Point of care, bone marrow mononuclear cell therapy in ischemic heart failure patients personalized for cell potency: 12-month feasibility results from CardiAMP heart failure roll-in cohort.
Heart failure following myocardial infarction (MI) is a potentially lethal problem with a staggering incidence. The CardiAMP Heart Failure trial represents the first attempt to personalize marrow-derived cell-based therapy to individuals with cell characteristics associated with beneficial responses in prior trials. Before the initiation of the randomized pivotal trial, an open-label "roll-in cohort" was completed to ensure the feasibility of the protocol's procedures. Patients with chronic post-MI heart failure (NYHA class II-III) receiving stable, guideline-directed medical therapy with a left ventricular ejection fraction between 20 and 40% were eligible. Two weeks prior to treatment, a ~ 5 mL bone marrow aspiration was performed to examine "cell potency". On treatment day, a 60 mL bone marrow aspiration, bone marrow mononuclear cell (BM MNC) enrichment and transendocardial injection of 200 million BM MNC's was performed in a single, point of care encounter. Patients were then followed to assess clinical outcomes. The cell potency small volume bone marrow aspirate, the 60 mL bone marrow aspirate, and transendocardial injections were well tolerated in 10 patients enrolled. There were no serious adverse events related to bone marrow aspiration or cell delivery. Improvement in 6-min walk distance was observed at 6 months (+47.8 m, P = 0.01) and trended to improvement at 12 months (+46.4, P = 0.06). Similarly, trends to improved NYHA heart failure functional class, quality of life, left ventricular ejection fraction and recruitment of previously akinetic left ventricular wall segments were observed. All CardiAMP HF protocol procedures were feasible and well tolerated. Favorable functional, echo and quality of life trends suggest this approach may offer promise for patients with post MI heart failure. The randomized CardiAMP Heart Failure pivotal trial is underway to confirm the efficacy of this approach. https://clinicaltrials.gov/ct2/show/NCT02438306.


Application of horizontal staircase electrophoresis in agarose minigels to the random intergenic spacer analysis of clinical samples.
The random intergenic spacer analysis is a recently developed technique for the study of microbial populations. The bacterial intergenic spacer (ITS) is located between 16S rRNA and 23S rRNA genes and presents different length and sequence among bacterial species. Therefore, the amplicons can be separated by electrophoresis commonly performed at low voltage during several hours. Although this technique is especially useful for unculturable microorganisms, it has not been applied before to clinical sample analysis. As these samples have a limited number of bacterial species, the size of the gels may be reduced to facilitate their handling and to reduce the running time. To obtain maximum separation among the ITS bands, we analysed in this work different electrophoretical conditions including staircase electrophoresis, a technique based on the application of several voltage steps. The results obtained showed a different behaviour of the electrical resistance during the performance of submarine horizontal and vertical staircase electrophoresis. In the first case the resistance decreased during most of the running time whereas in the second case it increased. Here, we show that the performance of horizontal staircase electrophoresis reduces the running time more than 80% with respect to conventional electrophoresis at low voltages. This procedure was applied to the separation of ITS bands from bacterial DNA present in a tissue from a vocal cord biopsy. The sequencing of these bands allowed their identification. This new procedure may be very useful in the rapid diagnosis of bacteria present in human, animal and plant tissues.


The Influence of Betulin and Its Derivatives EB5 and ECH147 on the Antioxidant Status of Human Renal Proximal Tubule Epithelial Cells.
Betulin and its derivatives, 28-propyne derivative EB5 and 29-diethyl phosphonate analog ECH147, are promising compounds in anti-tumor activity studies. However, their effect on kidney cells has not yet been studied. The study aimed to determine whether betulin and its derivatives-EB5 and ECH147-influence the viability and oxidative status of human renal proximal tubule epithelial cells (RPTECs). The total antioxidant capacity of cells (TEAC), lipid peroxidation product malondialdehyde (MDA) level, and activity of antioxidant enzymes (SOD, CAT, and GPX) were evaluated. Additionally, the mRNA level of genes encoding antioxidant enzymes was assessed. Cisplatin and 5-fluorouracil were used as reference substances. Betulin and its derivatives affected the viability and antioxidant systems of RPTECs. Betulin strongly reduced TEAC in a concentration-dependent manner. All tested compounds caused an increase in MDA levels. The activity of SOD, CAT, and GPX, and the mRNA profiles of genes encoding antioxidant enzymes depended on the tested compound and its concentration. Betulin showed an cisplatin-like effect, indicating its nephrotoxic potential. Betulin derivatives EB5 and ECH147 showed different impacts on the antioxidant system, which gives hope that these compounds will not cause severe consequences for the kidneys in vivo.


Chronic fatigue syndrome is associated with metabolic syndrome: results from a case-control study in Georgia.
We hypothesized that persons with chronic fatigue syndrome (CFS) would have a higher prevalence of metabolic syndrome compared with well controls, and that unwell persons with insufficient symptoms or fatigue for CFS (termed ISF) would have a prevalence of metabolic syndrome intermediate between those with CFS and the controls. We also sought to examine the relationship between metabolic syndrome and measures of functional impairment, fatigue, and other symptoms. Our analysis was based on a population-based case-control study conducted in metropolitan, urban, and rural areas of Georgia, United States, between September 2004 and July 2005. There were 111 persons with CFS, 259 with ISF, and 123 controls. Metabolic syndrome was determined based on having at least 3 of 5 standard risk components (abdominal obesity, high triglycerides, high blood pressure, elevated fasting glucose, and decreased high-density lipids) according to the National Cholesterol Education Program Adult Treatment Panel III definition. Persons with CFS were 2-fold as likely to have metabolic syndrome (odds ratio = 2.12, confidence interval = 1.06, 4.23) compared with the controls. There was a significant graded relationship between the number of metabolic syndrome factors and CFS; each additional factor was associated with a 37% increase in likelihood of having CFS. The association of ISF with metabolic syndrome was weaker (odds ratio = 1.72, confidence interval = 0.94-3.16). Among persons with CFS, the number of metabolic syndrome factors was significantly correlated with worse fatigue on a standardized summary measure of fatigue (r = 0.20, P = .04). In conclusion, CFS was associated with metabolic syndrome, which further exacerbated fatigue.


Threshold in stage-specific embryonic glycotypes uncovered by a full portrait of dynamic N-glycan expression during cell differentiation.
Although various glycoforms appear to participate independently in multiple molecular interactions in cellular adhesion that contribute to embryogenesis and organogenesis, a full portrait of the glycome diversity and the effect of the structural variations of cellular glycoforms on individual cell stages in proliferation and differentiation remain unclear. Here we describe a novel concept for the characterization of dynamic glycoform alteration during cell differentiation by means of "glycoblotting-based cellular glycomics," the only method allowing for rapid and quantitative glycan analysis. We demonstrated that processes of dynamic cellular differentiation of mouse embryonic carcinoma cells, P19CL6 and P19C6, and mouse embryonic stem cells into cardiomyocytes or neural cells can be monitored and characterized quantitatively by profiling entire N-glycan structures of total cell glycoproteins. Whole N-glycans enriched and identified by the glycoblotting method (67 glycans for P19CL6, 75 glycans for P19C6, and 72 glycans for embryonic stem cells) were profiled and bar-coded quantitatively with respect to the ratio of subgroups composed of characteristic glycoforms, namely glycotypes.


Primary biliary cirrhosis: further biochemical and immunological characterization of mitochondrial antigens.
The nature of mitochondrial PBC-related antigens has been investigated with radioimmunoassay (RIA) and immunoblotting methods. The major antigen(s) was located by RIA in beef heart mitochondria, submitochondrial particles, chloroform-extracted F1-ATPase and Complex III. Cross-competition RIA experiments showed that the same antigen is present in all the above samples but at different concentrations. The antigen is not present in purified F1-ATPase, cytochrome oxidase, the oligomycin sensitivity conferring protein (OSCP), Factor6, or the Transhydrogenase. Immunoblot analysis of the above mitochondrial proteins revealed two PBC-related antigens (apparent molecular weights of 70 KD and 60 KD) whose distribution in the various proteins and protein complexes correlated well with the antigens determined by RIA. Immunoblot analysis of mitochondrial antigens was carried out using sera from normal subjects and from patients with PBC and with different autoimmune diseases (AID). Only PBC sera reacted with the 70 KD and 60 KD antigens. The PBC antigen detected by RIA in submitochondrial particles and the chloroform-F1-ATPase could be blocked by Mersalyl, suggesting its relationship to the mitochondrial 'M2' antigen. Furthermore, the antigenicity of the 70 KD peptide was shown by immunoblotting to be dependent upon mercaptoethanol. Thus, not only is the antigenicity of the 70 KD component dependent on a sulphur group, but the sulphur must be in the reduced form.


Variability in tablet fragment weights when splitting unscored cyclobenzaprine 10 mg tablets.
To determine the weight variation and calculated dosing variability of tablet fragments upon splitting unscored cyclobenzaprine hydrochloride 10 mg tablets using two common tablet splitting devices. Comparative pharmaceutics study. Pharmacy school laboratory. Not applicable. Unscored cyclobenzaprine hydrochloride 10 mg tablets from one generic manufacturer were split with a tablet splitter or a kitchen knife by a licensed pharmacist and two doctor of pharmacy students (n = 15 tablets for each method per participant). Fragment weights (FWs) were compared with the theoretical weights (TWs), which were calculated as one half of the mean weight of the tablets used in each part of the experiment; means, relative standard deviations (RSDs), and percentages of TW were also calculated. The mean weight before splitting the 45 tablets with the tablet splitter was 136.6 +/- 2.1 mg (TW = 68.3 mg). The mean FW after splitting was 67.9 +/- 7.9 mg. The RSD of 11.6% corresponded to a range of 69.4% to 130.2% of the TW and an estimated drug content of the split fragments between 3.47 mg and 6.51 mg. The mean weight before splitting the 45 tablets cut with a kitchen knife was 136.6 +/- 2.0 mg (TW = 68.3 mg). The mean FW was 68.0 +/- 15.7 mg with a RSD of 23.2%, corresponding to a range of 49.9% to 149.5% of the TW and an estimated drug content of the split fragments between 2.49 mg and 7.48 Tablet fragments obtained after splitting this generic cyclobenzaprine 10 mg product varied considerably in weight and estimated drug content. Accordingly, splitting cyclobenzaprine 10 mg tablets to achieve 5 mg doses could result in unpredictable dosing and therapeutic response.


