding the symbolic context in which HIV/AIDS programmers conduct their work. The starting assumption is that representations of gender and HIV in the symbolic sphere provide the context within which people charged with designing and implementing women's empowerment interventions--government officials and NGO programme managers--construct understandings of this relationship and how best to tackle it. Content analysis was conducted on four South African newspapers between 1 January 2007 and 31 December 2008. Newspapers selected are widely read by "opinion leaders"; government officials and NGO programme managers. It is accepted that women's empowerment needs to involve top-down and bottom-up approaches. Dominant media representations portray women's empowerment as almost entirely a top-down process in which powerful actors are responsible for identifying and implementing women-focused interventions. Newspapers pay little attention to the need for the mobilisation of women via bottom-up programmes. Furthermore, while the media focuses on structural- and individual-level interventions, there is limited discussion of the importance of community-development interventions. Community-development interventions emphasise the need to build and support community-led responses to HIV. For women's empowerment to be successful interventions need to be at all levels. Currently, much emphasis is placed on the need for "socially responsible" media reporting in South Africa that supports positive social development and social justice. Against this background, we conclude media representations of appropriate ways to tackle gender and HIV/AIDS are limiting in ways that undermine awareness of the need for community-led interventions to empower women.


Precision in gynecologic cytologic interpretation: a study from the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology.
Numerous studies address the accuracy or positive predictive value of cytologic interpretations for defined histopathologic entities. The reproducibility (precision) of cytologic interpretation is less well defined. To establish and compare the reproducibility (precision) of cytologic interpretation in gynecologic cytopathology, as reflected in the educational program of the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology (PAP). The pathologists' interpretations for both validated (25 745 responses) and educational conventional (14 353 responses) slides in the PAP program for 2001 were analyzed. The frequency of exact matches between the reference and pathologists' interpretation for each of the cytologic interpretative categories was identified, and the cumulative distributions of exact match rates were derived. chi2 Tests by reference interpretations were used for cytodiagnostic categories, least and most reproducible groupings, and high-grade (HSIL) versus low-grade (LSIL) squamous intraepithelial lesions. Pathologists' interpretations of negative, Candida, Trichomonas, herpes, and LSIL were characterized by a high degree of exact matching, while interpretations of repair, HSIL, adenocarcinoma, and squamous cell carcinomas were characterized by a lesser degree of exact matching (reproducibility). Pathologists' cytologic interpretations of HSIL were significantly less reproducible than those of LSIL. The cytologic interpretations of the most significant categories (HSIL, squamous cell carcinoma, and adenocarcinoma) are less precise than those of specific infection (Candida, Trichomonas, and yeast), negative, and LSIL categories. Cytologic interpretations of LSIL are made with greater precision than those of HSIL and may represent a more appropriate endpoint to measure the precision performance of gynecologic cytology laboratories.


Enhancing partner support to improve smoking cessation.
While many cessation programmes are available to assist smokers in quitting, research suggests that partner involvement may encourage long-term abstinence. The purpose of this review was to determine if an intervention to enhance partner support helps smoking cessation when added as an adjunct to a smoking cessation programme, and to estimate the size of any effect. For the most recent update, the search was limited to the Cochrane Tobacco Addiction Group Specialized Register. This was searched in December 2011. The Specialized Register includes reports of controlled trials of smoking cessation identified from electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) to Issue 4, 2011, MEDLINE to update 20110826, EMBASE to 2011 week 33, PsycINFO to 20110822 and Web of Science. The search terms used were smoking (prevention, control, therapy), smoking cessation, and support (family, marriage, spouse, partner, sexual partner, buddy, friend, co-habitees and co-worker). Randomized controlled trials of smoking cessation interventions that compared an intervention that included a partner support component with an otherwise identical intervention and reported follow-up of six months or longer. Two authors independently identified the included studies and extracted data using a structured form. A third author was consulted to aid in the resolution of discrepancies. Abstinence, biochemically validated if possible, was the primary outcome measure and was extracted at two post-treatment intervals: six to nine months and 12 months or greater. Partner Interaction Questionnaire and Support Provided Measure scores were also analysed to assess partner support. A fixed-effect model was used to pool relative risks from each study and estimate a summary effect. A total of 57 articles were identified for this review. Twelve articles (13 studies, > 2000 participants) met the inclusion criteria. The definition of partner varied between studies. All studies gave self-reported smoking cessation rates, but there was limited biochemical validation of abstinence. The pooled risk ratio for self-reported abstinence was 0.99 (95% confidence interval (CI) 0.84 to 1.15) at six to nine months and 1.04 (95% CI 0.87 to 1.24) at 12 months or more post-treatment. Of the eight studies that measured partner support at follow-up, only two studies reported a significant increase in partner support in the intervention groups. One study reported a significant increase in partner support in the intervention group, but smokers' reports of partner support received did not differ significantly in this study. In this review of randomized controlled trials of interventions designed to enhance partner support for smokers in cessation programmes, we failed to detect an increase in quit rates. Limited data from several of the trials suggest that these interventions also did not increase partner support. No conclusions can be made about the impact of partner support on smoking cessation. Additional studies with larger samples are needed to adequately explore the effects of partner support interventions for smoking cessation.


Can patient characteristics predict benefit from epidural corticosteroid injections for lumbar spinal stenosis symptoms?
Epidural corticosteroid injections are commonly used to treat back and leg pain associated with lumbar spinal stenosis. However, little is known about which patient characteristics may predict favorable responses. The aim was to identify patient characteristics associated with benefits from epidural injections of corticosteroid with lidocaine versus epidural injections of lidocaine only for lumbar spinal stenosis symptoms. This was a secondary analysis of Lumbar Epidural steroid injections for Spinal Stenosis randomized controlled trial data from 16 US clinical sites. Patients aged older than or equal to 50 years with moderate-to-severe leg pain and lumbar central spinal stenosis randomized to epidural injections of corticosteroids with lidocaine (n=200) or lidocaine only (n=200) were included. Primary outcomes were the Roland-Morris Disability Questionnaire (RMDQ) and 0 to 10 leg pain intensity ratings. Secondary outcomes included the Brief Pain Inventory Interference Scale and the Swiss Spinal Stenosis Questionnaire. At baseline, clinicians rated severity of patient spinal stenosis, and patients completed predictor and outcome measures. Patients completed outcome measures again 3 and 6 (primary end point) weeks after randomization/initial injection. Analysis of covariance was used with treatment by covariate interactions to identify baseline predictors of greater benefit from corticosteroid+lidocaine versus lidocaine alone. We also identified nonspecific (independent of treatment) predictors of outcomes. Among 21 candidate predictors and six outcomes, only one baseline variable predicted greater benefit from corticosteroid+lidocaine versus lidocaine only at 3 or 6 weeks. Compared with patients who rated their health-related quality of life as high on the EQ-5D Index, patients who rated it as poor had greater improvement with corticosteroid than with lidocaine only in leg pain at 6 (but not 3) weeks (interaction coefficient=2.94; 95% confidence interval [CI]=0.11-5.76; p=.04) and in RMDQ disability scores at 3 (but not 6) weeks (interaction coefficient=4.77, 95% CI= -0.04 to 9.59; p = .05). Several baseline patient characteristics predicted outcomes regardless of treatment assignment. Among 21 baseline patient characteristics examined, none, including clinician-rated spinal stenosis severity, were consistent predictors of benefit from epidural injections of lidocaine+corticosteroid versus lidocaine only.


Fabrication of cardiac patch with decellularized porcine myocardial scaffold and bone marrow mononuclear cells.
Tissue engineered cardiac grafts are a promising therapeutic mode for ventricular wall reconstruction. Recently, it has been found that acellular tissue scaffolds provide natural ultrastructural, mechanical, and compositional cues for recellularization and tissue remodeling. We thus assess the potential of decellularized porcine myocardium as a scaffold for thick cardiac patch tissue engineering. Myocardial sections with 2-mm thickness were decellularized using 0.1% sodium dodecyl sulfate and then reseeded with differentiated bone marrow mononuclear cells. We found that thorough decellularization could be achieved after 2.5 weeks of treatment. Reseeded cells were found to infiltrate and proliferate in the tissue constructs. Immunohistological staining studies showed that the reseeded cells maintained cardiomyocyte-like phenotype and possible endothelialization was found in locations close to vasculature channels, indicating angiogenesis potential. Both biaxial and uniaxial mechanical testing showed a stiffer mechanical response of the acellular myocardial scaffolds; however, tissue extensibility and tensile modulus were found to recover in the constructs along with the culture time, as expected from increased cellular content. The cardiac patch that we envision for clinical application will benefit from the natural architecture of myocardial extracellular matrix, which has the potential to promote stem cell differentiation, cardiac regeneration, and angiogenesis.


