Novel therapies in lupus - focus on nephritis.
Lupus nephritis (LN) is one of the major complications of Systemic Lupus Erythematosus (SLE) and its treatment remains a challenge. Although the classical and widely used immunosuppressive agents have accounted for a significant improvement in the survival and decreased the progression to end-stage renal failure they lack selectivity for the underlying immune dysregulation. In addition the toxicity related to their use and the relapses after treatment are of major concern not least because of the adverse effect on the prognosis of the patients with SLE who have kidney involvement. The development of more specific pharmacological agents for patients with SLE is still a major research goal. Ideally these agents should provide a better long-term prognosis for SLE patients and be less toxic. In this review we summarise the mechanism of action and the results obtained with a variety of drugs that have recently been utilized in the treatment of patients with lupus especially those with nephritis. We discuss the clinical usefulness of B- -cell depletion principally anti-CD20 antibodies blockage of co-stimulatory pathways (anti-CD40 ligand antibody CTLA4Ig) the induction of immune tolerance (LJP 394 peptide specific vaccination) and therapy targeting cytokines (anti-IL10 antibody BLyS blockage) and the complement system (anti-C5 antibody). Immunoablative doses of Cyclophosphamide (CyC) with or without Haematopoietic Stem Cell Transplantation (HSCT) and the possibilities of gene therapy are also reviewed. The use of intravenous immunoglobulin (IVIg) and plasmapheresis are not discussed because these treatments have been used in clinical practice for several years.


Serum uric acid and ambulatory blood pressure in children with primary hypertension.
Hyperuricemia is associated with primary hypertension (HTN) in adults and children. Furthermore, uric acid levels during childhood are associated with blood pressure (BP) levels in adulthood. We measured 24-h ambulatory BP and serum uric acid (SUA) in 104 children referred for possible hypertension. Mean age was 13.7 +/- 2.6 y (range, 7-18 y) with 67 males and 37 females; 74 were African-American, 29 Caucasian and one Asian. SUA was associated with age (r = 0.38, p = 0.0001) and BMI Z-score (r = 0.23, p = 0.021). SUA was significantly associated with mean ambulatory systolic (S) and diastolic (D) BP. Mean ambulatory BP was normalized to gender- and height-specific reference standards using BP index. SUA was significantly associated with 24-h DBP index and nocturnal DBP index after adjusting for age, gender, race, BMI Z-score and urinary sodium excretion. SUA was also significantly associated with 24-h DBP load and nocturnal DBP load. Uric acid was significantly associated with increased likelihood for diastolic HTN (OR = 2.1, CI = 1.2, 3.7; p = 0.0063) after adjusting for other co-variables. Among children at risk for HTN, the likelihood for diastolic HTN (as defined by ambulatory blood pressure monitoring) increases significantly as SUA increases. SUA may be associated with increased severity of HTN during youth.


Melatonin protects against myocardial doxorubicin toxicity in rats: role of physiological concentrations.
Doxorubicin (Dox) is a widely used antineoplastic drug. Oxygen radical-induced injury of membrane lipids is considered to be the most important factor responsible for the development of Dox-induced cardiotoxicity. The pineal secretory product, melatonin, is known to be a potent free radical scavenger and its pharmacological concentrations have been shown to reduce Dox-induced cardiac damage. However, the physiological role of melatonin in the prevention of this damage is unknown. We investigated physiological and pharmacological effects of melatonin on Dox-induced changes in the levels of malondialdehyde (MDA), a lipid peroxidation product, and morphological changes in heart. Rats were pinealectomized (Px) or sham-operated (control) 2 months before the studies. Melatonin was administered [4 mg/kg, intraperitoneally (i.p.)] 1 hr before or 24 hr after the administration of a single dose of Dox (20 mg/kg, i.p.) and continued for 2 days. The levels of MDA Dox was found to be significantly higher in the Px rats (55.9 +/- 0.6 nmol/g tissue) than intact control animals (42.6 +/- 0.4). Dox administration to Px and non-Px rats significantly increased the MDA levels. Pre- and post-treatment with melatonin in both Px and intact rats significantly reduced MDA levels. Morphological changes parallelled the MDA alterations. These findings strongly suggest that both physiological and pharmacological concentrations of melatonin are important in protecting the heart from Dox-induced damage in rats. It would seem valuable to test melatonin in clinical trials for prevention of possible heart damage associated with Dox.


Spiritual aspects of end-of-life care for Muslim patients: experiences from Iran.
The aim of this article is to describe the spiritual aspects of palliative care of Muslim patients based on experiences of end-of-life care in Iran. The religions of the world play a major part in the life cycle of their adherents, and most have rituals and beliefs concerning the care of dying people. For Muslims, death is believed to be not only the cessation of a complex set of biochemical processes, but also a belief that the spirit continues to live and dying is a passage from this world to the resurrection. The spirit is believed to be eternal and does not perish with death. According to Muslims' beliefs, reading of the Quran (the main religious text) can produce peace of mind in those who are near death. Nursing research has shown that the spiritual dimension of care infiltrates all aspects of nursing care. Palliative care nurses need to be informed about religious aspects of people around the world as a part of palliative care. This article indicates the methods of attending to spiritual care for Muslim patients based upon our experiences in Iran.


Hydroxycarbamine: from an Old Drug Used in Malignant Hemopathies to a Current Standard in Sickle Cell Disease.
While hydroxycarbamide (hydroxyurea, HU) has less and fewer indications in malignant hemopathies, it represents the only widely used drug which modifies sickle cell disease pathogenesis. Clinical experience with HU for patients with sickle cell disease has been accumulated over the past 25 years in Western countries. The review of the literature provides increasing support for safety and efficacy in both children and adults for reducing acute vaso-occlusive events including pain episodes and acute chest syndrome. No increased incidence of leukemia and teratogenicity was demonstrated. HU has become the standard-of-care for sickle cell anemia but remains underused. Barriers to its use should be identified and overcome.


Microbial pathogens associated with acute childhood diarrhoea in Kumasi, Ghana.
Diarrhoeal diseases are among the most frequent causes of morbidity and mortality in children worldwide, especially in sub-Saharan Africa. This case-control study was conducted to investigate the bacterial, viral and parasitic pathogens associated with acute diarrhoea among children attending three health facilities in Kumasi, Ghana. Stool specimens were collected from 240 children under 5 years of age visiting hospitals in Kumasi, Ghana due to acute diarrhoea and from 107 healthy controls of similar age. Both intestinal and malaria parasites were diagnosed by microscopy whereas rota- and adenoviruses were identified by stool antigen immunochromatograhic testing. Bacterial enteropathogens were detected by conventional culture techniques. Of all subjects, 23 (6.6%) were positive for malaria parasitaemia, 139 (40.1%) had at least one bacterial agent in their stool and 25 (7.2%) had ova or parasites. Subjects infected with malaria had the highest odds of having diarrhoea [12.0 (95% CI 1.56, 92.35)] followed by those with rotaviruses [4.4 (95% CI 2.05, 9.47)] and bacterial infection [4.99 (95% CI 1.45, 17.17)]. In conclusion, this study was unique as it looked at the three groups of pathogens (parasites, viruses and bacteria) that cause acute diarrhoea in children in the Kumasi metropolis of Ghana. This study has shown for the first time since 2004 that malaria parasitaemia, rotavirus and bacterial infections still remain common pathogens associated with acute childhood diarrhoea in the Kumasi metropolis of Ghana.