The transmembrane tyrosines Y56, Y91 and Y167 play important roles in determining the affinity and transport rate of the rabbit proton-coupled peptide transporter PepT1.
The mammalian proton-coupled peptide transporter PepT1 is widely accepted as the major route of uptake for dietary nitrogen, as well as being responsible for the oral absorption of a number of classes of drugs, including beta-lactam antibiotics and angiotensin-converting enzyme (ACE) inhibitors. Using site-directed mutagenesis and zero-trans transport assays, we investigated the role of conserved tyrosines in the transmembrane domains (TMDs) of rabbit PepT1 as predicted by hydropathy plots. All the individual TMD tyrosines were substituted with phenylalanine and shown to retain the ability to traffic to the plasma membrane of Xenopus laevis oocytes. These single substitutions of TMD tyrosines by phenylalanine residues did not affect the proton dependence of peptide uptake, with all retaining wild-type PepT1-like pH dependence. Individual mutations of four of the nine TMD residue tyrosines (Y64, Y287, Y345 and Y587) were without measurable effect on PepT1 function, whereas the other five (Y12, Y56, Y91, Y167 and Y345) were shown to result in altered transport function compared to the wild-type PepT1. Intriguingly, the affinity of Y56F-PepT1 was found to be dramatically increased (approximately 100-fold) in comparison to that of the wild-type rabbit PepT1. Y91 mutations also affected the substrate affinity of the transporter, which increased in line with the hydrophilicity of the substituted amino acid (F>Y>Q>R). Y167 was demonstrated to play a pivotal role in rabbit PepT1 function since Y167F, Y167R and Y167Q demonstrated very little transport function. These results are discussed with regard to a proposed mechanism for PepT1 substrate binding.


Potentiation of sodium butyrate-induced apoptosis by vanadate in human promyelocytic leukemia cell line HL-60.
Vanadate (10 microM ), a potent inhibitor of tyrosine phosphatase, added simultaneously potentiated the sodium butyrate (BuONa)-induced growth inhibition. Furthermore, at 1 mM BuONa alone, after 96 h of incubation, about 20 +/- 5% of cells exhibited the morphological characteristic of apoptosis, as established by nuclear changes (condensed and fragmented nuclei) and decrease in cell size. After treatment of cells with 1 mM BuONa in the presence of 10 microM vanadate, apoptotic cells became more abundant; 90 +/- 3% of cells presented morphological characteristics of apoptosis after 96 h of incubation. Flow cytometric measurement of DNA content demonstrated the accumulation of cells in G1 phase after 72 h of incubation with 1 mM BuONa alone. In the presence of vanadate (10 microM ), accumulation of cells in G1 phase appeared after shorter times of incubation (48 h) with BuONa. A substantial increase in the proportion of cells with degraded DNA characteristic of apoptosis was observed after 48- to 72-h incubation with BuONa in the presence of vanadate. BuONa-induced apoptosis was accompanied by the increase of tyrosine phosphorylation of cellular proteins pp37 and pp97. Our results raised the possibility that regulation of tyrosine phosphorylation of pp37 and pp97 is an important event that heralds the BuONa-induced apoptosis.


Mucin Binding Reduces Colistin Antimicrobial Activity.
Colistin has found increasing use in treating drug-resistant bacterial lung infections, but potential interactions with pulmonary biomolecules have not been investigated. We postulated that colistin, like aminoglycoside antibiotics, may bind to secretory mucin in sputum or epithelial mucin that lines airways, reducing free drug levels. To test this hypothesis, we measured binding of colistin and other antibiotics to porcine mucin, a family of densely glycosylated proteins used as a surrogate for human sputum and airway mucin. Antibiotics were incubated in dialysis tubing with or without mucin, and concentrations of unbound antibiotics able to penetrate the dialysis tubing were measured over time using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The percentage of antibiotic measured in the dialysate after 4 h in the presence of mucin, relative to the amount without mucin, was 15% for colistin, 16% for polymyxin B, 19% for tobramycin, 52% for ciprofloxacin, and 78% for daptomycin. Antibiotics with the strongest mucin binding had an overall polybasic positive charge, whereas those with comparatively little binding were less basic. When comparing MICs measured with or without added mucin, colistin and polymyxin B showed >100-fold increases in MICs for multiple Gram-negative bacteria. Preclinical evaluation of mucin binding should become a standard procedure when considering the potential pulmonary use of new or existing antibiotics, particularly those with a polybasic overall charge. In the airways, mucin binding may reduce the antibacterial efficacy of inhaled or intravenously administered colistin, and the presence of sub-MIC effective antibiotic concentrations could result in the development of antibiotic resistance.


Internet addiction in adolescents: Role of family, personality and comorbid psychopathology in school children in Eastern India.
There is an increasing prevalence of internet addiction among adolescents during the COVID-19 pandemic, but very few Indian studies have assessed and taken into account various factors that can explain internet addiction in this vulnerable population. We examine the differences in family functioning, temperament, character and psychopathology in adolescents with and without internet addiction. 1000 adolescents from urban middle-class families were included in this cross-sectional, two-randomized-group designed, comparative study. Clinical and control group population were selected from high schools. Those with severe internet addiction were compared to those with no addiction. Internet Addiction Test, Temperament and Character Inventory, Devereux Scale of Mental Disorders and McMaster Family Assessment Device were administered along with General Health and CRAFFT Questionnaire as screening tool. Mann-Whitney U test was done along with Spearman's rank-difference coefficient of correlation. Adolescents with internet addiction had high novelty seeking and low persistence. Internet addiction was also associated with conduct problems and depression. There was a significant positive association between depression and years of internet usage. Family of adolescents with internet addiction had increased difficulty in problem solving, communication, affective responsiveness, affective involvement and behavior control. Adolescents with internet addiction have temperament difficulties, more psychopathology and belong to dysfunctional families. Since the family plays a central role in an Indian context, family-focused strategies must also be included in the management of internet addiction.


The development and testing of the nursing teamwork survey.
There is a lack of an acceptable, reliable, and valid survey instruments to differentiate levels of nursing teamwork on inpatient units in acute care facilities. The aim of this study was to test the psychometric soundness of the Nursing Teamwork Survey (NTS). The survey was administered to 1,758 inpatient nursing staff members using the NTS (return rate = 56.9%), and measures of content, predictive (concurrent), and construct (factorial, contrast, and convergent) validity were completed. Content validity was established by a panel of experts. Concurrent validity showed a significant correlation between teamwork scores and an imbedded question related to overall satisfaction with teamwork (r = .633, p < .001). The exploratory factor analysis on a random half of the sample predicted a 33-item five-factor solution, whereas the confirmatory factor analysis on the remaining half of the sample confirmed the factor structure (comparative fit index = .884, root mean square error of approximation = 0.055, standardized root mean square residual = 0.045). Contrast validity showed that staff in a non-inpatient unit did not answer the questions in the same way (rWG(J) = .25) as the inpatient unit staff (rWG(J) > .90). Convergent validity of the teamwork tool was measured by correlating the Teamwork subscale of the Safety Attitudes Questionnaire with the NTS (r = .76, p < .01). The NTS had good test-retest reliability (r = .92 for overall 33 items; r = .77 to.87 for the five subscales) and internal consistency (alpha = .94 for overall items; alpha = .74 to.85 for the subscales). Aggregation of individual-level responses to the unit level was supported by intraclass correlation coefficient 1 = .16 (p < .001), intraclass correlation coefficient 2 = .9 (p < .001), and mean rWG(J) = .98. The NTS was demonstrated to have good psychometric properties. Further NTS research should include testing the tool in hospitals with varying characteristics and exploring the links to clinical and operational outcomes.


Nutritional considerations in inflammatory bowel diseases.
Although many foods have been suggested to play a role in the cause of IBD, there are not yet definitive data to support diet as a cause of either CD or UC. Malnutrition is a common occurrence in IBD, and this must be considered in the treatment of these diseases. Nutritional support in IBD has limited use as primary therapy (Table 2). Even though parenteral and enteral nutrition have been associated with remission, relapse frequently occurs when normal food intake is resumed. Likewise, fistulae may resolve with aggressive, nutritional therapy, but they frequently recur with reinstitution of food. In short bowel syndrome caused by extensive intestinal resection performed in CD, parenteral nutrition provides an important mode of therapy. In addition, perioperative use of nutritional support may decrease the incidence of postoperative complications in patients who are malnourished. Nutritional support in pediatric patients with CD who have growth failure has been effective in stimulating growth.


[SENTIERI-ReNaM: Rationale and objectives].
The purpose of the SENTIERI-ReNaM Project is to analyse the incidence of mesothelioma in Italian National Priority Contaminated Sites (NPCSs) in order to estimate the health impact of asbestos on resident populations, disentangling the role of occupational and environmental exposures. SENTIERI Project has provided the relevant information on geographic and demographic structure of NPCSs and on existing sources of contamination. The Italian National Mesothelioma Registry (ReNaM), that covers the whole country through its Regional Operational Centres (CORs), has made available the procedures for estimating the incidence of mesothelioma in NPCSs and for assessing occupational and environmental asbestos exposure of the individual cases. The synergy between these two epidemiological surveillance systems lay also the ground for communication programmes with the affected communities.


Integrin modulating factor-1: a lipid that alters the function of leukocyte integrins.
The avidity of integrin CR3 (also known as alpha M beta 2, Mac-1, Mo-1, and CD11b/CD18) may be reversibly altered without changes in the number of cell surface receptors. Here we describe a molecule termed integrin modulating factor (IMF-1), which controls CR3 avidity. Addition of IMF-1 to polymorphonuclear leukocytes (PMNs) or to purified CR3 causes enhanced binding of ligand. IMF-1 is not present in resting PMNs, but stimulation of cells results in a transient rise in IMF-1 content that parallels a transient rise in CR3 activity. We suggest that PMNs control adhesivity by controlling synthesis of IMF-1, which then acts as an allosteric activator of leukocyte integrins. IMF-1 is an acidic, amphiphilic molecule of Mr340 +/- 16 that does not contain ester, phosphate, amide, sialic acid, or glycosidic or vicinal hydroxyl functionalities, but does contain a carbon-carbon double bond. These results suggest that IMF-1 is an unsaturated fatty acid or an isoprenoid acid.


Is electroconvulsive therapy effective as augmentation in clozapine-resistant schizophrenia?
Clozapine is considered to be the most effective antipsychotic drug for patients with treatment resistant schizophrenia, but up to a third of the patients do not respond to this treatment. Various strategies have been tried to augment the effect of clozapine in non-responders, one of these strategies being electroconvulsive therapy. However, its efficacy and safety are not yet clear. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified six systematic reviews including 55 studies, among them six randomized controlled trials addressing clozapine-resistant schizophrenia. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded electroconvulsive therapy probably augments response to clozapine in patients with treatment resistant schizophrenia, but it is not possible to determine if it leads to cognitive adverse effects because the certainty of the evidence is very low.