Simultaneous measurement method of total and self-interference for the volumetric thickness-profilometer.
A simultaneous measurement method for the total interference and self-interference of a sample is proposed. The proposed method is capable of making separate measurements of the thickness and surface profile of micro-patterned thin film. The system is an extension of a full-field wavelength scanning interferometer with a single acousto-optic tunable filter (AOTF) as a spectral imaging device. Separate measurements are realized via the polarization-sensitive diffraction of non-collinear acousto-optic interaction. That is, the diffraction angle of an AOTF is separated into different directions depending on the polarization state of the incident light. In so doing, the polarization states of a reference and a sample light were manipulated differently so that a single AOTF can generate the total interference and the self-interference signal in different directions simultaneously. Thus, a compact and light-efficient system is realized with an AOTF, a beam splitter and two CCDs. Thus, a compact system with light-efficiency of two to four times higher than the previously reported system is realized with an AOTF, a beam splitter and two CCDs. Details of the calibration procedures such as wavelength-frequency relation, image shift and registration between two CCDs are provided for the proposed setup. Experimental results are provided and compared to those using commercial equipment that demonstrate the efficiency of the proposed system for the high-speed measurements of the thickness and the surface profile of micro-patterned thin film.


Implications of the Mn:ligand ratio for Mn uptake by Glycine max L. plants fertilized with heptagluconate and gluconate complexes.
The environmental risk of the application of synthetic chelates has furthered the implementation of biodegradable complexes to correct manganese (Mn)-deficient plants. This study used the biodegradable ligands of heptagluconate (G7) and gluconate (G6) to test the influence of the Mn2+ :ligand ratio on their fertilizers' capacity to provide Mn to plants. The efficacy of these complexes to correct Mn-deficient soybean was evaluated in hydroponics and calcareous soil conditions and compared with the synthetic chelate EDTA (ethylenediaminetetraacetic acid). This study demonstrated that G7 was a biodegradable alternative to EDTA for supplying Mn, maintaining an adequate nutritional balance compared with G6, which reduced iron (Fe) uptake by the plants. The efficacy of the Mn complexes depended on both the ligand and the Mn:ligand ratio, with the 1:1 and 1:2 molar ratios of Mn2+ :G7 being the most effective complexes in the short term on the basis of their chemical structure and stability. The Mn2+ :G7 (1:1 and 1:2) complexes were found to be effective Mn sources for plant nutrition due to their chemical structures providing adequate stability in alkaline solution and their fast-action effect. © 2021 Society of Chemical Industry.


Prevalence of obstructive sleep apnea, associated risk factors, and quality of life among Indian congestive heart failure patients: a cross-sectional survey.
Stable congestive heart failure (CHF) patients frequently suffer from sleep apnea, which worsens the prognosis of heart failure and affects sleep quality of the patient. The present study was undertaken to assess the prevalence of obstructive sleep apnea (OSA) and associated quality of life (QOL) among CHF patients and to ascertain the relationship of OSA with excessive daytime sleepiness and selected demographic, clinical, and anthropometric characteristics. Fifty CHF patients and 50 healthy controls were conveniently recruited at CHF clinic, cardiothoracic and neurosciences center outpatient department, All India Institute of Medical Sciences, New Delhi, India. Participants were interviewed using Epworth Sleepiness Scale, Modified Berlin Questionnaire, Kansas City Cardiomyopathy Questionnaire, and Quebec Sleep Questionnaire. The present study revealed 18% and 8% prevalence of OSA in the CHF and control groups, respectively. The prevalence of OSA was comparable in males and females. Excessive daytime sleepiness was significantly associated with OSA in CHF patients (P = .02). Clinical severity (New York Heart Association class) and duration of illness were not significantly associated with OSA. Increased body mass index and neck circumference were the significant risk factors responsible for OSA. Quality of life of CHF patients was poor, and OSA had a significantly negative impact on the already compromised QOL in CHF patients as well as in individuals with no CHF. Prevalence of OSA is high in CHF patients as well as in the general population, and it has negative impact on the already compromised QOL of CHF patient; therefore, assessment of the risk of OSA and referral for appropriate treatment should be a part of routine nursing clinical workup. Nursing interventions should also be planned to improve sleep quality of CHF patients.


Effects of the Type of Sports Practice on the Executive Functions of Schoolchildren.
There is a close relationship between the development of complex motor skills and executive functions during childhood. This study aimed to analyze the differences in different dimensions of executive functions in children practicing an open-skill sport (handball) and a closed-skill sport (athletics) and controls who did not participate in sports activities after a 12-week intervention period. School-aged male and female subjects (n = 90; mean ± standard deviation = 11.45 ± 0.68 years) participated in a non-randomized controlled study. Data analysis was performed using the STATA V.15 statistical software. The athletics intervention promoted semantic fluency (p = 0.007), whereas handball increased inhibition (p = 0.034). Additionally, physical activity improved in both intervention groups (p = < 0.001), whereas sprint performance improved in the handball group following intervention (p = 0.008), lower body muscular power improved in athletics (p = 0.04), and evidence of improvement in upper body muscular strength was noted in handball (p = 0.037). In turn, an increase in the Physical Activity Questionnaire for older Children score showed an association with the Standard Ten scores of executive functions. In conclusion, compared to controls, both athletics and handball induced meaningful improvements in physical activity and executive functions. However, sport-specific adaptations were noted after athletics (i.e., semantic fluency and lower body muscular power) and handball (i.e., inhibition, sprint, and upper-body muscular strength).


[Mendelian genetics and cancer (author's transl)].
Two hundred different mendelian genes can have a cancerogenic effect in man, but it is difficult to make out between the genetic and the environmental part. Acute lymphoblastic leukemia is an example that the actual cancerogenic factor can be environmental and not genetic. Genetically controlled tumors can result from two successive mutations, the first being in some cases prezygotic. The first genetic accident can be a birth defect or a chromosomic fragility syndrome. The histocompatibility major system can play a role in the frequence and in the evolutive type of some cancers. The most frequent hereditary syndromes which can be associated with cancers are quoted here.


Interaction of the Hsp70 molecular chaperone, DnaK, with its cochaperone DnaJ.
Chaperones of the Hsp70 family bind to unfolded or partially folded polypeptides to facilitate many cellular processes. ATP hydrolysis and substrate binding, the two key molecular activities of this chaperone, are modulated by the cochaperone DnaJ. By using both genetic and biochemical approaches, we provide evidence that DnaJ binds to at least two sites on the Escherichia coli Hsp70 family member DnaK: under the ATPase domain in a cleft between its two subdomains and at or near the pocket of substrate binding. The lower cleft of the ATPase domain is defined as a binding pocket for the J-domain because (i) a DnaK mutation located in this cleft (R167H) is an allele-specific suppressor of the binding defect of the DnaJ mutation, D35N and (ii) alanine substitution of two residues close to R167 in the crystal structure, N170A and T173A, significantly decrease DnaJ binding. A second binding determinant is likely to be in the substrate-binding domain because some DnaK mutations in the vicinity of the substrate-binding pocket are defective in either the affinity (G400D, G539D) or rate (D526N) of both peptide and DnaJ binding to DnaK. Binding of DnaJ may propagate conformational changes to the nearby ATPase catalytic center and substrate-binding sites as well as facilitate communication between these two domains to alter the molecular properties of Hsp70.


Changes in vasopressin use and outcomes in surgical intensive care unit patients with septic shock.
This study compares recent vasopressin use and outcomes to our early practice when vasopressin was introduced for septic shock. Charts of Surgical Intensive Care Unit (SICU) patients receiving vasopressin for septic shock in 2005-2006 (05-06 cohort,) were retrospectively reviewed. Demographics, APACHE II, hemodynamic variables, and vasoactive drug data were compared to a similar 1999-2000 cohort (99-00 cohort). Statistical analysis included general linear model, Chi-square, t-test, and Cox-regression (p < 0.05 considered significant). Thirty-one SICU patients in the 05-06 cohort and twenty patients in the 99-00 cohort met study criteria. Age, weight, gender, intensive care length of stay and vasopressin treatment duration were similar in the two groups. APACHE II (23 +/- 7 versus 34 +/- 9), baseline vasopressin dose (2.2 +/- 1.4 units/hour versus 5.3 +/- 6.7 units/hour), and SICU survival rate (45% versus 15%) significantly changed between the two time periods (p < 0.01). The mean arterial pressure increased significantly from baseline at all measured time points in both groups (p < 0.05). Vasopressin and dopamine doses were significantly lower in the 05-06 cohort versus the 99-00 cohort (p < 0.05). By Cox regression analysis the survival function adjusted for APACHE II was significantly different between groups. Vasopressin is recently used at lower doses and in less severe septic shock. Patients recently treated with vasopressin have a higher SICU survival rate than the survival rate when vasopressin was first introduced for septic shock.