Increased circulating oxidised low-density lipoprotein and antibodies to oxidised low-density lipoprotein in preeclampsia.
Enhanced oxidative stress is involved in the pathogenesis of endothelial dysfunction in preeclampsia (PE). Circulating oxidised LDL (oxLDL) and antibodies to oxLDL (Ab-oxLDL) have been found to be associated with atherosclerosis. The objectives of this study were to investigate the association of oxLDL and Ab-oxLDL with PE and to assess the association between oxLDL and Ab-oxLDL. The levels of oxLDL and Ab-oxLDL were measured by enzyme-linked immunoassay in 78 women with preeclampsia (PE group) and 78 women with normal pregnancy (control group). The PE group had higher oxLDL and Ab-oxLDL levels than the control group (485.1vs.145.9 ng/ml, p < .001) and (578.7 vs 216.2 mU/ml, p < .001), respectively. However, Ab-oxLDL levels were not associated with the levels of oxLDL, age, BMI, gestational age, systolic blood pressure (SBP) and diastolic blood pressure (DBP) in both the groups. In conclusion, our study showed that PE was associated with increased oxLDL and Ab-oxLDL, which may reflect the enhanced oxidative stress in PE. Impact Statement Preeclampsia (PE) is a potentially life-threatening condition and both maternal and foetal complications can develop if it is not monitored appropriately. The pathogenesis of endothelial dysfunction in PE is related to the enhanced oxidative stress and oxidation of LDL. However, more studies were required as previous studies had not shown a consistent association of oxLDL and Ab-oxLDL with PE. Our study showed significant association of oxLDL and Ab-oxLDL with PE, indicating that their levels may be reliable indicators of oxidation stress and of the risk of PE. Levels of oxidative stress markers may have implications for clinical practice, such as their association with intrauterine growth restriction (IUGR), HELLP syndrome or eclampsia, foetal birth weight and premature delivery. Further research is still needed, ideally as a prospective cohort study to investigate the association of oxLDL and Ab-oxLDL with such outcome parameters.


Pentalogy of Cantrell: Is Echocardiography Sufficient in the Neonatal Period?
Pentalogy of Cantrell is a rare syndrome that is characterized by varying degrees of midline wall defects and congenital cardiac anomalies. A left ventricular diverticulum (LVD) is defined as partial ectopia cordis, can be part of the pentalogy of Cantrell, and can put the patient at risk of severe complications. Early diagnosis and ligation/resection of the LVD is important to prevent complications. We report on a case of pentalogy of Cantrell, in which a LVD was diagnosed only at 2 months of age despite preceding pre- and postnatal echocardiography. We conclude that in the suspicion of pentalogy of Cantrell, either complete or incomplete, cardiac magnetic resonance imaging should be performed, when possible, to avoid the potential complication of a herniating ventricular diverticulum.


Hypertrophic cardiomyopathy.
Hypertrophic cardiomyopathy is a diverse clinical and pathophysiologic disorder of unknown cause that principally involves the left ventricle and is manifested as asymmetric or concentric hypertrophy. If asymmetric, the hypertrophy is usually greatest in the ventricular septum, but variations occur in which the hypertrophy may be maximal at the mid-ventricular level, at the apex, or rarely, in the free wall of the left ventricle. Right ventricular involvement is usually less evident. The principal abnormality in systole is the obstruction to left ventricular outflow caused by systolic anterior motion (SAM) of the anterior or posterior mitral leaflet(s) with mitral leaflet-septal contact. SAM occurs as the result of the Venturi forces created by the rapid ejection of blood through an outflow tract that is narrowed by upper septal hypertrophy, drawing the mitral leaflet(s) anteriorly. The time of onset and duration of mitral leaflet-septal contact determine the magnitude of the pressure gradient. Mitral regurgitation invariably accompanies the obstruction to outflow. Ventriculomyectomy surgery, by thinning the septum and widening the outflow tract, abolishes the abnormal mitral leaflet motion and, consequently, the obstruction to outflow and the mitral regurgitation. In symptomatic patients with resting obstruction this form of surgery more dramatically relieves the systolic abnormalities and the accompanying symptoms than any form of medical therapy currently available. The extent of hypertrophy is believed to be the principal determinant of impaired left ventricular relaxation and increased chamber stiffness that characterize diastole in hypertrophic cardiomyopathy. Diastolic dysfunction is common to most such patients irrespective of the presence or absence of outflow obstruction. Calcium entry blockers may improve the left ventricular relaxation process and relieve symptoms in patients with hypertrophic cardiomyopathy, particularly the subgroup with no obstruction to outflow. Atrial and ventricular arrhythmias are responsible for a significant proportion of the morbidity and mortality, and their prevalence appears to depend on the presence of obstruction and the extent of hypertrophy. Thus, the major manifestations of hypertrophic cardiomyopathy in systole and diastole, as well as the disturbances in rhythm, appear to be related to the site and/or extent of the hypertrophic process. We have learned much about hypertrophic cardiomyopathy in the 30 years since its modern description. The vast majority of symptomatic patients can now be improved with specific medical or surgical therapy.(ABSTRACT TRUNCATED AT 400 WORDS)


Risk of prolapse and urinary complications in adult spina bifida patients with neurogenic acontractile detrusor using clean intermittent catheterization versus Valsalva voiding.
To assess the relative risks of pelvic organ prolapse (POP) and urinary complications in adult spina bifida patients with neurogenic acontractile detrusor voiding with Valsalva versus those using clean-intermittent catheterization (CIC). We conducted a retrospective analysis including all spina bifida patients with neurogenic acontractile detrusor with a minimum follow-up of 12 months. Patients were then divided in two groups according to their bladder management: voiding with Valsalva versus CIC. The primary endpoint was any de novo or worsened rectal and/or pelvic organ prolapse (POP) diagnosed during follow-up. The secondary outcome was urinary complications defined as febrile urinary tract infections (UTI) and/or urolithiasis and/or renal failure. Fifty-five patients (50.9% were males) met the inclusion/exclusion criteria: 28 voiding with Valsalva and 27 performing CIC. At baseline, the rates of vaginal prolapse (44.4% vs 50%; P = 0.99), and rectal prolapse/intussusception (25.9% vs 21.4%; P = 0.76) were similar in both groups. After a median follow-up of 80.6 and 65.6 months, respectively (P = 0.29), the rate of de novo or worsened rectal prolapse/intussusception was higher in the Valsalva voiding group than in the CIC group (32.1% vs 3.7%; P = 0.01). De novo or worsened vaginal prolapses were also more common in the Valsalva voiding group, but it did not reach statistical significance (33.3% vs 11.1%; P = 0.29). Valsalva voiding might be harmful in adult spina bifida patients with neurogenic acontractile detrusor as it may increase the risk of rectal prolapse/intussusception. Overall, the prevalence of POP and rectal prolapse was high in both groups.