Escherichia coli isolates' serotypes, genotypes, and virulence genes and clinical coliform mastitis severity.
Dairy cattle with clinical mastitis caused by Escherichia coli exhibit a wide range of disease severity, from mild, with only local inflammatory changes of the mammary gland, to severe, with significant systemic derangement. The present study was designed to examine the relationship between serotype and virulence genes of E. coli mastitis isolates, different levels of systemic disease severity, and farm from which the E. coli strain was obtained. One hundred twenty-three E. coli milk isolates were obtained from cows with clinical mastitis of varying systemic disease severity from 6 different farms. No predominant serotype was identified by farm or by systemic disease severity; however, the most frequent serotype, O158:NM (n = 3), was isolated from cows in the moderate severity group. Virulence genes evaluated were identified infrequently and were not associated with systemic disease severity. Evaluation of genetic similarity showed no clustering assigned by farm or mastitis severity based on systemic disease signs. We concluded that a high degree of genotypic variability is characteristic of E. coli strains causing clinical mastitis within and between different farms and systemic severity groups, and that specific cow factors probably play a more important role in determining systemic disease severity.


Nonsurgical treatment of teenagers with high AC/A ratio esotropia.
Nonsurgical treatment options commonly prescribed for teenagers with high AC/A ratios are progressive lens spectacles, single vision lens spectacles, bifocal contact lenses, and monovision. The gold standard treatment for high AC/A ratios in patients with esotropia is bifocal spectacles, but they are not cosmetically acceptable for most teenagers. However, excellent binocularity is often sacrificed with the alternative treatment options. Quality of life surveys acknowledge that poor cosmesis can have a negative psychosocial impact on individuals. Therefore, it is often necessary for practitioners to strike a balance between good psychosocial health and best visual potential with treatment options other than bifocal spectacles.


The dexmedetomidine concentration required after remifentanil anesthesia is three-fold higher than that after fentanyl anesthesia or that for general sedation in the ICU.
The general dexmedetomidine (DEX) concentration required for sedation of intensive care unit patients is considered to be approximately 0.7 ng/mL. However, higher DEX concentrations are considered to be required for sedation and/or pain management after major surgery using remifentanil. We determined the DEX concentration required after major surgery by using a target-controlled infusion (TCI) system for DEX. Fourteen patients undergoing surgery for abdominal aortic aneurysms (AAA) were randomly, double-blindly assigned to two groups and underwent fentanyl- or remifentanil-based anesthetic management. DEX TCI was started at the time of closing the peritoneum and continued for 12 hours after stopping propofol administration (M0); DEX TCI was adjusted according to the sedation score and complaints of pain. The doses and concentrations of all anesthetics and postoperative conditions were investigated. Throughout the observation period, the predicted plasma concentration of DEX in the fentanyl group was stable at approximately 0.7 ng/mL. In contrast, the predicted plasma concentration of DEX in the remifentanil group rapidly increased and stabilized at approximately 2 ng/mL. The actual DEX concentration at 540 minutes after M0 showed a similar trend (0.54±0.14 [fentanyl] versus 1.57±0.39 ng/mL [remifentanil]). In the remifentanil group, the dopamine dose required and the duration of intubation decreased, and urine output increased; however, no other outcomes improved. The DEX concentration required after AAA surgery with remifentanil was three-fold higher than that required after AAA surgery with fentanyl or the conventional DEX concentration for sedation. High DEX concentration after remifentanil affords some benefits in anesthetic management.


Therapy Decision Support Based on Recommender System Methods.
We present a system for data-driven therapy decision support based on techniques from the field of recommender systems. Two methods for therapy recommendation, namely, Collaborative Recommender and Demographic-based Recommender, are proposed. Both algorithms aim to predict the individual response to different therapy options using diverse patient data and recommend the therapy which is assumed to provide the best outcome for a specific patient and time, that is, consultation. The proposed methods are evaluated using a clinical database incorporating patients suffering from the autoimmune skin disease psoriasis. The Collaborative Recommender proves to generate both better outcome predictions and recommendation quality. However, due to sparsity in the data, this approach cannot provide recommendations for the entire database. In contrast, the Demographic-based Recommender performs worse on average but covers more consultations. Consequently, both methods profit from a combination into an overall recommender system.


Seasonal control of tuberization in potato: conserved elements with the flowering response.
Fluctuations in day length determine the time to flower in many plants and in potato are critical to promote differentiation of tubers. Day length is perceived in the leaves and under inductive conditions these synthesize a systemic signal that is transported to the underground stolons to induce tuber development. Flowering tobacco shoots grafted into potato stocks promote tuberization in the stocks, indicating that the floral and tuber-inducing signals might be similar. We describe recent progress in the identification of the molecular mechanisms underlying day-length recognition in potato. Evidence has been obtained for a conserved function of the potato orthologs of the CONSTANS (CO) and FLOWERING LOCUS T (FT) proteins in tuberization control under short days (SDs). These observations indicate that common regulatory pathways are involved in both flowering and tuberization photoperiodic responses in plants.


Chlamydiae as etiologic agents in chronic undifferentiated spondylarthritis.
The majority of patients with Chlamydia-induced reactive arthritis do not present with the classic triad of arthritis, conjunctivitis/iritis, and urethritis. Moreover, acute chlamydial infections are often asymptomatic. The aim of the present study was to assess the prevalence of synovial Chlamydia trachomatis and Chlamydia pneumoniae infections in patients with chronic undifferentiated spondylarthritis (uSpA). Study patients met the European Spondylarthropathy Study Group criteria for SpA, without evidence of ankylosing spondylitis, psoriasis, inflammatory bowel disease, or preceding dysentery. Symptoms were present for >or=6 months. Each patient underwent a synovial biopsy; tissue and concomitantly obtained peripheral blood mononuclear cells (PBMCs) were analyzed by polymerase chain reaction (PCR) for C trachomatis and C pneumoniae DNA. Other data collected on the day of the biopsy included standard demographic information and medical history, including any known history of C trachomatis or C pneumoniae. Physical examination (including joint count, evaluation for dactylitis and/or enthesitis, and skin examination) and HLA-B27 typing were performed. Synovial tissue (ST) samples from 167 patients with osteoarthritis (OA) were used as controls. Twenty-six patients met the entry criteria and underwent synovial biopsy (25 knee, 1 wrist). Sixteen of them (62%) were positive for C trachomatis and/or C pneumoniae DNA (10 for C trachomatis, 4 for C pneumoniae, and 2 for both). PCR analysis of ST revealed the presence of Chlamydia significantly more frequently in patients with uSpA than in OA controls (P<0.0001). No specific clinical characteristics differentiated Chlamydia-positive from Chlamydia-negative patients. PBMCs from 4 of the 26 uSpA patients (15%) were positive for Chlamydia, and Chlamydia was found in ST from 2 of these 4 patients. No significant correlation between PCR positivity and HLA-B27 positivity was found. The frequency of Chlamydia-positive ST samples, as determined by PCR, was found to be significantly higher in patients with uSpA than in patients with OA. Our results suggest that in many patients with uSpA, chlamydial infection, which is often occult, may be the cause.


Awareness about barriers to medication adherence in cardiovascular patients and strategies used in clinical practice by Portuguese clinicians: a nationwide study.
Although much is known about cardiovascular patients' medication adherence, the extent to which clinicians perceive non-adherence as a barrier in clinical practice is little explored. Objective To evaluate knowledge and awareness about potential barriers to medication adherence, and to evaluate strategies used in clinical practice by Portuguese clinicians on how to foster medication adherence of patients undergoing secondary cardiovascular prevention. Setting Nominal Group Technique (NGT) at the University of Lisbon; online survey addressed to physicians working in primary and secondary care in Portugal. Method A narrative literature review was conducted in Pubmed to identify studies describing interventions targeted at physicians to manage medication adherence. The NGT included 12 allied healthcare professionals with recognized expertise in medication adherence and was organised in four phases, resulting in survey development. The survey was used in a cross-sectional national study where clinicians reported their knowledge and perceptions about patients' medication adherence and their daily practice. Main outcome measures Knowledge and awareness about barriers to medication adherence; and practice patterns. Results A total of 296 papers were identified, 26 of which were included. Four main topics were selected to be used in the NGT: adherence determinants, detecting non-adherence, fostering adherence, and educating physicians. NGT resulted in a survey, reaching 451 physicians, mostly practicing in primary care. Most had specific education on medication adherence and considered patient interviews and prescription records the most useful assessment methods. Nonetheless, many recognised often using clinical judgement to evaluate adherence in practice. Barriers to medication adherence were perceived to occur often during implementation. Most perceived reasons for uncontrolled hypertension were non-adherence to lifestyle recommendations and to medication. Less than half the physicians asked their patients if medication was taken. More useful enabling strategies included reducing daily doses, reviewing therapeutic options and motivational interventions. Conclusions Clinicians seem well informed about the importance of medication adherence and aware of problems encountered in practice. Limited time during medical appointment may be a barrier for better patient support.


'The character rests heavily within me': drama students as standardized patients in mental health nursing education.
WHAT IS KNOWN ON THE SUBJECT?: Standardized patient (SP) simulation is an internationally recognized learning strategy that has proven effective in enhancing nursing students' competencies necessary for mental health practice. WHAT DOES THIS PAPER ADD TO EXISTING KNOWLEDGE?: A deeper exploration of the process from the perspective of SPs and more particularly drama students, revealed the complexity they need to navigate and the personal vulnerability they are exposed to when creating an authentic learning opportunity for nursing students. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Their vulnerability justifies deeper consideration of support, as well as research on the ethical implications of SP simulation. Nursing students need to be well grounded in therapeutic communication before engaging with mental health users. This should include opportunities to question personal frames of reference that could hinder therapeutic engagement with diverse others. In future, the drama students can be involved in scenario development to enhance the authenticity of simulations. Introduction The effectiveness of Standardized patient (SP) simulation in enhancing students' mental health nursing competencies is well published. Nevertheless, the believable and accurate portrayal of a patient with a mental health issue during SP simulation is complex. Though vital to the creation of safe authentic learning experiences, the perspectives of SPs and particularly of drama students involved in SP simulation are unknown. Aim The aim of this paper is therefore to explore and describe the experiences of 11 drama students engaged in mental health simulations for nursing students. Method A qualitative approach was taken and data were gathered using various techniques. Findings The content analysis revealed that these SPs negotiated three roles during this interdisciplinary learning experience, namely of a facilitator of learning, a drama student and the person within. Discussion The study provided valuable insight into the world of an SP, including the complexities they navigate and the vulnerability they experience. Implications for Practice Nurse educators are alerted to SP's need for support and the necessity of establishing good interpersonal skills before nursing students enter the practice setting. Involvement of SPs in scenario development could enhance the authenticity of future simulations. The ethical implications of SP simulation requires further exploration.