Delusion-like experiences in older people with anxiety disorders.
Little is known about the occurrence of psychotic or quasi-psychotic experiences in older people with anxiety disorders. We used a cross-sectional national probability sample of community-residing individuals to investigate the prevalence and correlates of delusion-like experiences in older people with DSM-IV anxiety disorders. The 2007 Australian National Survey of Mental Health and Well-being (NSMHWB) included 1,905 persons between the ages of 65 and 85 years. Anxiety disorder diagnoses were established using the Composite International Diagnostic Interview (CIDI v3). Participants were asked about three types of delusion-like experiences: thought control or interference, special meaning, and special powers. We used multivariate logistic regression to examine the relationship between a 12-month history of any anxiety disorder and the presence of these delusion-like experiences, adjusting for several potential confounders. Eighty-two of 1,905 (4.3%) older people met criteria for an anxiety disorder over the previous 12 months. Of these, six reported delusion-like experiences, whereas the prevalence of these experiences among older people without anxiety disorder was 26/1,822 (7.3% vs. 1.4%; χ(2) = 16.5; p = 0.000). In a logistic regression model, male gender (OR 0.38; p = 0.019), separated marital status (OR 4.86; p = 0.017), and the presence of anxiety disorder (OR 5.33; p = 0.001) were independently associated with delusion-like experiences, whereas MMSE (Mini-Mental State Examination) score, general medical conditions and affective disorder were not. In this cross-sectional study, self-reported delusion-like experiences occurred at increased prevalence among community-residing older persons with anxiety disorder. More work is needed to clarify the nature and significance of these findings.


Association of the time that elapsed from last vaccination with protective effectiveness against foot-and-mouth disease in small ruminants.
Routine and emergency vaccination of small ruminants against foot-and-mouth disease (FMD) is mandatory in many endemic countries, yet data on the field effectiveness of the vaccines used is scarce. We conducted an investigation of a serotype O FMD outbreak that took place in a sheep and goat pen, and estimated the effectiveness of various routine vaccination statuses. We also evaluated the protection provided by colostrum administration and emergency vaccination. Animals which were routinely vaccinated twice were not clinically affected while disease incidence was observed among animals routinely vaccinated only once (p = 0.004 according to a two-sided Fisher's exact test). In groups vaccinated only once, there was a significant association between the average time that elapsed since last vaccination and the disease incidence (n = 5; Spearman correlation coefficient: rs = 1.0, p < 0.01). In addition, non-vaccinated lambs fed colostrum from dams vaccinated more than 2 months before parturition had a mortality rate of 33%. Administration of emergency vaccination 2 days after the occurrence of the index case was the probable reason for the rapid blocking of the FMD spread within 6 days from its onset in the pen.


Exploring the Cervical Cancer Screening Experiences of Black Lesbian, Bisexual, and Queer Women: The Role of Patient-Provider Communication.
Few studies have focused on the health and health care of U.S. black lesbian, bisexual, and queer (LBQ) women. To understand the facilitators of and barriers to cervical cancer screening in this population, focus group discussions were conducted in Boston and Cambridge, Massachusetts between November and December 2012. Using purposive sampling methods, the authors enrolled 18 black LBQ women who participated in one of four focus groups. Using thematic analysis, patient-provider communication was identified, which consisted of four sub-themes--health care provider communication style and demeanor; heteronormative provider assumptions; heterosexism, racism, and classism; and provider professional and sociodemographic background--as the most salient theme. Participants reported fears and experiences of multiple forms of discrimination and preferred receiving care from providers who were knowledgeable about same-sex sexual health and shared their life experiences at the intersection of gender, race/ethnicity, and sexual orientation. The cervical cancer screening experiences of black LBQ women would be improved by training all health care providers in same-sex sexual health, offering opportunities for clinicians to learn about the effects of various forms of discrimination on women's health care, and increasing the presence of LBQ women of color in health care settings.


Feasibility and effectiveness of daily temperature screening to detect COVID-19 in a prospective cohort at a large public university.
Many persons with active SARS-CoV-2 infection experience mild or no symptoms, presenting barriers to COVID-19 prevention. Regular temperature screening is nonetheless used in some settings, including university campuses, to reduce transmission potential. We evaluated the potential impact of this strategy using a prospective university-affiliated cohort. Between June and August 2020, 2912 participants were enrolled and tested for SARS-CoV-2 by PCR at least once (median: 3, range: 1-9). Participants reported temperature and symptoms daily via electronic survey using a previously owned or study-provided thermometer. We assessed feasibility and acceptability of daily temperature monitoring, calculated sensitivity and specificity of various fever-based strategies for restricting campus access to reduce transmission, and estimated the association between measured temperature and SARS-CoV-2 test positivity using a longitudinal binomial mixed model. Most participants (70.2%) did not initially have a thermometer for taking their temperature daily. Across 5481 total person months, the average daily completion rate of temperature values was 61.6% (median: 67.6%, IQR: 41.8-86.2%). Sensitivity for SARS-CoV-2 ranged from 0% (95% CI 0-9.7%) to 40.5% (95% CI 25.6-56.7%) across all strategies for self-report of possible COVID-19 symptoms on day of specimen collection, with corresponding specificity of 99.9% (95% CI 99.8-100%) to 95.3% (95% CI 94.7-95.9%). An increase of 0.1 °F in individual mean body temperature on the same day as specimen collection was associated with 1.11 increased odds of SARS-CoV-2 positivity (95% CI 1.06-1.17). Our study is the first, to our knowledge, that examines the feasibility, acceptability, and effectiveness of daily temperature screening in a prospective cohort during an infectious disease outbreak, and the only study to assess these strategies in a university population. Daily temperature monitoring was feasible and acceptable; however, the majority of potentially infectious individuals were not detected by temperature monitoring, suggesting that temperature screening is insufficient as a primary means of detection to reduce transmission of SARS-CoV-2.


Mutations of the caenorhabditis elegans brain-specific inorganic phosphate transporter eat-4 affect habituation of the tap-withdrawal response without affecting the response itself.
The studies reported here were designed to investigate the role of the mutation eat-4 in the response to tap and in habituation in the nematode Caenorhabditis elegans. In C. elegans eat-4 has been found to affect a number of glutamatergic pathways. It has been hypothesized to positively regulate glutaminase activity and therefore glutamatergic neurotransmission. In the eat-4(ky5) loss-of-function worms, there is presumably insufficient glutamate available for sustained transmission. In the experiments reported here eat-4 worms showed no differences from wild-type in the magnitude of response to a single tap, indicating that the neural circuit underlying the response was intact and functional in the mutant worms. However, when eat-4 worms were given repeated taps the resulting habituation was different from that seen in wild-type worms: eat-4 worms habituate more rapidly and recover more slowly than wild-type worms at all interstimulus intervals tested. In addition, eat-4 worms do not show dishabituation. The same transgene rescues pharyngeal activity defects and both the habituation and dishabituation deficits seen in the eat-4 worms. Our results suggest that neurotransmitter regulation plays a role in habituation and may play a role in dishabituation.


Influences of mesoporous magnesium silicate on the hydrophilicity, degradability, mineralization and primary cell response to a wheat protein based biocomposite.
A novel bioactive composite based on wheat protein (WP) and mesoporous magnesium silicate (m-MS) with a high specific surface area is presented in this study for potential bone tissue regeneration. Wheat protein (WP) is a type of a biodegradable natural polymer material. The m-MS was prepared by the sol-gel technique, which was incorporated into WP to fabricate m-MS/WP composites. The increasing amount of m-MS improved the surface hydrophilicity of m-MS/WP composites. The results showed that the degradation ratio of the m-MS/WP composites increased with an increase in the m-MS content after it was soaked in a Tris-HCl solution for 12 weeks. Moreover, the m-MS/WP composites with 40 wt% m-MS content (WP40) were able to maintain a suitable pH value over a prolonged soaking time, which might be dependent on the content of the m-MS. The WP40 showed a good apatite formation ability after it was soaked in simulated body fluid (SBF) for 7 days, indicating good bioactivity. Moreover, the WP40 with cytocompatibility stimulated the attachment, proliferation and differentiation of MC3T3-E1 osteoblast cells. Briefly, the results indicated that WP40 had good bioactivity, degradability, cytocompatibility and osteogenesis and might be a new biomaterial for bone regeneration.