Radiation-induced inflammation and autoimmune diseases.
Currently, ionizing radiation (IR) plays a key role in the agricultural and medical industry, while accidental exposure resulting from leakage of radioactive sources or radiological terrorism is a serious concern. Exposure to IR has various detrimental effects on normal tissues. Although an increased risk of carcinogenesis is the best-known long-term consequence of IR, evidence has shown that other diseases, particularly diseases related to inflammation, are common disorders among irradiated people. Autoimmune disorders are among the various types of immune diseases that have been investigated among exposed people. Thyroid diseases and diabetes are two autoimmune diseases potentially induced by IR. However, the precise mechanisms of IR-induced thyroid diseases and diabetes remain to be elucidated, and several studies have shown that chronic increased levels of inflammatory cytokines after exposure play a pivotal role. Thus, cytokines, including interleukin-1(IL-1), tumor necrosis factor (TNF-α) and interferon gamma (IFN-γ), play a key role in chronic oxidative damage following exposure to IR. Additionally, these cytokines change the secretion of insulin and thyroid-stimulating hormone(TSH). It is likely that the management of inflammation and oxidative damage is one of the best strategies for the amelioration of these diseases after a radiological or nuclear disaster. In the present study, we reviewed the evidence of radiation-induced diabetes and thyroid diseases, as well as the potential roles of inflammatory responses. In addition, we proposed that the mitigation of inflammatory and oxidative damage markers after exposure to IR may reduce the incidence of these diseases among individuals exposed to radiation.


Sensitivity, specificity and level of agreement of meat inspector detection of abnormal lymph nodes of farmed deer (Cervus elaphus) in New Zealand.
To assess the sensitivity (Se), specificity (Sp) and level of agreement in the detection of abnormal deer mesenteric lymph nodes (MLN) by official assessors (meat inspectors) for the purpose of slaughter premise surveillance for Johne's disease in New Zealand farmed deer. To determine Se and Sp, four meat inspectors in two commercial deer slaughter premises (DSP) each examined between 153 and 925 MLN under normal visual examination, palpation and/or incision inspection procedures. Abnormal MLN were independently defined as those with a circumference measurement of ≥ 55 mm and/or grossly visible pathological changes such as caseation, necrosis and/or mineralisation, while those with a circumference of <55 mm and without gross lesions were defined as normal. The inspectors' diagnosis of normal or abnormal was retrieved from the national DSP-based surveillance database for Johne's disease in deer. To determine between-inspector level of agreement, 54 meat inspectors visually examined two photographic images each of 19 normal and 10 abnormal MLN, and recorded their diagnosis. Between-inspector agreement was calculated based on a modification of Cohen's kappa statistic for multiple raters. The influence of covariates such as inspector age and experience on the between-inspector level of agreement were assessed using the Breslow-Day statistic and test for equal kappa coefficients. The weighted average Se and Sp of inspector detection of abnormal MLN was 13.3 (minimum 4.8, maximum 41.2)% and 99.9 (minimum 99.5, maximum 100.0)%, respectively. The level of between-inspector agreement in the diagnosis of abnormal and normal MLN was fair (κ = 0.32). Employment location, inspector age, experience inspecting deer or other species, and the number of shifts inspecting deer within the previous four weeks had no influence on between-inspector agreement (p > 0.10). Inspectors diagnosed abnormal deer MLN with a high specificity, but low sensitivity. These data supported that visual assessment of MLN characteristics was suitable for national surveillance for paratuberculosis, while highlighting the need for further emphasis on training of inspectors in abnormal lymph node detection.


[Association between methylenetetrahydrofolate reductase gene haplotypes and the susceptibility of chromosomal damage in coke-oven workers].
To investigate the association between MTHFR gene variances and chromosomal damage levels in peripheral blood lymphocyte in coke-oven workers exposed to polycyclic aromatic hydrocarbons (PAHs). One-hundred and forty coke-oven workers who exposed to a high level of PAHs and sixty-six non-exposed controls were selected as the study subjects. Chromosomal damage in peripheral lymphocyte was measured by the cytokinesis-block micronucleus (CBMN) assay. Urinary 1-hydroxypyrene (1-OHP) levels were measured as the internal dose of PAHs exposure. Two single nucleotide polymorphisms(SNPs) in MTHFR gene, including C677T, A1298C were detected by PCR-RFLP. The MTHFR haplotypes were estimated by Bayesian statistical method with the software of PHASE Version 2.1. The associations between haplotype pairs and CBMN were assessed by analysis of covariance in the coke-oven workers and controls. The variant allele frequencies for MTHFRC677T and A1298C were 0.56 and 0.16 respectively, which consistent with Hardy-Weinberg equilibrium. There was linkage disequilibrium between the two SNPs (D' = 0.99) in this study. Four haplotypes were calculated by PHASE, in terms of 677T - 1298A, 677C-1298A, 677C-1298C and 677T-1298C, the frequencies were 0.555,0.279,0.163 and 0.003 respectively. In coke-oven workers, the frequencies of total micronucleus of non-677C-1298A/677C-1298A haplotype pair was significantly higher than 677C-1298A/677C-1298A (1.00 +/- 0.67 vs 0.60 +/- 0.41, P = 0.04). The frequencies of total micronucleus of 677T-1298A/677T-1298A haplotype pair was significantly higher than 677C-1298A/677C-1298A (1.08 +/- 0.71 vs 0.60 +/- 0.41, P = 0.04). In coke-oven workers, the frequencies of total micronucleus among the different SNPs were not significant differences, either in the controls. The haplotypes of MTHFR gene might be one genetic susceptibility factors of PAH induced chromosomal damage in coke-oven workers.