¹H-NMR Profiling and Carbon Isotope Discrimination as Tools for the Comparative Assessment of Walnut (Juglans regia L.) Cultivars with Various Geographical and Genetic Origins-A Preliminary Study.
:The aim of the study was to investigate the differences between walnut genotypes of various geographical and genetic origins grown under the same or different environmental conditions. The biological material analyzed consisted in walnut kernels of 34 cultivars, nine advanced selections, and six hybrids harvested in 2015 and 2016, summing up to a total of 64 samples. The walnuts, walnut oil, and residue were characterized in respect to their chemical (proximate composition-fat, protein, nutritional value, fatty acids profile by ¹H-NMR) and carbon-13 isotopic composition. The data was used to statistically discriminate the cultivars according to composition, geographical area of origin, and year of harvest, comparing the Romanian cultivars, selections, and hybrids with the internationally available ones.


[Present state and future of the self-test in preventive medicine].
The preventive medicine changes from secondary prevention of early detection and early treatment to primary prevention of the avoidance of pathopoiesis and health-Crisis. In present state, there is no a clinical laboratory which should respond to this proposition of the fact with the convention at all. As well as clinical laboratory in the hospital, the clinical laboratory in preventive medicine has also been centralized to the Health screening facilities. The immediacy of The clinical laboratory which can be measured, when it wants to measure it, Is required in order to grasp "bio-information" for avoiding the crisis of the disease. It become important that simultaneously, some relating inspection items are measured a case in which it wants to attempt. It waits for the possibility of a disease state grasp from the self measuring device that it is convenient and that the accuracy is high for health-crisis and pathopoiesis avoidance as a primary prevention in order to rapidly improve the accuracy of the weather forecast by the launch of the meteorological satellite.


A study on the prevention of duodenal ulcer recurrence with pirenzepine.
A double-blind, controlled study with either 50 mg of pirenzepine or a placebo once a day was performed in 128 patients to determine the effect of pirenzepine against relapses of duodenal ulcer, the healing of the subjects' former ulcers having been confirmed endoscopically. The study lasted 12 months at longest; endoscopy was performed at 3,6,9 and 12 month intervals during the study, as well as when subjective symptoms developed. Cumulative non-relapse rates were obtained every 3 months according to the life expectancy table; at 3 and 6 months, they were 85.7% and 73.0% for the pirenzepine group and 67.9% and 49.0% for the placebo group, thus indicating significantly lower relapse rates in favour of the pirenzepine group (p less than 0.05). There was no significant difference between the two groups with regard to the 12-month cumulative non-relapse rate. Comparison of background factors in relapsed and non-relapsed cases suggested that relapses were more frequent among pirenzepine-treated patients who had required a shorter course of treatment or had received H2 antagonists in the treatment of their previous ulcer. Relapses of duodenal ulcer were closely correlated with relapses of subjective symptoms, but there was no significant difference between the pirenzepine group and the placebo group with regard to the frequency of subjective symptoms at the time of ulcer recurrence. Pirenzepine, like H2 antagonists, proved to prevent ulcer relapses temporarily. The relapse rate with the compound appeared to be higher in cases where the former ulcer had been treated with H2 antagonists.


Holistic Health of Two Spirit People in Canada: A Call for Nursing Action.
Purpose: In response to item 7.1 from the Missing and Murdered Indigenous Women and Girls Report (2019), calling on health service providers to recognize the importance in inclusive services with and for Indigenous peoples including Two Spirit, lesbian, bisexual, transgender, queer, questioning, intersex, and asexual (2SLGBTQQIA) peoples, we undertook a review of the literature to identify the gaps in understanding and to better situate the health and resiliencies of Two Spirit people in Canada. Method: We conducted a review of 13 articles related to the health and wellness of the Canadian Two Spirit community. Overall, there was a dearth of Two Spirit specific health-related information. Results: Identified themes were grounded in the holistic Medicine Wheel teachings. These themes directly parallel holistic nursing in their demonstration that health is complex, and that there are many facets that make up an individuals' health. Conclusion: Assessing the impact that colonization has had on the intersections of gender, race, sexuality, class, culture, and spirituality, Two Spirit people face unique health concerns. Considering the intersections of identity and structural barriers in place for this community, more research led by and in collaboration with the Two Spirit community is needed.


Acidic fibroblast growth factor (aFGF) is expressed in the neuronal and glial spinal cord cells of adult mice.
Fibroblast growth factors (FGFs) are known to be synthesized in the central nervous system (CNS) and to act on CNS cells in vitro, but less is known about their synthesis, expression, and role in vivo. In this work, using specific anti-acidic fibroblast growth factor (aFGF) antibodies, we have shown for the first time, by immunohistochemistry, that aFGF is expressed in spinal cord cells of young adult normal mice. This expression is predominant in the cell nucleus. Using immunohistochemical double staining procedures, we identified the cell type expressing aFGF as neurons, astrocytes, and oligodendrocytes, but for each type, cells were not all positively immunostained.


Occupational neutrophilic asthma.
Occupational asthma is typically associated with an eosinophilic bronchitis. The case of a 41-year-old woman who developed symptoms of asthma after occupational exposure to metal working fluids is reported. The diagnosis of asthma was confirmed by an forced expiratory volume in 1 s (FEV1) of 1.7 (59% predicted), with 11% reversibility after inhaled bronchodilator and a provocation concentration of methacholine to cause a fall in FEV1 of 20% (PC20) of 0.4 mg/mL. Induced sputum examination showed a marked neutrophilia. Over the next six months, serial sputum analyses confirmed the presence of a marked sterile neutrophilic bronchitis during periods of occupational exposure to metal working fluids, which resolved when the patient was away from work and recurred when she returned to work. The sputum findings were mirrored by corresponding changes in spirometry and PC20 methacholine. The findings indicate the occurrence of occupational asthma associated with an intense, sterile neutrophilic bronchitis after exposure to metal working fluids.


Heat shock proteins in maize.
The pattern of protein synthesis in roots of 3-day-old maize seedlings (Zea mays L.) is rapidly and dramatically altered when the incubation temperature is raised from 25 to 40 degrees C. One-dimensional sodium dodecyl sulfate gels reveal that although synthesis of the proteins observed at 25 degrees C continues at 40 degrees C, a new set of ;heat shock proteins' (hsp) is induced within 20 minutes of the temperature transition. The hsp have molecular weights of 87, 85, 79, 78, 77, 72, 70, 27, 22, and 18 kilodaltons. The 10 hsp are visible on autoradiograms but not on stained gels, suggesting that the proteins do not accumulate to any great extent.The induction of the hsp is transitory. With prolonged high temperature treatment, the synthesis of hsp continues for 4 hours in excised roots and for 8 hours in the roots of intact seedlings before declining sharply. Coincident to the decline in synthesis of the 10 hsp is the gradual increase in intensity of three new polypeptides having molecular weights of 62, 49.5, and 19 kilodaltons. These proteins begin to appear about the time that synthesis of the other 10 hsp becomes maximal.Shifting the temperature back to 25 degrees C also causes a decline in synthesis of hsp, but this decline occurs more rapidly than that seen during prolonged heat shock. A decrease in hsp synthesis becomes apparent 2 hours after the roots are returned to 25 degrees C.Shifting the temperature from 25 to 45 degrees C results in a pattern of protein synthesis different from that observed after a shift to 40 degrees C. Normal protein synthesis continues, except four proteins, which are produced in small amounts at lower temperatures, show greatly enhanced synthesis at 45 degrees C. These proteins have apparent molecular weights of 83, 81, 68, and 65 kilodaltons. Also, the 10 hsp listed above are not synthesized. It is suggested that at least two distinct high-temperature responses are present in maize, which may reflect the metabolic changes generated at different elevated temperatures.


Effect of iron depletion on long-term response to interferon-alpha in patients with chronic hepatitis C who previously did not respond to interferon therapy.
About half of patients with chronic hepatitis C treated with interferon will not have a biochemical or virological response. Several studies suggested that increased hepatic iron content may negatively influence the response to interferon. We conducted this prospective trial to evaluate the effect of iron depletion on the response to a repeat course of interferon in 20 chronic hepatitis C patients who previously had not responded to interferon. The patients underwent 500-ml phlebotomies every 2 weeks until iron deficiency was achieved. Patients were then started on a 6-month course of interferon alfa-2b (3 million units, t.i.w.). These patients required a mean of 6.0 (range, 1-14) phlebotomies to become iron deficient. ALT levels decreased in 18 of 20 patients and became normal in 4 patients. Mean ALT levels decreased from 154.2 to 87.9 U/L (p = 0.0006). At the end of 24 wk of interferon therapy, ALT levels were normal in 11 patients, 3 of whom had undetectable HCV RNA in the serum. One additional patient with abnormal ALT had undetectable HCV RNA. After 6 months of follow-up, one of the HCV RNA negative patients relapsed with reappearance of HCV RNA and elevation of ALT. In summary, 15% of chronic hepatitis C patients who previously failed interferon now had a sustained response to interferon therapy that was preceded by iron depletion.


Studies on the use of neem products for removal of ammonia from brackishwater.
Laboratory experiments were carried out to investigate the ammonia removal from brackishwater (Salinity 16 +/- 1 ppt) using natural plant products such as seed powder and seed oil from neem (Azadirachta indica) and commercially available neem products-neemazal and neemgold. The experimental results showed that ammonia removal was effective with 90 mg/l of neem oil, whereas, neem seed powder at 90 mg/l registered an increase in ammonia levels throughout the course of the experiment. Neem oil, neemazal, and neemgold at 90 mg/l were effective in decreasing the total ammonia nitrogen (TAN) level of 0.40-0.45 mg/l in 96 h. The effect of initial ammonia concentrations on the ammonia removal using neem oil revealed that percentage ammonia removal decreased with an increase in initial ammonia concentration.