Palladium(0)-Catalyzed Benzylic C(sp3)-H Functionalization for the Concise Synthesis of Heterocycles and Its Applications.
C-H functionalization reactions involve the activation of otherwise unreactive C-H bonds, and represent atom economical methods for the direct transformation of simple substrates to complex molecules. While transition metal-catalyzed C(sp2)-H functionalization reactions are regularly used in synthesis, C(sp3)-H functionalization is rarely applied to the synthesis of complex natural products because of the difficulties associated with controlling selectivity. With this in mind, we focused on the development of new palladium (Pd)(0)-catalyzed C(sp3)-H functionalization reactions for the synthesis of complex molecules, resulting in several new methods capable of solving these problems. We initially developed a concise synthetic method for the facile construction of oxindoles and spirooxindoles via a Pd-catalyzed benzylic C(sp3)-H functionalization reaction. This method was subsequently extended to the synthesis of various heterocycles, including 2-arylindoles, benzocarbazole, indolocarbazole, indoloquinazolinone, and indoloquinazolinedione, as well as the total synthesis of several pyrrolophenanthridine alkaloids without the need for any protecting groups. This method was also successfully applied to the synthesis of the right-hand fragment of benzohopane from tetrahydro-2H-fluorene, which was constructed by a Pd-catalyzed benzylic C(sp3)-H functionalization. In this review, we provide a detailed discussion of our most recent investigations pertaining to Pd(0)-catalyzed benzylic C(sp3)-H functionalization.


Unilateral antegrade cerebral perfusion through the right axillary artery provides uniform flow distribution to both hemispheres of the brain: A magnetic resonance and histopathological study in pigs.
Bilateral antegrade cerebral perfusion (ACP) has decreased in popularity over the past decade because of its complexity and the risk of cerebral embolism. We used magnetic resonance (MR) perfusion imaging to assess flow distribution in both hemispheres of the brain during unilateral ACP through the right carotid artery via a cannula placed in the right axillary artery in conjunction with hypothermic circulatory arrest. Twelve pigs were randomly exposed to 120 minutes of either bilateral ACP through both carotid arteries (n=6) or unilateral ACP through the right axillary artery (n=6) at pressures of 60 to 65 mm Hg at 15 degrees C, followed by 60 minutes of cardiopulmonary bypass at 37 degrees C. MR perfusion images were acquired every 30 minutes before, during, and after ACP. The brain was perfusion fixed for histopathology. During initial normothermic cardiopulmonary bypass, MR perfusion imaging showed a uniform distribution of flow in the brain. In both the bilateral and unilateral ACP groups, the same pattern was maintained, with an increase in regional cerebral blood volume during ACP and reperfusion. The changes in regional cerebral blood volume and mean transit time were similar in both hemispheres during and after unilateral ACP. No difference was observed between the 2 groups. Histopathology showed normal morphology in all regions of the brain in both groups. Both bilateral ACP and unilateral ACP provide uniform blood distribution to both hemispheres of the brain and preserve normal morphology of the neurons after prolonged hypothermic circulatory arrest.


Identifying determinants of quality of life of children with cancer and childhood cancer survivors: a systematic review.
This paper describes a systematic review conducted to identify factors that have been investigated as explanations of variability in the quality of life of children with cancer and childhood cancer survivors. Our purpose was to build an evidence base that could be used to guide and direct future research. MEDLINE, CINAHL, EMBASE, PsycINFO, Cancerlit, and Sociological Abstracts were searched from the inception of each database to June 15, 2009 using the following search terms: "quality of life," "health-related quality of life," "quality adjusted life years," "health status," "functional status," "well-being," or "patient-reported outcome." Sample characteristics and information about the relationship between a quality of life domain or total scale score and at least one factor (e.g., child gender or age, coping skills, family income) were extracted from eligible studies. Nine cancer-specific and nine generic QOL questionnaires were used in 58 publications described 239 factors (50 unique factors). The large number of cancer, treatment, child, and family variables considered indicates that extensive research activity has occurred. However, most of the variables identified were examined in only a few studies and most represent medical and treatment variables with less research attention paid to child and family variables. Our study has compiled evidence about determinants of QOL for children with cancer and childhood cancer survivors from the existing literature. Future research can build on this evidence base to expand the range of factors studied as most research to date has focused on medical and treatment factors.


Stress Watch: The Use of Heart Rate and Heart Rate Variability to Detect Stress: A Pilot Study Using Smart Watch Wearables.
Stress is an inherent part of the normal human experience. Although, for the most part, this stress response is advantageous, chronic, heightened, or inappropriate stress responses can have deleterious effects on the human body. It has been suggested that individuals who experience repeated or prolonged stress exhibit blunted biological stress responses when compared to the general population. Thus, when assessing whether a ubiquitous stress response exists, it is important to stratify based on resting levels in the absence of stress. Research has shown that stress that causes symptomatic responses requires early intervention in order to mitigate possible associated mental health decline and personal risks. Given this, real-time monitoring of stress may provide immediate biofeedback to the individual and allow for early self-intervention. This study aimed to determine if the change in heart rate variability could predict, in two different cohorts, the quality of response to acute stress when exposed to an acute stressor and, in turn, contribute to the development of a physiological algorithm for stress which could be utilized in future smartwatch technologies. This study also aimed to assess whether baseline stress levels may affect the changes seen in heart rate variability at baseline and following stress tasks. A total of 30 student doctor participants and 30 participants from the general population were recruited for the study. The Trier Stress Test was utilized to induce stress, with resting and stress phase ECGs recorded, as well as inter-second heart rate (recorded using a FitBit). Although the present study failed to identify ubiquitous patterns of HRV and HR changes during stress, it did identify novel changes in these parameters between resting and stress states. This study has shown that the utilization of HRV as a measure of stress should be calculated with consideration of resting (baseline) anxiety and stress states in order to ensure an accurate measure of the effects of additive acute stress.


Serum and urinary biomarker signatures for rapid preclinical in vivo assessment of CDK inhibition as a therapeutic approach for PKD.
Recent advances in understanding the molecular pathogenesis of polycystic kidney diseases (PKD) are being translated into promising treatments. Currently, a response to therapy in preclinical animal models of PKD can only be evaluated after several weeks of treatment. The availability of biomarkers for rapid efficacy assessment would greatly facilitate the drug development process. Here we applied SELDI-TOF technology to establish serum and urinary biomarker signatures associated with a rapid therapeutic response to cyclin dependent kinase (CDK) inhibitor roscovitine in the jck mouse model of PKD. A set of 74 serum and 56 urinary markers was identified in the group receiving chronic treatment over 5 weeks. This set was further screened for early efficacy biomarkers in acutely (3-5 days) treated animals with mild (26 days of age) and advanced disease (50 days of age). A third group with intermediate disease (33 days of age) received a single injection to monitor rapid changes in protein profiles within 4, 24 or 48 hours after drug administration. Multifactorial comparative analysis of the acutely treated groups identified a set of 20 urinary and 21 serum efficacy biomarkers. This biomarker signature provides a necessary tool for further assessment of CDK inhibitors as therapeutic agents for PKD.


Two adjacent NAC transcription factors regulate fruit maturity date and flavor in peach.
Although maturity date (MD) is an essential factor affecting fresh fruit marketing and has a pleiotropic effect on fruit taste qualities, the underlying mechanisms remain largely unclear. In this study, we functionally characterized two adjacent NAM-ATAF1/2-CUC2 (NAC) transcription factors (TFs), PpNAC1 and PpNAC5, both of which were associated with fruit MD in peach. PpNAC1 and PpNAC5 were found capable of activating transcription of genes associated with cell elongation, cell wall degradation and ethylene biosynthesis, suggesting their regulatory roles in fruit enlargement and ripening. Furthermore, PpNAC1 and PpNAC5 had pleiotropic effects on fruit taste due to their ability to activate transcription of genes for sugar accumulation and organic acid degradation. Interestingly, both PpNAC1 and PpNAC5 orthologues were found in fruit-producing angiosperms and adjacently arranged in all 91 tested dicots but absent in fruitless gymnosperms, suggesting their important roles in fruit development. Our results provide insight into the regulatory roles of NAC TFs in MD and fruit taste.