The SMART personalised self-management system for congestive heart failure: results of a realist evaluation.
Technology has the potential to provide support for self-management to people with congestive heart failure (CHF). This paper describes the results of a realist evaluation of the SMART Personalised Self-Management System (PSMS) for CHF. The PSMS was used, at home, by seven people with CHF. Data describing system usage and usability as well as questionnaire and interview data were evaluated in terms of the context, mechanism and outcome hypotheses (CMOs) integral to realist evaluation. The CHF PSMS improved heart failure related knowledge in those with low levels of knowledge at baseline, through providing information and quizzes. Furthermore, participants perceived the self-regulatory aspects of the CHF PSMS as being useful in encouraging daily walking. The CMOs were revised to describe the context of use, and how this influences both the mechanisms and the outcomes. Participants with CHF engaged with the PSMS despite some technological problems. Some positive effects on knowledge were observed as well as the potential to assist with changing physical activity behaviour. Knowledge of CHF and physical activity behaviour change are important self-management targets for CHF, and this study provides evidence to direct the further development of a technology to support these targets.


A new murine monoclonal antibody for the diagnosis of erythroleukemia.
The authors have developed a murine monoclonal antibody, RC-82.4, against an antigen expressed by a human erythroleukemia cell line OCI-MIR. The antibody reacts with an antigen expressed by proerythroblasts, normoblasts, and some reticulocytes but not expressed in erythrocytes, granulocytes, monocytes, megakaryocytes, plasma cells, or lymphocytes. The authors have established an immunocytochemical method for studying bone marrow smears with RC-82.4. By studying bone marrow smears from 11 patients with M-6 erythroleukemia and 104 patients with various other hematologic and nonhematologic malignancies, the authors have found that RC-82.4 has great sensitivity and specificity in recognizing erythroid differentiation in blasts. The authors have used RC-82.4 and antihemoglobin antibodies to identify erythroblasts in acute and secondary acquired cases of erythroleukemia that would have been unclassifiable by morphologic and all other conventional cytochemical and immunocytochemical criteria.


Thioguanine, mercaptopurine: their analogs and nucleosides as antimetabolites.
6-Mercaptopurine (6MP) and 6-thioguanine (6TG) are analogs of the natural purines: hypoxanthine and guanine. Both mercaptopurine and thioguanine are substrates for hypoxanthine-guanine phosphoribosyltransferase and are converted into the ribonucleotides 6-thioguanosine monophosphate (6-thioGMP) and 6-thioinosine monophosphate (T-IMP) respectively. The accumulation of these monophosphates inhibits several vital metabolic reactions. Today, these thiopurine bases remain valuable agents for the induction and maintenance of remissions in patients with myelocytic and acute lymphocytic leukemia. Despite their proved clinical importance, 6MP and 6TG have certain therapeutic disadvantages, which have continued to stimulate the search for purine derivatives enhancing therapeutic efficacy. Considerable efforts have been made to prepare other novel mercaptopurine and thioguanine analogs and their nucleosides to improve the antitumor efficacy. The effectiveness of these thiopurines against certain tumor cell lines suggested that some of these mercaptopurine analogs and their nucleosides would be worthy of consideration in order to determine whether they exert a more selective effect against neoplastic cells than against normal cells or they might be useful in patients whose disease has become resistant to 6MP or 6TG. This review will focus on mercaptopurine analogs and their nucleosides as antimetabolite agents.


Identification of the State of Maximal Hyperemia in the Assessment of Coronary Fractional Flow Reserve Using Non-Invasive Electrical Velocimetry.
Previous research revealed that, in patients with coronary pressure-derived fractional flow reserve (FFR) in the 'grey zone' (0.75-0.85), repeated FFR assessments sometimes yield conflicting results. One of the causes of the fluctuations in FFR values around the grey zone may be imprecise identification of the point where maximal hyperemia is achieved. Identification of the state of maximal hyperemia during assessment of FFR can be challenging. This study aimed to determine whether non-invasive electrical velocimetry (EV) can be used to identify the state of maximal hyperemia.Stroke volume (SV), SV variation (SVV), and systemic vascular resistance index (SVRI) were determined by EV in 15 patients who underwent FFR assessment. Time intervals from initiation of adenosine infusion to achieving maximal hyperemia (timemFRR), as well as to achieving maximal cardiac output (CO), SV, SVV, and SVRI (timemCO, timemSV, timemSVV, and timemSVRI, respectively), were determined. TimemCO and timemSVV were closer to timemFRR than other values (timemSVV/timemFRR versus timemSVRI/timemFRR = 1.03 ± 0.2 versus 1.36 ± 0.4, P < 0.05). The maximum of SV was difficult to determine owing to considerable variations, but the maximum of SVV was clearly recognized. TimemCO and timemSVV were significantly correlated with timemFFR, with timemSVV showing a stronger correlation than timemSV (timemSVV: r = 0.92, P < 0.01; timemCO: r = 0.80, P < 0.01).Maximal SVV is reached close to maximal hyperemia. Monitoring of SVV with non-invasive EV during FFR assessment can help identify the state of maximal hyperemia.


Bimetal Metal-Organic Framework-Derived Ni-Mn@Carbon/Reduced Graphene Oxide as a Cathode for an Asymmetric Supercapacitor with High Energy Density.
As is known, metal-organic frameworks (MOFs) are a versatile class of materials in energy storage applications including supercapacitors. However, the individual kind of metal nodes connected by organic ligands to form a topological structure still limits the potential storage capacity of MOFs. Herein, a bimetal-based Ni-Mn MOF composite is configured with a one-pot hydrothermal method to derive a composite with a synergic effect to maximize the properties. Moreover, reduced graphene oxide (rGO) sheets are added as a conductive network to anchor the MOF-derived composite of Ni-Mn@C/rGO, which is expected to increase the conductivity of the materials system. The resulting composite exhibited a high specific capacitance of 1674 F g-1 at a current density of 0.3 A g-1, suggesting excellent energy storage performance. The composite was then integrated as the cathode in an asymmetrical supercapacitor with a 3D rGO aerogel anode, resulting in energy densities of 24.1 and 17.5 W h kg-1 at power densities of 88.9 and 444.4 W kg-1, respectively. Additionally, the device demonstrated remarkable long-term stability, with 90% capacitance retention after 10 000 charge-discharge cycles at 10 A g-1.