Giving a larger amount or a larger proportion: Stimulus format impacts children's social evaluations.
Young children show remarkably sophisticated abilities to evaluate others. Yet their abilities to engage in proportional moral evaluation undergoes protracted development. Namely, young children evaluate someone who shares absolutely more as being "nicer" than someone who shares proportionally more (e.g., sharing 3-out-of-6 is nicer than sharing 2-out-of-3, because 3 > 2, even though 3/6 < 2/3), whereas adults think the opposite. We investigate the hypothesis that this prior work underestimates children's proportional social reasoning by relying on discrete and spatially separated quantities (e.g., individual stickers), which can hinder proportional reasoning even outside social contexts. In three experiments we examine whether 4- and 5-year-old children's social evaluations are impacted by the discreteness and spatial separation of the resource and compare their behavior to adults (18 to 63 years; across all samples: 38% girls/women, 62% boys/men; no other demographic data was collected). We find that children are sensitive to these features: when the resource was divided into discrete units (Experiment 1) or spatially separated (Experiment 2) children were more likely to use absolute amount, as opposed to proportion, relative to when the resources were not divided and remained spatially connected. However, adults were highly sensitive to proportion regardless of the display's perceptual features (Experiment 3), and children's use of proportion remained below adult-levels. These results suggest that perceptual features influence children's use of absolute versus proportional information in their social evaluations, which has theoretical and methodological implications for understanding children's conceptions of fairness. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Stereoselective Assembly of Gigantic Chiral Molybdenum Blue Wheels Using Lanthanide Ions and Amino Acids.
The synthesis of chiral polyoxometalates (POMs) is a challenge because of the difficulty to induce the formation of intrinsically chiral metal-oxo frameworks. Herein we report the stereoselective synthesis of a series of gigantic chiral Mo Blue (MB) POM clusters 1-5 that are formed by exploiting the synergy between coordinating lanthanides ions as symmetry breakers to produce MBs with chiral frameworks decorated with amino acids ligands; these promote the selective formation of enantiopure MBs. All the compounds share the same framework archetype, based on {Mo124Ce4}, which forms an intrinsically chiral Δ or Λ configurations, controlled by the configurations of functionalized chiral amino acids. The chirality and stability of 1-5 in solution are confirmed by circular dichroism, 1H NMR, and electrospray ion mobility-mass spectrometry studies. In addition, the framework of the {Mo124Ce4} MB not only behaves as a host able to trap a chiral {Mo8} cluster that is not accessible by traditional synthesis but also promotes the transformation of tryptophan to kynurenine in situ. This work demonstrates the potential and applicability of our synthetic strategy to produce gigantic chiral POM clusters capable of host-guest chemistry and selective synthetic transformations.


Stress Responses in Alfalfa (Medicago sativa L.): I. Induction of Phenylpropanoid Biosynthesis and Hydrolytic Enzymes in Elicitor-Treated Cell Suspension Cultures.
Alfalfa (Medicago sativa L.) cell suspension cultures accumulated high concentrations of the pterocarpan phytoalexin medicarpin, reaching a maximum within 24 hours after exposure to an elicitor preparation from cell walls of the phytopathogenic fungus Colletotrichum lindemuthianum. This was preceded by increases in the extractable activities of the isoflavonoid biosynthetic enzymes l-phenylalanine ammonia-lyase, cinnamic acid 4-hydroxylase, 4-coumarate coenzyme A-ligase, chalcone synthase, chalcone isomerase, and isoflavone O-methyltransferase. Pectic polysaccharides were weak elicitors of phenylalanine ammonia-lyase activity but did not induce medicarpin accumulation, whereas reduced glutathione was totally inactive as an elicitor in this system. The fungal cell wall extract was a weak elicitor of the lignin biosynthetic enzymes, caffeic acid O-methyltransferase and coniferyl alcohol dehydrogenase, but did not induce appreciable increases in the activities of the hydrolytic enzymes chitinase and 1,3-beta-d-glucanase. The results are discussed in relation to the activation of isoflavonoid biosynthesis in other legumes and the development of the alfalfa cell culture system as a model for studying the enzymology and molecular biology of plant defense expression.


Iron chelation therapy: clinical effectiveness, economic burden and quality of life in patients with iron overload.
This study of UK patients examines clinical, health-related quality of life (HRQOL) and economic outcomes associated with iron chelation therapy (ICT). Desferrioxamine (DFO) (Desferal; Novartis, Switzerland) and Deferiprone (Ferriprox; Apotex, Canada) are ICTs used to treat iron overload. DFO requires 8-to 12-hour infusions a minimum of five times per week. Deferiprone is administered in an oral daily regimen. Although pharmacologically efficacious, clinical effectiveness of ICT within the real-world setting is yet to be fully elucidated. A naturalistic cohort study of 60 patients (beta-thalassaemia, n=40; sickle cell disease, n=14; myelodysplastic syndromes, n=6; 63% female) receiving ICT in four UK treatment centres was conducted. Serum ferritin level data were abstracted from medical charts. Compliance, HRQOL, satisfaction and resource utilisation data were collected from interviews. Maximum ICT costs were estimated using the resource utilisation data associated with DFO. Mean serum ferritin levels, generally, remained elevated despite ICT. Compliance was suboptimal and HRQOL scores were lower than population norms. The total estimated mean weighted annual per-patient cost of DFO treatment was approximately pound19,000. DFO-related equipment, DFO drug, and home healthcare were estimated to account for 43%, 19% and 24% of costs, respectively. Other more minor components of total annual costs were for in-patient infusions, ICT home delivery services and monitoring costs. Generally, patients are not achieving target serum ferritin thresholds despite chronic treatment for iron overload. ICT appears to negatively impact HRQOL; compliance with ICT is poor; and, in the case of DFO, treatment costs well exceed the cost of DFO alone. These results suggest that current ICT in the real-world setting is suboptimal with respect to various clinical, HRQOL and economic outcomes.


Phage phi29 DNA replication organizer membrane protein p16.7 contains a coiled coil and a dimeric, homeodomain-related, functional domain.
The Bacillus subtilis phage varphi29-encoded membrane protein p16.7 is one of the few proteins known to be involved in prokaryotic membrane-associated DNA replication. Protein p16.7 contains an N-terminal transmembrane domain responsible for membrane localization. A soluble variant lacking the N-terminal membrane anchor, p16.7A, forms dimers in solution, binds to DNA, and has affinity for the varphi29 terminal protein. Here we show that the soluble N-terminal half of p16.7A can form a dimeric coiled coil. However, a second domain, located in the C-terminal half of the protein, has been characterized as being the main domain responsible for p16.7 dimerization. This 70-residue C-terminal domain, named p16.7C, also constitutes the functional part of the protein as it binds to DNA and terminal protein. Sequence alignments, secondary structure predictions, and spectroscopic analyses suggest that p16.7C is evolutionarily related to DNA binding homeodomains, present in many eukaryotic transcriptional regulator proteins. Based on the results, a structural model of p16.7 is presented.


Dispersion, aberration and deconvolution in multi-wavelength fluorescence images.
The wavelength dependence of the incoherent point spread function in a wide-field microscope was investigated experimentally. Dispersion in the sample and optics can lead to significant changes in the point spread function as wavelength is varied over the range commonly used in fluorescence microscopy. For a given sample, optical conditions can generally be optimized to produce a point spread function largely free of spherical aberration at a given wavelength. Unfortunately, deviations in wavelength from this value will result in spherically aberrated point spread functions. Therefore, when multiple fluorophores are used to localize different components in the same sample, the image of the distribution of at least one of the fluorophores will be spherically aberrated. This aberration causes a loss of intensity and resolution, thereby complicating the localization and analysis of multiple components in a multi-wavelength image. We show that optimal resolution can be restored to a spherically aberrated image by constrained, iterative deconvolution, as long as the spherical aberration in the point spread function used for deconvolution matches the aberration in the image reasonably well. The success of this method is essentially independent of the initial degree of spherical aberration in the image. Deconvolution of many biological images can be achieved by collecting a small library of spherically aberrated and unaberrated point spread functions, and then choosing a point spread function appropriate for deconvolving each image. The co-localization and relative intensities of multiple components can then be accurately studied in a multi-wavelength image.


Advanced techniques for MRI of atherosclerotic plaque.
This review examines the state of the art in vessel wall imaging by magnetic resonance imaging (MRI) with an emphasis on the biomechanical assessment of atherosclerotic plaque. Three areas of advanced techniques are discussed. First, alternative contrast mechanisms, including susceptibility, magnetization transfer, diffusion, and perfusion, are presented as to how they facilitate accurate determination of plaque constituents underlying biomechanics. Second, imaging technologies including hardware and sequences, are reviewed as to how they provide the resolution and signal-to-noise ratio necessary for determining plaque structure. Finally, techniques for combining MRI data into an overall assessment of plaque biomechanical properties, including wall shear stress and internal plaque strain, are presented. The paper closes with a discussion of the extent to which these techniques have been applied to different arteries commonly targeted by vessel wall MRI.


A multicomponent hemolytic system in the pathogenic amoeba Naegleria fowleri.
A hemolytic activity associated with postnuclear supernatant fractions of Naegleria fowleri has been partially characterized in an attempt to isolate cytolytic molecules that may participate in naeglerial cytopathogenicity. Hemolysis by naeglerial postnuclear supernatant fractions was sensitive to heat and trypsin hydrolysis, and was inhibited by divalent cations. The majority of the hemolytic activity was nonlatent and associated with a particle fraction sedimenting at 48,000 X g (maximum) for 1 h. This particle-associated hemolytic activity appears to be membrane associated, as high salt concentration, chelating agents, and pH extremes were ineffective in solubilizing the hemolytic activity, whereas treatment with 0.15% Zwittergent 3-12, a dipolar ionic detergent, results in 98% release of the sedimentable hemolysin. The sigmoidal nature of the progress curve of postnuclear supernatant hemolysis, as well as synergistic interactions between fractions of amoebal whole cell extracts, suggests that the hemolytic activity has a multicomponent nature, with at least two and possibly three components participating in the hemolytic event. The significance of these findings in the context of naeglerial cytopathogenicity is discussed.