Antioxidant Mechanisms of Echinatin and Licochalcone A.
Echinatin and its 1,1-dimethyl-2-propenyl derivative licochalcone A are two chalcones found in the Chinese herbal medicine Gancao. First, their antioxidant mechanisms were investigated using four sets of colorimetric measurements in this study. Three sets were performed in aqueous solution, namely Cu2+-reduction, Fe3+-reduction, and 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide radical (PTIO•)-scavenging measurements, while 1,1-diphenyl-2-picrylhydrazyl radical (DPPH•)-scavenging colorimetric measurements were conducted in methanol solution. The four sets of measurements showed that the radical-scavenging (or metal-reduction) percentages for both echinatin and licochalcone A increased dose-dependently. However, echinatin always gave higher IC50 values than licochalcone A. Further, each product of the reactions of the chalcones with DPPH• was determined using electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS/MS). The UPLC-ESI-Q-TOF-MS/MS determination for echinatin yielded several echinatin⁻DPPH adduct peaks (m/z 662, 226, and 196) and dimeric echinatin peaks (m/z 538, 417, and 297). Similarly, that for licochalcone A yielded licochalcone A-DPPH adduct peaks (m/z 730, 226, and 196) and dimeric licochalcone A peaks (m/z 674 and 553). Finally, the above experimental data were analyzed using mass spectrometry data analysis techniques, resonance theory, and ionization constant calculations. It was concluded that, (i) in aqueous solution, both echinatin and licochalcone A may undergo an electron transfer (ET) and a proton transfer (PT) to cause the antioxidant action. In addition, (ii) in alcoholic solution, hydrogen atom transfer (HAT) antioxidant mechanisms may also occur for both. HAT may preferably occur at the 4-OH, rather than the 4'-OH. Accordingly, the oxygen at the 4-position participates in radical adduct formation (RAF). Lastly, (iii) the 1,1-dimethyl-2-propenyl substituent improves the antioxidant action in both aqueous and alcoholic solutions.


High-sensitivity C reactive protein as a predictor of inhospital mortality in patients with cardiovascular disease at an emergency department: a retrospective cohort study.
We investigated whether serum high-sensitivity C reactive protein (hs-CRP) levels measured in an emergency department (ED) are associated with inhospital mortality in patients with cardiovascular disease (CVD). A retrospective cohort study. ED of a teaching hospital in Japan. 12 211 patients with CVD aged ≥18 years who presented to the ED by an ambulance between 1 February 2006 and 30 September 2014 were evaluated. Inhospital mortality. 1156 patients had died. The inhospital mortality increased significantly with the hs-CRP levels (<3.0 mg/L: 7.0%, 95% CI 6.4 to 7.6; 3.1-5.4 mg/L: 9.6%, 95% CI 7.9 to 11.3: 5.5-11.5 mg/L: 11.2%, 95% CI 9.4 to 13.0; 11.6-33.2 mg/L: 12.3%, 95% CI 10.5 to 14.1 and ≥33.3 mg/L: 19.9%, 95% CI 17.6 to 22.2). The age-adjusted and sex-adjusted HR for total mortality was increased significantly in the three ≥5.5 mg/L groups compared with the <3.0 mg/L group (5.5-11.5 mg/L: HR=1.32, 95% CI 1.09 to 1.60, p=0.005; 11.6-33.2 mg/L: HR=1.38, 95% CI 1.14 to 1.65, p=0.001 and ≥33.3 mg/L: HR=2.15, 95% CI 1.84 to 2.51, p<0.001). Similar findings were observed for the CVD subtypes of acute myocardial infarction, heart failure, cerebral infarction and intracerebral haemorrhage. This association remained unchanged even after adjustment for age, sex and white cell count and withstood Bonferroni adjustment for multiple testing. When the causes of death were divided into primary CVD and non-CVD deaths, the association between initial hs-CRP levels and mortality remained significant, but the influence of hs-CRP levels was greater in non-CVD deaths than CVD deaths. The percentage of non-CVD deaths increased with hs-CRP levels; among the patients with hs-CRP levels ≥33.3 mg/L, non-CVD deaths accounted for 37.5% of total deaths. Our findings suggest that increased hs-CRP is a significant risk factor for inhospital mortality among patients with CVD in an ED. Particular attention should be given to our finding that non-CVD death is a major cause of death among patients with CVD with higher hs-CRP levels.


"Candidatus Liberibacter solanacearum" Associated With the Psyllid, Bactericera maculipennis (Hemiptera: Triozidae).
The psyllid Bactericera maculipennis (Crawford) (Hemiptera: Triozidae) often cohabits field bindweed (Convolvulus arvensis, Solanales: Convolvulaceae) and other plants with the congeneric psyllid, Bactericera cockerelli (Šulc), in the Pacific Northwestern United States. Bactericera cockerelli is a vector of "Candidatus Liberibacter solanacearum," the pathogen associated with zebra chip disease of potato (Solanales: Solanaceae). Because B. maculipennis and B. cockerelli both naturally occur on certain plants, we surveyed B. maculipennis adults collected from Washington and Idaho for presence of "Ca. L. solanacearum" to determine whether this psyllid also harbors this pathogen. Liberibacter was present in 30% of field-collected B. maculipennis and in 100% of colony-reared psyllids. Sequences of 16S rDNA and microsatellite markers revealed that "Ca. L. solanacearum" from B. maculipennis was closely related to Liberibacter haplotype B from B. cockerelli. Results of laboratory assays demonstrated that Liberibacter can be transmitted between B. cockerelli and B. maculipennis on plants within the Convolvulaceae. Potato plants challenged with Liberibacter-infected B. maculipennis did not become infected, apparently because potato is not a suitable host for the psyllid. We therefore conclude that B. maculipennis is not a direct threat to potato production, despite its association with Liberibacter. We are the first to report that "Ca. L. solanacearum" is associated with a psyllid other than B. cockerelli in North America. Results of our study demonstrate the importance of understanding the complete ecology of psyllids-including interactions with other psyllids on non-crop hosts-in predicting what crops or regions are potentially susceptible to the spread of Liberibacter.


Cold agglutinin activity in 2 dogs.
A 5-year-old neutered male Mastiff and an 8-year-old spayed female Labrador Retriever were presented to the University of Minnesota Veterinary Medical Center. The Mastiff was presented for evaluation of lameness and pyoderma one month prior in Missouri, where he tested positive for Ehrlichia canis by serum ELISA test, treated with doxycycline. PCR for Ehrlichia sp, Anaplasma sp, Babesia sp, and Bartonella sp, and PCR for antigen receptor rearrangement were negative, serum protein electrophoresis (SPE) revealed polyclonal gammopathy, and mildly reactive lymphoid cells were seen cytologically. The Labrador presented with a proliferative rostral mandibular gingival mass and lipomas for further presurgical evaluation of cold agglutinin activity documented by a commercial laboratory 2 years earlier prior to removal of a grade II mast cell tumor. This dog had a negative SNAP4Dx, normal SPE, and persistently increased serum ALP activity and polyuria/polydipsia suggestive for hyperadrenocorticism. Both dogs had markedly agglutinated RBC in the EDTA samples that dispersed with warming, and normal plasma color. Cold agglutinin activity was demonstrated by direct saline agglutination testing using whole blood and washed erythrocytes demonstrating agglutination at 30°C, 25°C, 15°C, and 4°C, but not at 37°C. CBC results (ADVIA 2120i) from the Mastiff revealed no significant differences in the RBC results obtained at room temperature (RT) and at 37°C; however, the RT run demonstrated negative bias in neutrophil and platelet concentrations attributed to rapid RBC settling. This uncommon hematologic condition may cause artifacts on the automated leukogram and platelet count, and may be subclinical for long periods.