EFFECTS OF INTRAVENOUS DEXMEDETOMIDINE ON CARDIAC CHARACTERISTICS MEASURED USING RADIOGRAPHY AND ECHOCARDIOGRAPHY IN SIX HEALTHY DOGS.
Dexmedetomidine is a highly specific and selective α2-adrenergic receptor agonist widely used in dogs for sedation or analgesia. We hypothesized that dexmedetomidine may cause significant changes in radiographic and echocardiographic measurements. The objective of this prospective cross-sectional study was to test this hypothesis in a sample of six healthy dogs. Staff-owned dogs were recruited and received a single dose of dexmedetomidine 250 μg/m(2) intravenously. Thoracic radiography and echocardiography were performed 1 h before treatment, and repeated 10 and 30 min after treatment, respectively. One observer recorded cardiac measurements from radiographs and another observer recorded echocardiographic measurements. Vertebral heart score and cardiac size to thorax ratio on the ventrodorsal projection increased from 9.8 ± 0.6 v to 10.3 ± 0.7 v (P = 0.0007) and 0.61 ± 0.04 to 0.68 ± 0.03 (P = 0.0109), respectively. E point-to-septal separation and left ventricle internal diameter in diastole and systole increased from 2.4 ± 1.1 to 6.6 ± 1.9 mm, 32.3 ± 8.1 to 35.5 ± 8.8 mm, and 19.4 ± 6 to 27.0 ± 7.2 mm, respectively (P < 0.05). Fractional shortening and sphericity index decreased from 40.7 ± 5.8 to 24.4 ± 2.9%, and 1.81 ± 0.07 to 1.58 ± 0.04, respectively (P < 0.05). Moderate-to-severe mitral regurgitation and mild pulmonic regurgitation occurred in all dogs after dexmedetomidine administration. Findings indicated that dexmedetomidine could cause false-positive diagnoses of valvular regurgitation and cardiomegaly in dogs undergoing thoracic radiography and echocardiography.


Inhibition of platelet aggregation by cepharanthine is accomplished during the early, membrane-related activation process.
Cepharanthine, a biscoclaurine alkaloids which interact with biomembranes, has been found to inhibit platelet aggregation. The effects of this drug on morphological and physiochemical phenomena following collagen-induced platelet stimulation were investigated. In the presence of cepharanthine, stimulated platelets became spherical, but did not form pseudopoda , nor did they become aggregated. Physiochemical reactions such as accelerated oxygen consumption, release of membrane-bound Ca2+, release of Ca2+ into the extracellular medium and deporalization of the membrane potential were all inhibited by cepharanthine. Using D,L-dipalmitoyl phosphatidylcholine liposomes as the substrate, cepharanthine was shown to inhibit phospholipase A2 activity. These results suggest that the changes in the membrane following the interaction of collagen with its receptor are important for platelet activation. Cepharanthine may inhibits these membrane state changes, thus blocking all subsequent reactions.


High-speed atomic force microscope with a combined tip-sample scanning architecture.
A high-speed atomic force microscope (HS-AFM) based on a tip-sample combined scanning architecture is presented. In this system, the X-scanner, which is separated from the AFM head, carries the sample and scans along the fast-axis. The Y and Z scanners integrated in the AFM head oscillate an ultrashort cantilever probe and scan in the other two dimensions. The optical beam deflection method is improved to enable the laser to track the probe over a wide scan range. A novel probe holder realizes easy exchange and alignment of the probe. Due to the separation of the X and Y scanners, both appear with better dynamic performance and carrying capacity. Experiments show that the HS-AFM established in this work can achieve a line rate of up to 100 Hz with the basic proportional-integral-derivative control algorithm and linear driving. The permissible sample size and mass can be as large as several centimeters and above 40 g.


Multiple dens invaginatus affecting maxillary lateral incisors and a supernumerary tooth.
Dens invaginatus is a developmental variation resulting from an alteration in the normal growth pattern of the dental papilla of a tooth. This anomaly occurs predominantly in maxillary permanent lateral incisors. Multiple occurrence in maxillary incisor teeth in the same patient has frequently been reported, and examination of bilateral teeth for the anomaly is often carried out routinely. This paper reports an unusual case of multiple invaginations, including dens invaginatus affecting maxillary lateral incisors and a supernumerary tooth and minor invaginations of the upper canines. Moreover, the case illustrates the importance of examining all the teeth in patients who present with dens invaginatus and palatal pits in incisors and canines. The possibility that the supernumerary tooth had resulted from gemination of the lateral incisor tooth germ is discussed.


Effects of bromocriptine on prolactin release, electrical membrane properties and transmembrane Ca2+ fluxes in cultured rat pituitary adenoma cells.
The effects of the dopamine (DA) agonist bromocriptine on prolactin (Prl) release, electrical membrane properties and transmembrane Ca2+ fluxes have been studied in a clonal strain of rat pituitary adenoma cells (GH3). These cells generate Ca2+ dependent action potentials, and produce and secrete spontaneously both Prl and growth hormone. Prl release stimulated by thyroliberin (TRH) and elevated extracellular K+ concentration was completely blocked by bromocriptine, whereas the basal release was only moderately affected. The TRH and K+ evoked Prl release were half maximally inhibited by bromocriptine at 5-10 and 10-50 microM, respectively. The normal biphasic membrane response to TRH and the depolarizing effect of elevated K+ concentration were not altered by bromocriptine, whereas the Ca2+- spikes in Na+-free solution were suppressed by the drug. We therefore suggest that bromocriptine blocks the voltage sensitive Ca2+-channels of GH3 cell. In agreement with this notion, bromocriptine also suppressed the basal and TRH induced 45Ca2+ efflux from preloaded cells. We conclude that the inhibitory effect of bromocriptine on the voltage dependent Ca2+- channels is an important mechanism responsible for suppression of Prl release.


7-valent pneumococcal conjugate vaccine: new preparation. Prevents rare invasive infections in infants.
(1) Infants under two years of age are the children most exposed to invasive pneumococcal infections (meningitis and bacteraemia). The estimated incidence in France is about 45 cases per year per 100,000 in the first year of life. The 23-valent pneumococcal polysaccharide vaccine is ineffective in children under two years of age. (2) Marketing authorization has now been granted for a 7-valent pneumococcal conjugate vaccine for children under two years. It is the first pneumococcal vaccine specifically designed for this age group. (3) Its immunogenicity in 2 year old children has been carefully documented. (4) A comparative, randomised, double-blind trial involving nearly 38,000 Californian infants showed a lower incidence of both all invasive pneumococcal infections (approximately 1 case avoided per 400 children vaccinated), and those due to the 7 serotypes covered by the vaccine. (5) These results are not directly applicable to France, where the pneumococcal serotype distribution (especially the 7 serotypes covered by the vaccine) seems to be somewhat different, and where the incidence of invasive pneumococcal infections is much lower. (6) The 7-valent vaccine has not been assessed adequately in children who are at high risk for invasive pneumococcal infection. Some small studies of children with sickle-cell disease show adequate immunogenicity. (7) The known adverse effects of the 7-valent vaccine are acceptable, mainly comprising local reactions and fever. (8) The risk of an epidemiological shift towards serotypes not covered by the vaccine (through pharyngeal carriage and invasive infection) cannot been ruled out. In otitis media, an increase in pneumococcal infections due to serotypes not covered by the vaccine negates the benefit of vaccination. (9) In practice, considering the severity of invasive pneumococcal infections and the documented efficacy and safety of the 7-valent conjugate vaccine, vaccination is warranted for individual children under two years of age, especially those at risk, but epidemiological monitoring and pharmacovigilance must continue.