Advances in upper airway diseases and allergen immunotherapy.
The purpose of this review is to highlight important articles on upper airway disease and immunotherapy that appeared in the Journal of Allergy and Clinical Immunology and elsewhere during 2005. In recent studies of tissue from patients with chronic hypertrophic eosinophilic sinusitis, increased leukotriene C4 synthase and 5-lipoxygenase activity and increased levels of cysteinyl leukotriene production were demonstrated that correlated with disease severity but not with whether the patient was aspirin sensitive. However, the cysteinyl leukotriene 1 receptor was increased in leukocytes in the sinus tissue only in those patients with aspirin sensitivity. Major basic protein, released by eosinophils into the mucus in the paranasal sinus lumen, was found to reach concentrations capable of damaging the sinus epithelium, predisposing to bacterial infections. Testing the hypothesis that chronic hypertrophic eosinophilic sinusitis represents a reaction to common fungi, a double-blind trial of intranasal instillation of amphotericin B was conducted. There were marginal but significant differences in favor of amphotericin B treatment for sinus mucosal thickening on the basis of computed tomography and the evidence of eosinophilic inflammation in the sinus mucus. The effectiveness of topical nasal corticosteroids for treatment of nasal polyps was confirmed in 2 large studies. Improvement in sleep quality and daytime drowsiness in patients with allergic rhinitis treated with nasal corticosteroids was reported to correlate with reduction in nasal obstruction. The statistical analysis behind studies that reported a decrease in asthma exacerbations with nasal corticosteroids or oral antihistamines has been questioned. It appears that the results of at least one of these studies are indeed too good to be true. Although caution is still indicated in administering immunotherapy to patients receiving beta-adrenergic blocking agents, the prohibition might not be absolute. A study in patients with Hymenoptera sensitivity given venom immunotherapy revealed no increase in serious adverse reactions to venom injections and no greater incidence of reactions to insect stings in those taking beta-blocking agents. Sublingual immunotherapy for 8 to 12 weeks in patients with hazelnut sensitivity significantly increased their tolerance to hazelnut in double-blind, placebo-controlled challenges while inducing increased IgG4 and IL-10 levels, indicating induction of regulatory T cells. There were a number of articles in the Journal of Allergy and Clinical Immunology in 2005 that addressed the entity of chronic hypertrophic eosinophilic sinusitis. In addition, an update of the "Practice parameters on sinusitis" was published. The major focus in allergen immunotherapy continues to be sublingual administration.


Uncontrolled occupational exposure to 1,1-dichloro-1-Fluoroethane (HCFC-141b) is associated with acute pulmonary toxicity.
The toxicity of 1,1-dichloro-1-fluoroethane (HCFC-141b), a hydrochlorofluorocarbon (HCFC), is low according to animal studies. However, pulmonary manifestations associated with acute HCFC exposure by inhalation have not been reported as yet in man. We evaluated the pulmonary effects of HCFC-141b inhalation, caused by an accident, in previously healthy individuals. The subjects in this study were 15 workers in whom unpleasant symptoms developed after inhaling HCFC-141b at work. Clinical manifestations, radiologic findings, and changes in pulmonary function and airway hyperresponsiveness (AHR) over time were assessed, and BAL fluid analyses findings for four subjects were compared with those of four healthy volunteers (control subjects). (1) Cough, shortness of breath, and malaise developed in most patients, but only two patients complained of a sore throat. (2) A high-resolution CT scan of the chest revealed bilateral diffuse ground-glass opacities that were predominant in upper lung zones. (3) The mean (+/- SD) FVC was 71.4 +/- 18.86% predicted, and the mean FEV(1)/FVC ratio was 92.9 +/- 4.25%. Eleven patients (73%) showed restrictive ventilatory impairments during the initial tests. FVC gradually improved, and the FEV(1)/FVC ratio gradually decreased with time. (4) AHR was observed in four subjects during the initial tests. (5) BAL fluid samples revealed significantly higher neutrophil counts than those in control subjects. Overexposure to HCFC-141b was associated with parenchymal lung injury that was characterized by ground-glass opacities, elevated BAL neutrophil counts, and restrictive ventilatory impairment. Restrictive impairments improved with time after exposure.


[Diagnostic value of multislice spiral CT and MRI in detection of tumor recurrence after liver transplantation for hepatocellular carcinoma].
To investigate the manifestation and diagnostic value of multislice spiral CT (MSCT) and MRI imaging in detection of tumor recurrence after liver transplantation for hepatocellular carcinoma (HCC). The clinical data of 161 consecutive HCC patients who underwent orthotopic liver transplantation were retrospectively reviewed. Twenty-nine HCC patients were classified by pTNM according to the "Pittsburgh criteria". MSCT and MRI findings of tumor recurrence after liver transplantation were evaluated retrospectively in 29 stage II-IVb HCC patients. The recurrence site and relapse interval between liver transplantation and recurrence were analyzed. Lung tumor recurrence were found in 21 cases, presented as cotton-like lesions in a diameter of 2 - 3 cm, with a clear margin and homogeneous density. Pleural tumor recurrence was detected in 4 cases. Liver tumor recurrence were found in 9 cases, which can be divided into four subtypes: multinodular in 4 cases, diffuse lesion in 2 cases, huge mass in 2 cases, and uninodular in 1 case. Two cases showed tumor thrombus in the inferior vena cava and portal vein. Lymph node tumor recurrence was found in 9 cases, presented as multiple nodules at hepatic hilum, lesser peritoneal sac, posterior mediastinum, retroperitoneum, or around pancreatic head, and accompanied with merging and necrosis in one case. Bone tumor recurrence were found as osteolytic destruction in 4 cases, and accompanied with adjacent soft-tissue mass in 2 cases. The recurrence sites of the 29 cases were as following: lung (21 cases, 72.4%), liver (9 cases, 31.0%), lymph nodes (9 cases, 31.0%), bone (4 cases, 13.8%) and other sites (3 cases, 10.3%). Lung tumor recurrence was found in all the 10 stage IVb patients with tumor recurrence after liver transplantation, significantly more frequent than that in stage IVa patients (P = 0.023). After liver transplantation, all 25 patients with stage III approximately IVb HCC developed recurrence within one year, but in the 4 cases with stage II HCC at one year later (P = 0.009). The results of our study show that in hepatocellular carcinoma patients after liver transplantation, the lung and pleura are the most frequent site of recurrence, followed by liver, lymph node and bone as the second and third sites. The Stage IVb hepatocellular carcinoma should be regarded as a contradiction for liver transplantation due to rapid recurrence. Tumor recurrence occurs later in stage II HCC than in stage III approximately IVb patients. MSCT and MRI are of significant importance in diagnosis and formulating operation plan in HCC patients with recurrence after liver transplantation.


A1298C methylenetetrahydrofolate reductase mutation and coronary artery disease: relationships with C677T polymorphism and homocysteine/folate metabolism.
5, 10-Methylenetetrahydrofolate reductase (MTHFR) is a crucial enzyme in homocysteine/methionine metabolism. The most-studied C677T polymorphism in the MTHFR gene results in a thermolabile variant with reduced activity, and is associated with increased levels of total plasma homocysteine, a risk factor for coronary artery disease. A new mutation in the MTHFR gene (A1298C) has also been reported to lower enzyme activity. Whether A1298C is a risk factor for coronary artery disease, separately or in combination with C677T, and/or relative to total plasma homocysteine and folate status, is unclear to date. We evaluated this hypothesis in 470 angiographically characterized subjects, 302 with coronary artery disease, and 168 with normal coronary arteries. The frequency of the 1298C allele was 0.33 and that of combined heterozygosity 0.315. No difference was found in the frequency of the genotypes or when analyzed for combined heterozygosity between patients with coronary artery disease and normals. Independent of folate status, the 1298C allele was not associated with increased total plasma homocysteine. No additional effect of A1298C on total plasma homocysteine was observed in 148 combined heterozygotes compared with 98 heterozygotes for the C677T alone. These findings do not support a major role for the A1298C mutation in homocysteine metabolism and emphasize the hypothesis that MTHFR genotypes may interfere with coronary artery disease risk only when an unbalanced nutritional status leads to raised total plasma homocysteine levels.


Universal function for the brilliance of undulator radiation considering the energy spread effect.
Angular and spatial profiles of undulator radiation have been investigated to derive a universal function that evaluates the brilliance of undulator radiation and takes into account the effects of electron beam emittance and energy spread. It has been found that the effects of energy spread on the angular divergence and source size can be expressed by simple analytic expressions, and a universal brilliance function has been derived by convolution with the electron beam distribution functions. Comparisons with numerical results have been carried out to show the validity and applicability of the universal function.


Clinical Significance of Probiotics for Children with Idiopathic Nephrotic Syndrome.
We previously reported that a decrease in butyrate-producing bacteria in the gut is a potential cause of regulatory T cell (Treg) abnormalities in children with idiopathic nephrotic syndrome (INS). Therefore, we hypothesized that administration of butyrate-producing bacteria might reduce INS relapse and the need for immunosuppressants in these patients. Twenty patients in remission from INS (median age 5.3 years, 15 boys) were enrolled in the study and assigned to receive either daily oral treatment with a preparation of 3 g Clostridium butyricum or no probiotic treatment. The number of relapses and requirement for immunosuppressive agents were compared between the two groups. In the probiotic treatment group, analyses of the gut microbiota and Treg measurements were also performed. Probiotic-treated patients experienced fewer INS relapses per year compared with non-probiotic-treated patients (p = 0.016). Further, administration of rituximab in the probiotic treatment group was significantly less frequent compared with the non-probiotic-treated group (p = 0.025). In the probiotic treatment group, analyses before and after probiotic treatment revealed the significant increases in the relative abundance of butyrate-producing bacteria (p = 0.017) and blood Treg counts (p = 0.0065). Thus, oral administration of butyrate-producing bacteria during INS remission may reduce the frequency of relapse and the need for immunosuppressive agents.


Hibberdia magna (Chrysophyceae): a promising freshwater fucoxanthin and polyunsaturated fatty acid producer.
Algae are prominent producers of carotenoids and polyunsaturated fatty acids which are greatly prized in the food and pharmaceutic industry. Fucoxanthin represents a notable high-value carotenoid produced exclusively by algae. Its benefits range far beyond just antioxidant activity and include cancer prevention, anti-diabetes, anti-obesity, and many other positive effects. Accordingly, large-scale microalgae cultivation to produce fucoxanthin and polyunsaturated fatty acids is still under intensive development in the commercial and academic sectors. Industrially exploitable strains are predominantly derived from marine species while comparable freshwater fucoxanthin producers have yet to be explored. In this study, we searched for freshwater fucoxanthin producers among photoautotrophic flagellates including members of the class Chrysophyceae. The initial screening turned our attention to the chrysophyte alga Hibberdia magna. We performed a comprehensive cultivation experiments using a temperature × light cross-gradient to assess the impact of these conditions on the target compounds productivity. Here we present the observations that H. magna simultaneously produces fucoxanthin (max. 1.2% dry biomass) and polyunsaturated fatty acids (max. ~ 9.9% dry biomass) and is accessible to routine cultivation in lab-scale conditions. The highest biomass yields were 3.73 g L-1 accompanied by maximal volumetric productivity of 0.54 g L-1 d-1 which are comparable values to marine microalgae fucoxanthin producers in phototrophic mode. H. magna demonstrated different optimal conditions for biomass, fucoxanthin, and fatty acid accumulation. While maximal fucoxanthin productivities were obtained in dim light and moderate temperatures (23 °C× 80 µmol m-2 s-1), the highest PUFA and overall biomass productivities were found in low temperature and high light (17-20 °C × 320-480 µmol m-2 s-1). Thus, a smart biotechnology setup should be designed to fully utilize H. magna biotechnological potential. Our research brings pioneer insight into the biotechnology potential of freshwater autotrophic flagellates and highlights their ability to produce high-value compounds. Freshwater fucoxanthin-producing species are of special importance as the use of sea-water-based media may increase cultivation costs and prohibits inland microalgae production.