Prospective randomized study of individual and group psychotherapy versus controls in recipients of renal transplants.
Recipients of kidney transplant have been shown to develop emotional problems. These have been associated with medical noncompliance, compromised quality of life, and difficulty integrating the newly acquired transplant into their sense of self. In general, group psychotherapy has been shown to be more cost effective than individual therapy. We have compared the efficacy of two modalities of therapy in recipients of kidney transplants with control patients who did not receive therapy. Recipients of first cadaver kidney transplants were randomized into two groups to receive a 12-week course of group or individual psychotherapy. The control arm of the study was composed of 37 consecutive patients who had received a first cadaver kidney. Recipients of live kidney transplants, and patients who received more than one kidney transplant, were excluded because these patients have different emotional issues. The Beck Depression Inventory (BDI) was used as a measure of change in emotional state, pretherapy, at 3, 6, 9, and 12 months. A higher score on BDI was suggestive of psychologic dysfunction. We recruited 89 recipients of first cadaver kidney transplants into the study. They were randomly allocated into the two study groups, 49 for individual therapy, and 40 for group therapy. Of these, 82 patients completed 12 weeks of therapy (45 patients from the individual treatment arm, and 37 from the group therapy arm). Fifty-five patients completed one-year follow-up (33 in individual therapy, and 32 in the group therapy). The mean score was 26.3 +/- 7.9 before and 18.9 +/- 9.0 after therapy in the individual treatment group (P= 0.001). This was in comparison with a mean score of 30.2 +/- 3.8 before and 26.0 +/- 4.2 after therapy for the group therapy arm (P= 0.01). Improvement appeared to be more significant in the individual therapy compared with group therapy (P= 0.01). Lowering of scores was progressive and sustained (P= 0.01). In the control arm, mean score was 9.4 +/- 5.4 before and 20.5 +/- 5.5 at the end of the first year (P= 0.005), suggesting a significant worsening of BDI scores. Multivariate analysis of age, gender, employment status, duration of dialysis, etiology of kidney failure, diabetes mellitus, and psychotherapy received at any time before transplantation did not affect results. We conclude that both individual and group psychotherapy were beneficial to our patients; however, individual therapy was found to result in lower BDI scores versus group therapy at the end of treatment period.


Effects of 360-degree pedicle torsion on island skin flaps: experimental study in rats.
This study was carried out to observe the isolated effects of pedicle torsion on island skin flaps, without further damaging the pedicle. Twelve adult male Sprague-Dawley rats, weighting 240 to 300 gr, were used, and hexagonal flaps with edges measuring 1.5 cm and pedicles measuring 1 cm in length were raised in the inguinal region. The animals were divided into two groups. In Group A, flaps were re-sutured to the donor beds without any rotation. In Group B, flaps were rotated 360 degrees, applying the same degree of torsion to their pedicles before re-suturing. After 7 days, the percentage of surviving skin areas of the flaps was determined by planimetry, and transverse sections of the flaps and pedicles were taken and evaluated in terms of signs of arterial or venous insufficiency. Statistically significant differences between the groups were determined by analyses using the multiple comparisons test. Pedicle torsion in Group B did not affect flap viability, both macroscopically and microscopically. The presented study shows that 360-degree torsion applied to the pedicle of the flap in this model had no effect on flap viability.


Dietary Cerebroside from Sea Cucumber (Stichopus japonicus): Absorption and Effects on Skin Barrier and Cecal Short-Chain Fatty Acids.
Sphingolipids from marine sources have attracted more attention recently because of their distinctive structures and expected functions. In this study, the content and components of cerebroside from sea cucumber Stichopus japonicus were analyzed. The absorption of cerebroside from S. japonicus was investigated with an in vivo lipid absorption assay. The result revealed that S. japonicus is a rich source of cerebroside that contained considerable amounts of odd carbon chain sphingoid bases. The cumulative recoveries of d17:1- and d19:2-containing cerebrosides were 0.31 ± 0.16 and 0.32 ± 0.10%, respectively, for 24 h after administration. To the best of the authors' knowledge, this is the first work that shows sphingolipids from a marine source could be absorbed in vivo and incorporated into ceramides. In addition, dietary supplementation with sea cucumber cerebroside to hairless mouse improved the skin barrier function and increased short-chain fatty acids in cecal contents, which have shown beneficial effects on the host.


Gastric carcinoids of ECL cells. Pathological and clinical analysis of eight cases.
Clinical, histological, histochemical and ultrastructural characteristics of eight cases of carcinoid tumors of the non-antral portion of the stomach are presented. Four cases with multiple polypoid lesions are accompanied by an increased level of gastrin. A normal level of gastrin was present in the other four cases with isolated tumor and a normal component of endocrine cells in the uninvolved mucosa. In the first group with multiple lesions, the histological and histochemical analysis of the endocrine cells revealed a wide range of appearances: a) "simple hyperplasia", b) "nodular hyperplasia", and c) carcinoid tumor. These aspects suggested a different pathogenesis for the carcinoid tumors of the non-antral portion of the stomach with possible therapeutical implications.


NF-κB Inhibitor Parthenolide Promotes Renal Tubules Albumin Uptake in Type 2 Diabetic Nephropathy.
Objective Injured tubular reabsorption is highlighted as one of the causes of increased albuminuria in the early stage of diabetic nephropathy; however, the underlying mechanism has not been fully elucidated. In this study, we aimed to explore whether reducing inflammation and remodeling the insulin signaling pathway could improve albumin uptake of renal tubules. Methods 8-week-old male db/db mice (n=8), a type 2 diabetic nephropathy model, administered with nuclear factor kappa-B (NF-κB) inhibitor parthenolide (PTN, 1 mg/kg) intraperitoneally every other day for 8 weeks, were as the treatment group. Meanwhile, the age-matched male db/m mice (n=5) and db/db mice (n=8) were treated with saline as the control group and type 2 diabetic nephropathy group. When the mice were sacrificed, blood and urine were collected to examine homeostasis model assessment of insulin resistance (HOMA-IR) and urine albumin creatinine ratio, and kidney samples were used to analyze histopathologic changes with periodic acid-Schiff (PAS) staining, NF-κB p65, phosphorylation of AKT (p-AKT), amnionless and cubilin expressions with immunohistochemistry as well as western blot, and the albumin uptake of renal tubules by using immunofluorescence. In addition, HKC cells were divided into the insulin group treated with insulin alone, the TNF-α group treated with insulin and tumor necrosis factor (TNF-α), and the TNF-α+PTN group exposed to PTN, insulin and TNF-α. The levels of albumin uptake and expression levels of NF-κB p65, p-IRS-1/IRS-1, p-AKT/AKT, amnionless and cubilin in HKC cells were measured. Results Compared with the db/db group, the db/db+PTN group demonstrated decreased levels of HOMA-IR (36.83±14.09 vs. 31.07±28.05) and urine albumin creatinine ratio (190.3±7.3 vs. 143.0±97.6 mg/mmol); however, the differences were not statistically significant (P>0.05). Periodic acid-Schiff staining showed PTN could alleviate the glomerular hypertrophy and reduce the matrix in mesangial areas of db/db mice. The renal expression of NF-κB p65 was increased and p-AKT (s473) decreased in the db/db group compared with the db/m group (P<0.05). PTN significantly reduced the renal expression of NF-κB p65 and ameliorated the decline of p-AKT (s473) compared with the db/db group (P<0.05). Compared with the db/m group, the expression of amnionless and cubilin decreased and albumin uptake in tubules were reduced in the db/db group (P<0.05), and PTN could significantly increase the expression of cubilin (P<0.05), and improve albumin uptake in tubules. Insulin promoted albumin uptake and the expression of amnionless and cubilin in HKC cells (P<0.05). TNF-α stimulated the expression of NF-κB p65, increased p-IRS-1 (s307) and reduced p-AKT (s473) in HKC cells (P<0.05). In the TNF-α+PTN group, the expression of NF-κB p65 declined and p-IRS-1 (s307) and p-AKT (s473) were restored, compared with the TNF-α group (P<0.05). The expression of amnionless and cubilin decreased in the TNF-α group (P<0.05), and PTN could significantly increase the expression of cubilin (P<0.05). Conclusions Inflammation caused damage to insulin signaling, which reduced amnionless-cubilin expression and albumin uptake. PTN could reduce inflammation and remodel the impaired insulin signaling pathway, which promoted the expression of cubilin and albumin uptake. Our study can shed light on the role of inflammation in the reduction of albumin uptake of renal tubules in type 2 diabetic nephropathy.


MCHP (Monte Carlo + Human Phantom): Platform to facilitate teaching nuclear radiation physics.
Some concepts in nuclear radiation physics are abstract and intellectually demanding. In the present paper, an "MCHP platform" (MCHP was an acronym for Monte Carlo simulations + Human Phantoms) was proposed to provide assistance to the students through visualization. The platform involved Monte Carlo simulations of interactions between ionizing radiations and the Oak Ridge National Laboratory (ORNL) adult male human phantom. As an example to demonstrate the benefits of the proposed MCHP platform, the present paper investigated the variation of the absorbed photon dose per photon from a 137Cs source in three selected organs, namely, brain, spine and thyroid of an adult male for concrete and lead shields with varying thicknesses. The results were interesting but not readily comprehensible without direct visualization. Graphical visualization snapshots as well as video clips of real time interactions between the photons and the human phantom were presented for the involved cases, and the results were explained with the help of such snapshots and video clips. It is envisaged that, if the platform is found useful and effective by the readers, the readers can also propose examples to be gradually added onto this platform in future, with the ultimate goal of enhancing students' understanding and learning the concepts in an undergraduate nuclear radiation physics course or a related course.