Repair of hypoplastic left heart syndrome of a 4.25-kg Jehovah's witness.
The care of patients who refuse homologous transfusions has challenged cardiac surgery teams to refine blood conservation techniques and question standard transfusion practices. We cared for a newborn child with hypoplastic left heart syndrome (HLHS) whose parents refused to give consent to care for the child that involved the transfusion of homologous blood. A Norwood Stage I procedure was planned with the understanding that transfusions would be avoided, if possible. A court order was obtained that specified the conditions under which the attending physicians would transfuse the newborn. The birth weight of the patient was 4.25 kg. A low prime cardiopulmonary bypass (CPB) circuit and aggressive blood conservation techniques that included modified ultrafiltration (MUF) allowed the completion of the repair and CPB portion of the operation without the use of blood. The lowest hematocrit during CPB was 20%. After an unsuccessful attempt to separate from CPB, blood was transfused. Recovery was consistent for HLHS patients following Norwood Stage I. However, at 1 month postoperatively, the patient did require a shunt reduction for pulmonary overcirculation. Norwood Stage II repair was completed at age 4 months without donor blood. The key to a successful outcome is a well-thoughtout plan by the surgeon, anesthesiologist and perfusionist. This plan should include careful monitoring of the patient's oxygenation and cardiovascular status.


[Bisphosphonates and maxillo-mandibular osteo(chemo)necrosis].
Maxillo-mandibular osteonecrosis is exceptional outside a context of cervico-facial radiotherapy. Bisphosphonates are non-metabolized pyrophosphate analogues which inhibit osteoclastic activity. Bisphosphonates are prescribed for the treatment of malignant hypercalcemia, osteolysis associated with metastatic bone disease, Paget's disease and osteoporosis. Maxillomandibular osteonecrosis with bisphosphonates can be observed in 1/10000 patients, but is probably underestimated due to lack of dental examination. We describe six cases of mandibular necrosis associated with bisphosphonates: five of them as part of their treatment regimen for a neoplastic condition and one for osteoporosis. Two patients developed spontaneous bone necrosis. In two others, tooth extraction preceded the onset of osteonecrosis. In the last two patients, we noted a preexisting dental infection. All the histopathological examinations showed necrotic bone colonized by Actinomyces. Bisphosphonate-induced osteonecrosis is only found in the maxillomandibular area because the jaws are the only bone in the skeleton exposed to the external environment. The mandible is rendered particularly prone to necrosis even after minor trauma because of its terminal vascularization. Careful oral examination is recommended before prescribing bisphosphonate therapy.


Stability and Stabilization of T-S Fuzzy Systems With Time-Varying Delays via Delay-Product-Type Functional Method.
This paper is concerned with the stability and stabilization problems of T-S fuzzy systems with time-varying delays. The purpose is to develop a new state-feedback controller design method with less conservatism. First, a novel Lyapunov-Krasovskii functional is constructed by combining delay-product-type functional method together with the state vector augmentation. By utilizing Wirtinger-based integral inequality and an extended reciprocally convex matrix inequality, a less conservative delay-dependent stability condition is developed. Then, the corresponding controller design method for the closed-loop delayed fuzzy system is derived based on parallel distributed compensation scheme. Finally, two classic numerical examples are given to show the effectiveness and merits of the proposed approaches.


The history of nonsurgical enteral tube feeding access.
Specialized nutrition support, particularly enteral feeding, has been used for centuries. Technologic advancements have affected the provision of enteral feeding. Feeding solutions and devices, as well as the techniques to place the feeding devices, have evolved. This article reviews the history of bedside placement methods for short-term enteral access devices.


Histochemical and ultrastructural criteria for early differentiation of human subcutaneous adipocytes.
The histochemical, enzyme-histochemical and ultrastructural characteristics of the adipocyte precursors in human embryos at 6-12 weeks of gestation were studied. Some consequent stages in the histogenesis and differentiation of the fat cells were maintained according to: 1/number and size of the lipid droplets; 2/position of the nucleus. The cells become rounder, accumulate lipid inclusions, acquire eccentric nucleus, gradually gather in clusters. No typical unilocular adipocytes were seen at this stage of fetal development. The enzyme-histochemistry disclosed that the reactions for glucose-6P-dehydrogenase, NADH2 diaphorase and especially lipoprotein lipase were highly expressed. Ultrastructurally the adipocyte precursors were with a great amount of organelles/mitochondria of typical sight, well developed rough and smooth endoplasmatic reticulum/, lipid droplets and glycogen which express their high functional activity. This study could provide criteria for understanding the processes of lipidogenesis and differentiation.


Suprathreshold stochastic resonance and noise-enhanced Fisher information in arrays of threshold devices.
We analyze the parametric estimation that can be performed on a signal buried in noise based on the parsimonious representation provided by a parallel array of threshold devices. The Fisher information contained in the array output about the input parameter is used as the measure of performance in the estimation task. For estimation on a suprathreshold input signal, we establish that enhancement of the Fisher information can be obtained by addition of independent noises to the thresholds in the array. Similar improvement by noise is also shown to be possible for the estimation error of the maximum likelihood estimator. These results extend the applicability of the recently introduced nonlinear phenomenon of suprathreshold stochastic resonance.


Discordant hemodynamic and fibrinolytic adaptations following a 6-week cardiac rehabilitation program.
The present study evaluated changes in hemodynamics and fibrinolysis during 6 weeks of participation in an exercise-based cardiac rehabilitation program. Fourteen patients trained for 3 days per week for 6 weeks using American College of Sports Medicine guidelines for intensity and duration. Blood samples were taken at baseline and after 3 and 6 weeks of participation and analyzed for tissue plasminogen activator (t-PA) activity and antigen, plasminogen activator inhibitor-1 (PAI-1) activity and antigen, and relative quantification of t-PA and PAI-1 RNA. Data were analyzed using repeated measures analysis of variance. Training elicited significant decreases in submaximal exercise heart rate and systolic blood pressure and resting systolic blood pressure (p<.05). There were no significant changes in plasma concentrations of t-PA or PAI-1, and no change was observed in t-PA or PAI-1 gene expression. The present findings suggest that favorable hemodynamic adaptations may occur after only 6 weeks of exercise-based cardiac rehabilitation, but longer training periods may be needed to elicit positive hemostatic adaptations.


[Congenital heart block and autoantibodies].
Maternal IgG autoantibodies against Ro52 (part of the anti-SSA specificity) are correlated with congenital heart block (CHB). Most cases revert spontaneously and can be monitored by Doppler echocardiography, but fetuses that progress into second-degree block require treatment with, e.g., corticosteroids. A third-degree block is irreversible and necessitates lifelong pacemaking. It may prove beneficial to screen all expectant mothers for anti-Ro52 autoantibodies. Decisions about this will require further studies of the diagnostic performance of the Ro52 autoantibody test.