Crystal structure of N (1)-phenyl-N (4)-[(quinolin-2-yl)methyl-idene]benzene-1,4-di-amine.
In the title compound, C22H17N3, the dihedral angles between the central benzene ring and the terminal phenyl ring and quinoline ring system (r.m.s. deviation = 0.027 Å) are 44.72 (7) and 9.02 (4)°, respectively, and the bond-angle sum at the amine N atom is 359.9°. In the crystal, the N-H group is not involved in hydrogen bonding and the mol-ecules are linked by weak C-H⋯π inter-actions, generating [010] chains.


[The influence of the pulsed electrical stimulation on the morphology and the functions of the endothelial cells].
The aim of this study is to explore the effects of the pulsed electrical stimulation (PES) on the morphology, the proliferation and the values of NO and ET-1 of the endothelial cells (ECs). We chose the different frequency PES (1, 5, 10, 20, 50, 100 Hz) with 25 mV to stimulate the ECs for 6 hours. We observed the cell's morphous by the scanning electron microscope (SEM) and detected the values of MTT, NO and ET-1. The proliferation of the ECs was obviously rose up under the PES from 10 to 100 Hz. But the PES inhibited the proliferation with the frequency lower than 10 Hz. After stimulated with PES (20 - 100 Hz), the NO expression of ECs were increased obviously, and the peak value was appeared at 50 Hz. The peak value of ET-1 was appeared at 100 Hz. The PES has significant effects on the ECs' morphology, proliferation and expression of NO and ET-1. Particularly, the 50 Hz PES plays a positive role to enhance the ECs' function and to maintain the vascular biology.


[Advances in the research of effects of regulation of cell autophagy on wound healing].
As one of the self-protection mechanism, autophagy widely exists in eukaryotic cells. It plays an important role in maintaining cells survival, update, material recycling, and tissue homeostasis. A series of researches discovered that autophagy played dual function in fibrotic diseases. The induction of autophagy can promote the degradation of collagen on one hand, on the other hand, the regulation of autophagy through microRNA, transforming growth factor β, and other factors can promote the occurrence of fibrosis. In wound healing, autophagy may participate in the pathophysiological processes of inflammation, reepithlialization, and wound remodeling. The regulation of cell autophagy may become an effective way and the new target for treatment of wound and pathological scar.


Isolation, characterization, and molecular cloning of a specific Mycobacterium tuberculosis antigen gene: identification of a species-specific sequence.
A rabbit polyclonal antiserum exhibiting a specific recognition pattern for Mycobacterium tuberculosis proteins was used to screen an M. tuberculosis genomic library constructed in the expression vector lambda gt11. One clone, denominated C1:10, expressed M. tuberculosis-specific determinants as part of a large fusion protein with beta-galactosidase. The gene for this protein has been sequenced, and it encodes a protein of 134 amino acids (13.8 kDa) which did not display significant homology with any of the previously reported proteins in the data bases. Hybridization studies with restriction fragments of the cloned sequence revealed that it was not present in the genomes of related mycobacteria, namely, M. bovis, M. bovis BCG, M. flavescens, M. fortuitum, M. phlei, and M. vaccae. These findings suggest that we have detected a gene, or a fragment therefrom, unique for M. tuberculosis whose nucleotide and amino acid sequences could be useful tools in the design of an improved vaccine or a diagnostic method of greater accuracy for tuberculosis.


Influence of Pregnancy in Multiple Sclerosis and Impact of Disease-Modifying Therapies.
Purpose of this Review: This article is a systematic review on the influence pregnancy has on multiple sclerosis and the resulting impact of disease-modifying therapies. Findings: Multiple sclerosis predominantly affects young women with a clinical onset most often during the child-bearing age. The impact of multiple sclerosis and disease-modifying therapies on fertility, pregnancy, fetal outcome, and breastfeeding is a pivotal topic when it comes to clinical practice. The introduction of disease-modifying therapies has changed not only the natural history of the disease but also the perspective of pregnancy in women with multiple sclerosis. Family planning requires careful consideration, especially because many disease-modifying drugs are contraindicated during pregnancy. In this article, we review current evidence collected from published literature and drug-specific pregnancy registers on the use of disease-modifying therapies. Additionally, we discuss safety profiles for each drug and correlate them to both risk for the exposed fetus and risk for the mothers interrupting treatments when seeking pregnancy.


A development-specific protein in Myxococcus xanthus is associated with the extracellular fibrils.
We have been using monoclonal antibodies (MAbs) as probes to study developmentally relevant cell surface antigens (CSA) that may be required for cellular interactions in Myxococcus xanthus. Three independently isolated MAbs, G69, G357, and G645, isolated by Gill and Dworkin recognize a CSA detectable only on developing cells (J. S. Gill and M. Dworkin, J. Bacteriol. 168:505-511, 1986). The CSA is made within the first 30 min of submerged development and increases until myxosporulation. The CSA is also produced at low levels after 24 h in shaken-starved cultures and during glycerol sporulation. No antigen can be detected in lysed, vegetative cells, and expression of the antigen is blocked in the presence of rifampin or chloramphenicol. The antigen is expressed in submerged, developmental cultures of asg, bsg, csg, dsg, and mgl mutants and is not expressed in a dsp mutant. All of the three MAbs immunoprecipitate the same protein of approximately 97,000 Da from lysed developmental cells. Competitive immunoprecipitations suggest that they recognize at least two different epitopes on the CSA. The epitopes recognized by MAbs G69, G357, and G645 are sensitive to protease digestion, whereas the epitopes recognized by MAbs G357 and G645 are resistant to periodate oxidation. The epitope recognized by MAb G69 is sensitive to periodate oxidation. Fractionation of lysed developing cells shows that most of the antigen is localized in the pellet after centrifugation at 100,000 x g. To determine whether the antigen is expressed on the cell surface, we labeled developing whole cells with either MAb G69, G357, or G645 and gold-labeled anti-mouse immunoglobulin G. Low-voltage scanning electron microscopy of labeled cells shows that the antigen is associated with the fibrillar matrix that surrounds the cells and that the antigen is retained on isolated, developmental fibrils from M. xanthus. The CSA has been designated dFA-1, for developmental fibrillar antigen 1.


The role of the cholinergic pathway in growth hormone feedback.
Cholinergic pathways play an important role in the regulation of GH secretion. To assess their participation in GH feedback, we investigated the effect of pyridostigmine (an acetylcholinesterase inhibitor) on plasma GH responses to GH-releasing hormone (GHRH) plus TRH, insulin hypoglycemia, and arginine as well as on the inhibition of these responses by exogenous GH. The GH response to each stimulus was inhibited by an infusion of GH (0.55 micrograms/m2/min), started 4 h earlier. Pyridostigmine (120 mg, orally), administered 30 min before the stimulus, enhanced GH responses to GHRH and insulin during both saline and GH infusions. However, GH responses during combined administration of pyridostigmine and GH were less than those during pyridostigmine alone. GH responses to arginine, in contrast, were not affected by pyridostigmine in either the absence or presence of exogenous GH. TSH responses to TRH were unaltered by either GH or pyridostigmine. Pyridostigmine enhancement of GH responses to a maximally stimulatory dose of GHRH suggests that its effect is exerted by inhibition of somatostatin release. The lack of effect of pyridostigmine on plasma GH responses to arginine suggests that arginine and pyridostigmine increase GH secretion through a common pathway. The enhancement by pyridostigmine of GH responses in both the presence and absence of exogenous GH suggests that exogenous GH and pyridostigmine exert their discordant effects on GH secretion through independent mechanisms.


Iatrogenic diarrhea caused by sorbitol.
A case of severe diarrhea with devastating effects in a young patient with a head injury is reported. The cause was found to be sorbitol used as an inactive ingredient in a commonly prescribed medication. Sorbitol is present in many prescription and over-the-counter medications and should be considered in the differential diagnosis of patients who present with abdominal complaints.


[The royal philanthropic expedition of the vaccine (Xavier de Balmis/Josep Salvany). 1803-1806].
Six years after Jenner discovered the anti-smallpox vaccine, King Charles IV mandated the initiation of vaccination campaigns throughout his kingdom. The overseas campaign was coordinated by the Valencian military doctor Xavier de Balmis with the aid of the Catalan Josep Salvany. The vaccine was transported to America "in vivo" in 22 children. The expedition departed from La Coruña on November 1806 and arrived to the Venezuelan port of La Guayra where it was split in two: One sub expedition under the order of Josep Salvany, continued by land to Colombia, Ecuador, Peru and Bolivia. Salvany died in the Bolivian city of Cochabamba. The other sub expedition, leaded by Balmis himself, continued by sea to Cuba and Mexico. From Acapulco it arrived to Manila and from there to Macau followed by inland penetration into China.


Novel gonadotropin-releasing hormone antagonists: peptides incorporating modified N omega-cyanoguanidino moieties.
In order to minimize the deleterious effects of histamine release resulting from the administration to rats and humans of some potent gonadotropin-releasing hormone (GnRH) antagonists, various arginine residues were replaced with the less basic N omega-cyano-N omega-alkyl- or -arylhomoarginine, -arginine, or -p-aminophenylalanine and N omega-triazolyllysine, -ornithine or -p-aminophenylalanine residues in active analogues. These novel analogues were synthesized on a solid-phase support via a two-step modification of the N omega-NH2 of lysine, ornithine, or p-aminophenylalanine residues in otherwise protected resin bound peptides. Most analogues were tested in the rat antiovulatory assay (AOA) and three in vitro assays; a pituitary cell culture assay, a binding assay to pituitary cell membranes, and a histamine release assay. Introduction of the cyanoguanidino and N omega-triazolyl moieties into GnRH analogues yielded several water-soluble antagonists which showed a desirable therapeutic ratio (low histamine release activity to high in vivo potency). Among them, "Azaline" (10, [Ac-DNal1,DCpa2,DPal3,Lys5(atz), DLys6(atz),ILys8,DAla10]GnRH), inhibited ovulation in the rat by 90% at 2 micrograms/rat with an ED50 in the in vitro histamine release assay comparable to that of GnRH itself.