Effect of evolution of the C-terminal region on chaperone activity of Hsp70.
Dynamic interdomain interactions within the Hsp70 protein is the basis for the allosteric and functional properties of Hsp70s. While Hsp70s are generally conserved in terms of structure, allosteric behavior, and some overlapping functions, Hsp70s also contain variable sequence regions which are related to distinct functions. In the Hsp70 sequence, the part with the greatest sequence variation is the C-terminal α-helical lid subdomain of substrate-binding domain (SBDα) together with the intrinsically disordered region. Dynamic interactions between the SBDα and β-sandwich substrate-binding subdomain (SBDβ) contribute to the chaperone functions of Hsp70s by tuning kinetics of substrate binding. To investigate how the C-terminal region of Hsp70 has evolved from prokaryotic to eukaryotic organisms, we tested whether this region can be exchanged among different Hsp70 members to support basic chaperone functions. We found that this region from eukaryotic Hsp70 members cannot substitute for the same region in Escherichia coli DnaK to facilitate normal chaperone activity of DnaK. In contrast, this region from E. coli DnaK and Saccharomyces cerevisiae Hsp70 (Ssa1 and Ssa4) can partially support some roles of human stress inducible Hsp70 (hHsp70) and human cognate Hsp70 (hHsc70). Our results indicate that the C-terminal region from eukaryotic Hsp70 members cannot properly support SBDα-SBDβ interactions in DnaK, but this region from DnaK/Ssa1/Ssa4 can still form some SBDα-SBDβ interactions in hHsp70 or hHsc70, which suggests that the mode for SBDα-SBDβ interactions is different in prokaryotic and eukaryotic Hsp70 members. This study provides new insight in the divergency among different Hsp70 homologs and the evolution of Hsp70s.


Correlations of low-field NMR and variable-field NMR parameters with osteoarthritis in human articular cartilage under load.
NMR experiments carried out at magnetic fields below 1 T provide new relaxation parameters unavailable with conventional clinical scanners. Contrast of T1 generally becomes larger towards low fields, as slow molecular reorientation processes dominate relaxation at the corresponding Larmor frequencies. This advantage has to be considered in the context of lower sensitivity and frequently reduced spatial resolution. The layered structure of cartilage is one example where a particularly strong variation of T1 across the tissue occurs, being affected by degenerative diseases such as osteoarthritis (OA). Furthermore, the presence of 1 H-14 N cross-relaxation, leading to so-called quadrupolar dips in the 1 H relaxation time dispersion, provide insight into the concentration and mobility of proteoglycans and collagen in cartilage, both being affected by OA. In this study, low-field imaging and variable-field NMR relaxometry were combined for the first time for tissue samples, employing unidirectional load to probe the mechanical properties. 20 human knee cartilage samples were placed in a compression cell, and studied by determining relaxation profiles without and with applied pressure (0.6 MPa) at 50 μm in-plane resolution, and comparing with volume-averaged T1 dispersion. Samples were subsequently stored in formalin, prepared for histology and graded according to the Mankin score system. Quadrupolar dips and thickness change under load showed the strongest correlation with Mankin grade. Average T1 and change of maximum T1 under load, as well as its position, correlate with thickness and thickness change. Furthermore, T1 (ω) above 25 mT was found to correlate with thickness change. While volume-averaged T1 is not a suitable indicator for OA, its change due to mechanical load and its extreme values are suggested as biomarkers available in low-field MRI systems. The shape of the dispersion T1 (ω) represents a promising access to understanding and quantifying molecular dynamics in tissue, pointing toward future in vivo tissue studies.


Suggested role for G4 DNA in recombinational switching at the antigenic variation locus of the Lyme disease spirochete.
Antigenic variation through targeted DNA rearrangements provides a powerful diversity generating mechanism that allows a variety of pathogens to stay one step ahead of acquired immunity in their hosts. The Lyme disease spirochete encodes such a system that is required for persistent infection. The vls locus, carried on a 29 kb linear plasmid (lp28-1) in the type strain B31, carries 15 silent cassettes from which information is unidirectionally transferred into the expression locus, vlsE. Recent studies have surprisingly shown that, with the exception of the RuvAB branch migrase, no other known recombination/repair proteins appear to play a role in the recombinational switching process. In the work presented here we show that G4 DNA can be formed by sequences within the B31 vlsE locus, prompting us to investigate the presence of potential G4-forming DNA throughout the vls locus of several Lyme spirochete strains and species. We found that runs of G, three nucleotides and longer occur at a very high density, with a greater than 100-fold strand-specific distribution in the vls locus of three B. burgdorferi strains as well as in B. afzelii and B. garinii, in spite of the bias for the use of A-T rich codons in Borrelia species. Our findings suggest the possibility that G4 DNA may be a mediator of recombinational switching at the vlsE locus in the Lyme spirochetes.


Complete versus anterior two-thirds corpus callosotomy in children: analysis of outcome.
The goal of this study was to evaluate the efficacy of anterior versus complete sectioning of the corpus callosum in children suffering from medically refractory epilepsy. The authors report seizure outcome in patients who underwent anterior two-thirds or complete corpus callosotomy (CC) during the period 1995-2008 at St. Louis Children's Hospital. The medical records of 27 children and adolescents with a minimum follow-up of 6 months were retrospectively evaluated with respect to seizure status, anticonvulsant outcomes, and subjective results. Preoperatively, patients suffered from a variety of seizure types that occurred daily, weekly, or episodically. The male/female ratio was 19:8, and patients ranged in age between 3 and 19 years (mean 9.93 years). Seizure outcome, parental assessment of daily function, and changes in the number of prescribed antiepileptic drugs were all assessed. Fifteen patients underwent an initial anterior two-thirds CC, and 12 underwent a complete CC. Of the 15 patients who underwent an anterior CC, 7 went on to receive a posterior CC. Seizure control was superior in children undergoing a complete CC (91%, Class I-III) versus an anterior two-thirds CC (75%, Class I-III). Seizure types most affected by CC included atonic, myoclonic, and absence. The number of postoperative antiepileptic drugs did not significantly change following CC in either the anterior only or complete groups. One patient experienced a transient disconnection syndrome that resolved within 4 weeks, and 4 patients experienced mild hemiparesis and speech delays that resolved with therapy. Three patients experienced surgical complications requiring a second operation. The overall daily function and attentiveness of the patients improved. A complete CC should be considered as the initial procedure in lower-functioning children afflicted by absence, atonic, or myoclonic seizures. Severely affected higher-functioning children may also benefit from a complete CC, without clinically significant disconnection syndromes. A completion posterior CC may benefit patients in whom a prior anterior CC has failed.


Implications of coronary artery disease in heart failure with preserved ejection fraction.
This study investigated the characteristics, evaluation, prognostic impact, and treatment of coronary artery disease (CAD) in patients with heart failure and preserved ejection fraction (HFpEF). CAD is common in patients with HFpEF, but it remains unclear how CAD should be categorized, evaluated for, and treated in HFpEF. Clinical, hemodynamic, echocardiographic, treatment, and outcome characteristics were examined in consecutive patients with previous HFpEF hospitalizations who underwent coronary angiography. Of the 376 HFpEF patients examined, 255 (68%) had angiographically-proven CAD. Compared with HFpEF patients without CAD, patients with CAD were more likely to be men, to have CAD risk factors, and to be treated with anti-ischemic medications. However, symptoms of angina and heart failure were similar in patients with and without CAD, as were measures of cardiovascular structure, function, and hemodynamics. Compared with patients without CAD, HFpEF patients with CAD displayed greater deterioration in ejection fraction and increased mortality, independent of other predictors (hazard ratio: 1.71, 95% confidence interval: 1.03 to 2.98; p = 0.04). Complete revascularization was associated with less deterioration in ejection fraction and lower mortality compared with patients who were not completely revascularized, independent of other predictors (hazard ratio: 0.56, 95% confidence interval: 0.33 to 0.93; p = 0.03). CAD is common in patients with HFpEF and is associated with increased mortality and greater deterioration in ventricular function. Revascularization may be associated with preservation of cardiac function and improved outcomes in patients with CAD. Given the paucity of effective treatments for HFpEF, prospective trials are urgently needed to determine the optimal evaluation and management of CAD in HFpEF.