Improving Asthma Care by Building Statewide Quality Improvement Infrastructure.
Pediatric medical professionals have an increasing desire for quality improvement (QI) methods that produce sustainable changes in health care delivery. Previous reports have described QI in single settings or single coordinating entities that work with multiple sites. The objectives of this project are (1) to improve care for children with asthma across multiple practice settings and (2) to develop state-level expertise to support QI projects across entities in multiple states. Using a multiwave approach, the Chapter Quality Network of the American Academy of Pediatrics implemented statewide learning collaboratives in several states. For each cycle, a national leadership team coached multiple American Academy of Pediatrics chapter leadership teams, which, in turn, coached individual pediatric practices through 2 nested learning collaboratives. State chapters received data and reporting tools and a curriculum fostering QI learning and support change at the practice level. Practices implemented an asthma assessment tool and registry, analyzed work flows, and implemented self-management tools in plan-do-study-act cycles. Sixteen process and outcome measures, including optimal asthma care, were collected and analyzed by using run charts on a monthly dashboard. Chapter leaders provided feedback on sustainable QI change through surveys and interviews. Optimal asthma care improved from 42% to 81% across the 4 waves. The percentage of patients rated by physicians as well controlled rose from 59% to 74%. Asthma care can be improved by supporting practice change through statewide QI learning collaboratives.


Suicide attempts among adolescents in northeastern Slovenia: a 25 year report.
Slovenia is one of the countries with the highest national suicide rates (30/100,000/year). The rate of suicide attempts is accordingly high, for both adolescents and adults. Suicidal children and adolescents from the four North-eastern regions of Slovenia are hospitalised at the Child and Adolescent Psychiatry Unit of the General Hospital Maribor. The aim of this study was to show the pattern of changes in these hospitalisations along 25 years. The data was collected retrospectively, using chart review of this unit by a psychiatrist for the years 1978 through 2004. The data consists of two different samples. The first sample contains gender distribution (n = 774) from 1978 to mid 2004 with 664 girls and 110 boys, and the second sample (n = 1,477) consisted of suicide attempts as well as alcohol (n = 772) and drug abuse (n = 115) data for the last decade. The number of hospitalisations was increasing in a wavy curve with average 7,5 times more admitted girls than boys. In 98%, the suicide method was intoxication, and most were additionally diagnosed with "adolescent crisis" (ICD-10: F93.8). The rise in the number of admitted suicidal adolescents was partly consequent to the improvement of their detection maybe because 25 years ago most of these cases were recorded as "accidental poisonings" and did not include the diagnosis of a suicide attempt. The socio-economic changes characteristic of a country in transition also contributed to this increase, as did the development of the Unit with more trained staff and advanced treatment.


Goal-setting And Achievement In Activity Tracking Apps: A Case Study Of MyFitnessPal.
Activity tracking apps often make use of goals as one of their core motivational tools. There are two critical components to this tool: setting a goal, and subsequently achieving that goal. Despite its crucial role in how a number of prominent self-tracking apps function, there has been relatively little investigation of the goal-setting and achievement aspects of self-tracking apps. Here we explore this issue, investigating a particular goal setting and achievement process that is extensive, recorded, and crucial for both the app and its users' success: weight loss goals in MyFitnessPal. We present a large-scale study of 1.4 million users and weight loss goals, allowing for an unprecedented detailed view of how people set and achieve their goals. We find that, even for difficult long-term goals, behavior within the first 7 days predicts those who ultimately achieve their goals, that is, those who lose at least as much weight as they set out to, and those who do not. For instance, high amounts of early weight loss, which some researchers have classified as unsustainable, leads to higher goal achievement rates. We also show that early food intake, self-monitoring motivation, and attitude towards the goal are important factors. We then show that we can use our findings to predict goal achievement with an accuracy of 79% ROC AUC just 7 days after a goal is set. Finally, we discuss how our findings could inform steps to improve goal achievement in self-tracking apps.


Sore throat · vaginal discharge · labial ulcer · Dx?
The patient complained of worsening vaginal pain and increased vaginal discharge, but reported resolution of her back and chest pain. She also said that a week earlier, she'd had a fever that reached 104° F and a sore throat. She denied urinary frequency/urgency, sexual activity, or sexual abuse.


Cyclosporine A for the treatment of refractory nephrotic syndrome with renal dysfunction.
Cyclosporine A (CsA) is an immunosuppressant agent and is utilized as a second-line drug therapy for refractory nephrotic syndrome (RNS). In general, the use of CsA is strictly controlled in patients with an estimated glomerular filtration rate (eGFR) <30-40 ml/min/1.73 m2, and little is known about the safety and efficacy of CsA treatment in patients with RNS complicated by renal dysfunction. In the present study, the clinical data of 10 patients with RNS and renal dysfunction, who received CsA treatment between 2000 and 2009 in the Kidney Institute of PLA, were reviewed retrospectively. Pathologically, these patients included six cases with minimal change, two cases of diffuse mesangial proliferation and two cases of focal segmental glomerulosclerosis. Six months subsequent to the initiation of the CsA treatment, six patients achieved complete remission, two patients achieved remarkable remission and two patients achieved partial remission. Renal function was improved in all patients as represented by the improvement in the eGFR (28.6±3.8 ml/min/1.73 m2 prior to treatment versus 99.3±21.9 ml/min/1.73 m2 6 months subsequent to treatment). Few adverse CsA-related events were observed. These results suggest that renal dysfunction is not an absolute contraindication for CsA treatment in patients with RNS. The use of CsA is safe and efficacious and may, in certain cases, improve renal function in patients with RNS and renal impairment.