Fluctuating bond model of DNA gel electrophoresis.
We present a Monte Carlo algorithm that allows a small length scale numerical study of DNA gel electrophoresis in high electric fields, similar to the fluctuating bond model for dynamical properties of polymeric systems. This approach combines advantages of lattice Monte Carlo methods with those from continuous Brownian dynamics algorithms, and also takes into account the persistence length of DNA, as well as the random nature of the gel. The initial orientation and acceleration of a random-walk DNA conformation shows a number of features that can be related to experimental results. The detailed description of DNA motion provided by this approach may lead to a first realistic computer study of the process of DNA sequencing.


Reliability of the Community Balance and Mobility Scale (CB&M) in high-functioning school-aged children and adolescents who have an acquired brain injury.
To examine inter-rater, intra-rater and test-re-test reliability of the Community Balance and Mobility Scale (CB&M) and compare reliability in live vs videotape rating contexts for children with acquired brain injury (ABI). Repeated measures design. Seven physiotherapists (PTs) were trained as assessors. The primary assessor administered and scored baseline CB&M while the second assessor observed and scored independently (inter-rater reliability). Re-assessment occurred 3-10 days later by primary assessor (test-re-test reliability). Assessments were videotaped. There were 32 participants with ABI (mean age = 14 years 1 month (SD = 2 years 1 month)). Baseline mean scores were 67.4% (18.2) and 66.7% (18.3) for primary and second assessor, respectively. Primary assessors' re-test mean score was 69.3%. Inter-rater reliability ICC was 0.93 (95% confidence interval (CI) = 0.87-0.97). Test-re-test ICC was 0.90 (95%CI = 0.81-0.95) and Bland-Altman plot indicated greatest test-re-test differences for mid-range CB&M scores. Minimum detectable change (MDC₉₀) was 13.5% points. The CB&M showed excellent reliability in youth. Reliability was comparable for live and videotape rating approaches, meaning that the easier and less expensive live-rating can be recommended. Future work should focus on evaluation of responsiveness to change in rehabilitation centre and community intervention contexts.


Klotho, PTSD, and advanced epigenetic age in cortical tissue.
This study examined the klotho (KL) longevity gene polymorphism rs9315202 and psychopathology, including posttraumatic stress disorder (PTSD), depression, and alcohol-use disorders, in association with advanced epigenetic age in three postmortem cortical tissue regions: dorsolateral and ventromedial prefrontal cortices and motor cortex. Using data from the VA National PTSD Brain Bank (n = 117), we found that rs9315202 interacted with PTSD to predict advanced epigenetic age in motor cortex among the subset of relatively older (>=45 years), white non-Hispanic decedents (corrected p = 0.014, n = 42). An evaluation of 211 additional common KL variants revealed that only variants in linkage disequilibrium with rs9315202 showed similarly high levels of significance. Alcohol abuse was nominally associated with advanced epigenetic age in motor cortex (p = 0.039, n = 114). The rs9315202 SNP interacted with PTSD to predict decreased KL expression via DNAm age residuals in motor cortex among older white non-Hispanics decedents (indirect β = -0.198, p = 0.027). Finally, in dual-luciferase enhancer reporter system experiments, we found that inserting the minor allele of rs9315202 in a human kidney cell line HK-2 genomic DNA resulted in a change in KL transcriptional activities, likely operating via long noncoding RNA in this region. This was the first study to examine multiple forms of psychopathology in association with advanced DNA methylation age across several brain regions, to extend work concerning the association between rs9315202 and advanced epigenetic to brain tissue, and to identify the effects of rs9315202 on KL gene expression. KL augmentation holds promise as a therapeutic intervention to slow the pace of cellular aging, disease onset, and neuropathology, particularly in older, stressed populations.


Contribution of forebrain noradrenaline innervation to the central circulatory effects of alpha-methyldopa and 6-hydroxydopamine.
We studied the circulatory effects of chronic lesions of the ascending noradrenergic (NA) projections to the forebrain on the acute effects of intracisternal (i.c.) alpha-methyldopa (alpha-MD) and 6-hydroxydopamine (6-OHDA) on mean arterial pressure (MAP) and heart rate (HR) in conscious rabbits with arterial baroreceptors either intact or denervated (sinoaortic denervation, SAD). Both drugs acutely release neurotransmitter from central NA neurons. I.c. 6-OHDA produced acute hypertension and bradycardia while i.c. alpha-MD produced acute hypotension and bradycardia. The responses are qualitatively similar in SAD rabbits except that after 6-OHDA, HR increased. In another group we studied the effects of the drugs 3-4 weeks after localised injections of 6-OHDA in the midbrain dorsal and ventral NA bundles. Local 6-OHDA depleted forebrain regions of NA by 44-76%, and had no effects on basal values of MAP or HR. The pressor and depressor effects, of 6-OHDA and alpha-MD respectively, were little affected by the lesions in either intact or SAD rabbits. By contrast, in rabbits with intact baroreceptors, the lesion abolished the bradycardia produced by i.c. alpha-MD and 6-OHDA. The latter drug now produced a late tachycardia. In SAD rabbits, however, there was no effect on the alpha-MD-induced bradycardia, but the 6-OHDA tachycardia was enhanced. Since the major effects of the lesions were confined to the rabbits with intact baroreceptor afferents, it suggests that the ascending NA pathways are important for the cardiac responses dependent on baroreceptor input. In intact animals, both drugs produce bradycardia through facilitation of the vagal component of the baroreceptor-heart rate reflex. In SAD rabbits, almost all the changes to HR are mediated through the cardiac sympathetic and the lesions have little effect on HR.


Differential expression and clinical significance of COX6C in human diseases.
Mitochondria, independent double-membrane organelles, are intracellular power plants that feed most eukaryotic cells with the ATP produced via the oxidative phosphorylation (OXPHOS). Consistently, cytochrome c oxidase (COX) catalyzes the electron transfer chain's final step. Electrons are transferred from reduced cytochrome c to molecular oxygen and play an indispensable role in oxidative phosphorylation of cells. Cytochrome c oxidase subunit 6c (COX6C) is encoded by the nuclear genome in the ribosome after translation and is transported to mitochondria via different pathways, and eventually forms the COX complex. In recent years, many studies have shown the abnormal level of COX6C in familial hypercholesterolemia, chronic kidney disease, diabetes, breast cancer, prostate cancer, uterine leiomyoma, follicular thyroid cancer, melanoma tissues, and other conditions. Its underlying mechanism may be related to the cellular oxidative phosphorylation pathway in tissue injury disease. Here reviews the varied function of COX6C in non-tumor and tumor diseases.


Fusarium endophthalmitis following keratitis associated with contact lenses.
A recent outbreak of fungal keratitis associated with contact lens use has been reported. During the past 4 months, a total of 36 patients with Fusarium keratitis have presented to one medical center. Two cases of Fusarium endophthalmitis resulting from this series of fungal keratitis associated with soft contact lens wear are described.


[Inflammatory syndrome, anicteric cholestasis and hepatic adenoma].
An unusual form of adenoma of left lobe of liver was detected fortuitously in a young woman with an inflammatory syndrome and an anicteric cholestasis. In this case, a positive correlation existed between the adenoma and the treatment with estrogens, the disappearance of the biologic anomalies after exeresis of the adenoma being suggestive of an increased production of fibrinogen by hepatocytes. The cholestasis was probably the result of pressure exerted by the adenoma. Excision of the adenoma was justified by the risk of hemorrhagic complications and the possibility of malignant changes in the tumor.


Living well with rheumatoid arthritis.
The overall aim of this study was to understand the occupational lives of people with rheumatoid arthritis. Further aims were to identify the creative agency that occurs while performing these occupations and to understand the socio-cultural aspects of engaging in valued occupations. Five participants were recruited and various qualitative methods of data collection were engaged, including open interviews, participant observation and gathering occupational diaries. A combination of thematic and narrative analysis was performed. Findings uncovered six themes, including; changing occupations; environmental factors count; taking control over occupations; being or becoming normal; people and objects are important; hopes and dreams matter. Subthemes uncovered how individuals constantly adapt and alter their occupations; some radically changing lifestyles for the better, while others work towards regaining occupational control. Meaning of occupations became apparent. People were creative agents. Work and leisure occupations featured strongly. Objects and other individuals were significant factors to individuals when engaging in occupations. People strived to be 'normal' in their occupational worlds. The implication of these results in relation to professional practice for therapists is that attention should be refocused on the occupational narratives of clients, working with the positive, creative aspects that people are already employing and building on these in areas that might not been seen as traditional, such as work and leisure.


Injectable hyaluronic acid and platelet lysate-derived granular hydrogels for biomedical applications.
Towards the repair of damaged tissues, numerous scaffolds have been fabricated to recreate the complex extracellular matrix (ECM) environment to support desired cell behaviors; however, it is often challenging to design scaffolds with the requisite cell-anchorage sites, mechanical stability, and tailorable physicochemical properties necessary for many applications. To address this and to improve on the properties of hyaluronic acid (HA) hydrogels, we combined photocrosslinkable norbornene-modified HA (NorHA) with human platelet lysate (PL). These PL-NorHA hybrid hydrogels supported the adhesion of cells when compared to NorHA hydrogels without PL, exhibited tailorable physicochemical properties based on the concentration of individual components, and released proteins over time. Using microfluidic techniques with on-chip mixing of NorHA and PL and subsequent photocrosslinking, spherical PL-NorHA microgels with a hierarchical fibrillar network were fabricated that exhibited the sustained delivery of PL proteins. Microgels could be jammed into granular hydrogels that exhibited shear-thinning and self-healing properties, enabling ejection from syringes and the fabrication of stable 3D constructs with 3D printing. Again, the inclusion of PL enhanced cellular interactions with the microgel structures. Overall, the combination of biomolecules and fibrin self-assembly arising from the enriched milieu of PL-derived proteins improved the bioactivity of HA-based hydrogels, enabling the formation of dynamic systems with modular design. The granular systems can be engineered to meet the complex demands of functional tissue repair using versatile processing techniques, such as with 3D printing.