[Plasmid R1drd-19-mediated superoligomerization of the plasmid pACYC184in the recB mutant of Escherichia coli K12].
It was found that monomers of the pACYC184 plasmid undergo superoligomerization in a recB mutant of Escherichia coli K12 which is deficient in ATP-dependent RecBC nuclease and carries the drug resistance plasmid R1drd-19. The observed effect is specifically related to the ability of R1drd-19 to determine an ATP-dependent exonucleolytic activity which is functionally similar but not identical to the RecBC nuclease. The oligomerization of pACYC184 is accompanied by the formation of high-order circular structures, and this leads to elimination of the plasmid from cells growing under non-selective conditions.


DNACPR Decisions: Aligning Law, Guidance, and Practice.
Do not attempt cardiopulmonary resuscitation (DNACPR) decisions are a means to consider in advance the appropriateness of CPR measures if an acute crisis arises. During the COVID-19 pandemic, problems with such decisions, for example the putting in place of DNACPR decisions for all residents of certain care homes, received a lot of attention, prompting a Care Quality Commission (CQC) report with recommendations for improvement. Building on the CQC report, our article addresses a cluster of legal uncertainties surrounding DNACPR decisions, in particular about the grounds for such decisions and the correct procedures for the legally required consultation, including with whom to consult. This article will also analyse commonly used DNACPR forms, as well as the Recommended Summary Plan for Emergency Care and Treatment (ReSPECT) form, which aims to incorporate DNACPR decisions as part of more holistic end-of-life care planning. The analysis shows that all forms exhibit shortcomings in reflecting the legal requirements for DNACPR decisions. We recommend a number of changes to the forms aimed at rendering DNACPR practice compliant with the law and more protective of the person's human rights.


The relationship between bronchial immunopathology and hyperresponsiveness in asthma.
Physiological and Immunopathological parameters were investigated in 15 patients with diagnosed asthma, and 6 non-asthmatics presenting with other chest symptoms. The 15 symptom-free asthmatics expressed bronchohyperresponsiveness with a mean provocative dose producing a 20% fall in forced expiratory volume in one second (PD20FEV1) of 1 mg histamine. None of the non-asthmatics responded to 16 mg histamine. Twenty four hours later bronchoscopy was performed and endobronchial biopsies were obtained. Histological staining of frozen biopsy sections revealed a mononuclear cell infiltrate in all 15 asthmatics, while only 1 of the 6 non-asthmatics showed mild inflammation. Monoclonal antibodies were used to identify subsets of lymphocytes, activation markers, macrophages, and HLA-DR expression within the peribronchial infiltrates. In all samples, activated T-cells and macrophages were identified and HLA-DR expression was found to be raised, but the CD4: CD8 ratio was highly variable. No clear relationship was found between cellular distribution and measured lung function parameters. A highly significant correlation was found between the level of HLA-DR expression on the infiltrating cells (quantified microdensitometrically) and bronchial hyperresponsiveness. These results show for the first time that a chronic T-cell-mediated immune response is present in the bronchial tissue of asymptomatic asthmatics, and that the HLA-DR expression promoted correlates with the hyperresponsive status. These data promote the hypothesis that a T-cell-mediated response contributes to a predisposition to bronchial hyperresponsiveness in asthmatics.


Exploring the Symbiotic Mechanism of a Virus-Mediated Endophytic Fungus in Its Host by Dual Unique Molecular Identifier-RNA Sequencing.
The symbiosis of endophytes and plants is universal in nature. However, how endophytes grow in plants is not entirely clear. Previously, we reported that a virus-infected fungal pathogen could grow in plants as an endophyte. In this study, we utilized Sclerotinia sclerotiorum strain DT-8, a virus-mediated endophyte, to investigate the mechanism of symbiosis with rapeseed by dual unique molecular identifier-RNA sequencing (dual-UMI RNA-seq). We found that the expressions of genes encoding S. sclerotiorum amylase/glucoamylase, glucose transporters, and rapeseed sugars will eventually be exported transporter 11 (SWEET11) were upregulated. It suggested that strain DT-8 might utilize plant starch as a nutrient. The defense systems of rapeseed were also activated, such as production of reactive oxygen species, phenylpropanoids, and brassinin, to control the growth of strain DT-8, while strain DT-8 counteracted host suppression by producing effector-like proteins, detoxification enzymes, and antioxidant components. Moreover, rapeseed also upregulated pectate lyase and pectinesterase genes to facilitate the colonization by strain DT-8. Our findings provide novel insights into the interaction of virus-mediated endophytes and their hosts that warrant further study. IMPORTANCE Although endophytes are widespread in nature, the interactions between endophytes and their hosts are still not fully understood. Members of a unique class of endophytes, the virus-mediated endophytic fungi, are continuously being discovered and have received wide attention. In this study, we investigated the interaction between a mycovirus-mediated endophytic fungus and its host rapeseed by using dual-UMI RNA-seq. According to the dual-UMI RNA-seq results, an aerial view of symbiotic mechanism under balanced regulation was suggested. This research expands our understanding of the symbiotic mechanisms of virus-fungus-plant interactions and could establish a foundation for the further development of practical application with virus-mediated hypovirulent fungi.


Genome-wide analysis of the SCAMPs gene family of soybean and functional identification of GmSCAMP5 in salt tolerance.
The effect of salt damage on plants is mainly caused by the toxic effect of Na+. Studies showed that the secretory carrier membrane proteins were associated with the Na+ transport. However, the salt tolerance mechanism of secretory carrier protein (SCAMP) in soybean was yet to be defined. In this study, ten potential SCAMP genes distributed in seven soybean chromosomes were identified in the soybean genome. The phylogenetic tree of SCAMP domain sequences of several plants can divide SCAMPs into two groups. Most GmSCAMPs genes contained multiple Box4, MYB and MYC cis-elements indicated they may respond to abiotic stresses. We found that GmSCAMP1, GmSCAMP2 and GmSCAMP4 expressed in several tissues and GmSCAMP5 was significantly induced by salt stress. GmSCAMP5 showed the same expression patterns under NaCl treatment in salt-tolerant and salt-sensitive soybean varieties, but the induced time of GmSCAMP5 in salt-tolerant variety was earlier than that of salt-sensitive variety. To further study the effect of GmSCAMP5 on the salt tolerance of soybean plants, compared to GmSCAMP5-RNAi and EV-Control plants, GmSCAMP5-OE had less wilted leave and higher SPAD value. Compared to empty vector control, less trypan blue staining was observed in GmSCAMP5-OE leaves while more staining in GmSCAMP5-RNAi leaves. The Na+ of GmSCAMP5-RNAi plants leaves under NaCl stress were significantly higher than that in EV-Control plants, while significantly lower Na+ in GmSCAMP5-OE plants than in that EV-Control plants. The contents of leaves K+ of GmSCAMP5-RNAi, EV-Control, and GmSCAMP5-OE plants under NaCl stress were opposite to that of leaves Na+ content. Finally, salt stress-related genes NHX1, CLC1, TIP1, SOD1, and SOS1 in transformed hairy root changed significantly compared with the empty control. The research will provide novel information for study the molecular regulation mechanism of soybean salt tolerance.


Homer 1a gates the induction mechanism for endocannabinoid-mediated synaptic plasticity.
At hippocampal excitatory synapses, endocannabinoids (eCBs) mediate two forms of retrograde synaptic inhibition that are induced by postsynaptic depolarization or activation of metabotropic glutamate receptors (mGluRs). The homer family of molecular scaffolds provides spatial organization to regulate postsynaptic signaling cascades, including those activated by mGluRs. Expression of the homer 1a (H1a) immediate-early gene produces a short homer protein that lacks the domain required for homer oligomerization, enabling it to uncouple homer assemblies. Here, we report that H1a differentially modulates two forms of eCB-mediated synaptic plasticity, depolarization-induced suppression of excitation (DSE) and metabotropic suppression of excitation (MSE). EPSCs were recorded from cultured hippocampal neurons and DSE evoked by a 15 s depolarization to 0 mV and MSE evoked by a type I mGluR agonist. Expression of H1a enhanced DSE and inhibited MSE at the same synapse. Many physiologically important stimuli initiate H1a expression including brain-derived neurotrophic factor (BDNF). Treating hippocampal cultures with BDNF increased transcription of H1a and uncoupled homer 1c-GFP (green fluorescent protein) clusters. BDNF treatment blocked MSE and enhanced DSE. Thus, physiological changes in H1a expression gate the induction pathway for eCB-mediated synaptic plasticity by uncoupling mGluR from eCB production.