Green Synthesis and Characterization of Carboxymethyl Cellulose Fabricated Silver-Based Nanocomposite for Various Therapeutic Applications.
The current study proposed the simple, eco-friendly and cost-effective synthesis of carboxymethyl cellulose (CMC) structured silver-based nanocomposite (CMC-AgNPs) using Syzygium aromaticum buds extract. The CMC-AgNPs were characterized by ultraviolet (UV) spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transmission infra-red (FTIR), energy-dispersive X-ray (EDX), and dynamic light scattering (DLS) techniques. The synthesized nanocomposites were evaluated for their bactericidal kinetics, in-vivo anti-inflammatory, anti-leishmaniasis, antioxidant and cytotoxic activities using different in-vitro and in-vivo models. The spherical shape nanocomposite of CMC-AgNPs was synthesized with the mean size range of 20-30 nm, and the average pore diameter is 18.2 nm while the mean zeta potential of -31.6 ± 3.64 mV. The highly significant (P < 0.005) antibacterial activity was found against six bacterial strains with the ZIs of 24.6 to 27.9 mm. More drop counts were observed in Gram-negative strains after 10 min exposure with CMC-AgNPs. Significant damage in bacterial cell membrane was also observed in atomic force microscopy (AFM) after treated with CMC-AgNPs. Nanocomposite showed highly significant anti-inflammatory activity in cotton pellet induced granuloma model (Phase I) in rats with the mean inhibitions of 43.13% and 48.68% at the doses of 0.025 and 0.05 mg/kg, respectively, when compared to control. Reduction in rat paw edema (Phase II) was also highly significant (0.025 mg/kg; 42.39%; 0.05 mg/kg, 47.82%). At dose of 0.05 mg/kg, CMC-AgNPs caused highly significant decrease in leukocyte counts (922 ± 83), levels of CRP (8.4 ± 0.73 mg/mL), IL-1 (177.4 ± 21.3 pg/mL), IL-2 (83.7 ± 11.5 pg/mL), IL-6 (83.7 ± 11.5 pg/mL) and TNF-α (18.3 ± 5.3 pg/mL) as compared to control group. CMC-AgNPs produced highly effective anti-leishmaniasis activity with the viable Leishmania major counts decreased up to 36.7% within 24 h, and the IC50 was found to be 28.41 μg/mL. The potent DPPH radical scavenging potential was also observed for CMC-AgNPs with the IC50 value of 112 μg/mL. Furthermore, the cytotoxicity was assessed using HeLa cell lines with the LC50 of 108.2 μg/mL. The current findings demonstrate positive attributes of CMC fabricated AgNPs as a promising antibacterial, anti-inflammatory, anti-leishmaniasis, and antioxidant agent with low cytotoxic potential.


Impact of statin use before the onset of acute myocardial infarction on coronary plaque morphology of the culprit lesion.
Statins favorably stabilize coronary plaque. We evaluated the impact of statin use before the onset of acute myocardial infarction (AMI) on culprit lesion plaque morphology. Patients (n = 127) with AMI were divided into either a statin group (n = 31) or a nonstatin group (n = 96) based on statin use before the onset of AMI. Coronary plaque morphology of the culprit lesion was evaluated using intravascular ultrasound virtual histology (IVUS-VH) with radiofrequency data analysis before coronary intervention. The IVUS-VH identified 4 types of plaque components: fibrous, fibrofatty, dense calcium, and necrotic core. The IVUS-VH showed less percentage of necrotic area, greater percentage fibrous area, and greater percentage of fibrofatty area of the culprit lesion in the statin group. In conclusion, statin use before the onset of AMI might have effects on coronary plaque morphology of the AMI culprit lesion with less necrotic core and greater fibrous and fibrofatty component.


Fibrinogen degradation products in urological malignant tumors.
Fibrinogen degradation products (FDP) were determined in a series of 98 patients with malignant urological tumors using a staphylococcal clumping test. The results are compared with the FDP of 61 urological patients without malignant tumors. No difference between the series of radically operated tumor patients and the control group could be found. The FDP in a series of patients with persistent tumors were clearly higher than those of the control group: especially the results for patients with renal cell carcinoma were significantly higher. The highest concentration of FDP was found in patients with metastases. Therefore, FDP in serum could be a possible tumor marker for patients with renal cell carcinoma.


Therapeutic effects of isoflavones on impaired salivary secretion.
Dry mouth, which is characterized by decreased salivation, has a number of causes; the involvement of estrogen has been suggested as symptoms typically develop in middle-aged females. However, there is a lack of consensus regarding the treatment of this condition. Soy isoflavones, a subgroup of flavonoids, are abundantly found in the soy germ. They are thought to exert a number of effects by specifically binding to estrogen receptors due to their structural similarity to estrogen. Recently, soy isoflavones have been found to exert antioxidant effects, ameliorating disorders caused by reactive oxygen/free radicals. Based on these observations, the effects of soybean isoflavones on impaired salivary secretion were studied in patients with dry mouth. Soy isoflavone aglycones were administered at 25 mg per day to 15 subjects with an average age of 67.9 ± 8.0 years for 2 months, and salivary secretion was analyzed. The results showed a significant improvement based on the saliva flow rate and self-completed questionnaire, thus suggesting the usefulness of isoflavones in improving the symptoms of salivary gland hypofunction.


Catalytic asymmetric Mannich-type reactions of α-cyano α-sulfonyl carbanions.
An efficient asymmetric Mannich-type reaction of α-cyano α-sulfonyl carbanions has been achieved by exploiting the structural modularity and anion-recognition ability of chiral 1,2,3-triazolium ions. This protocol has proven to be applicable to a variety of N-Boc imines and cyanosulfones, affording β-amino α-cyanosulfones in excellent yields with high stereoselectivities.


Can valerian improve the sleep of insomniacs after benzodiazepine withdrawal?
The authors studied the sleep of patients with insomnia who complained of poor sleep despite chronic use of benzodiazepines (BZDs). The sample consisted of 19 patients (mean age 43.3+/-10.6 years) with primary insomnia (DSM-IV), who had taken BZDs nightly, for 7.1+/-5.4 years. The control group was composed of 18 healthy individuals (mean age 37+/-8 years). Sleep electroencephalogram (EEG) of the patients was analyzed with period amplitude analysis (PAA) and associated algorithms, during chronic BZD use (Night 1), and after 15 days of a valerian placebo trial (initiated after washout of BZD, Night 2). Sleep of control subjects was monitored in parallel. Valerian subjects reported significantly better subjective sleep quality than placebo ones, after BZD withdrawal, despite the presence of a few side effects. However, some of the differences found in sleep structure between Night 1 and Night 2 in both the valerian and placebo groups may be due to the sleep recovery process after BZD washout. Example of this are: the decrease in Sleep Stage 2 and in sigma count; the increase in slow-wave sleep (SWS), and delta count, which were found to be altered by BZD ingestion. There was a significant decrease in wake time after sleep onset (WASO) in valerian subjects when compared to placebo subjects; results were similar to normal controls. Nonetheless, valerian-treated patients also presented longer sleep latency and increased alpha count in SWS than control subjects. The decrease in WASO associated with the mild anxiolytic effect of valerian appeared to be the major contributor to subjective sleep quality improvement found after 2-week of treatment in insomniacs who had withdrawn from BDZs. Despite subjective improvement, sleep data showed that valerian did not produce faster sleep onset; the increase in alpha count compared with normal controls may point to residual hyperarousabilty, which is known to play a role in insomnia. Nonetheless, we lack data on the extent to which a sedative drug can improve alpha sleep EEG. Thus, the authors suggest that valerian had a positive effect on withdrawal from BDZ use.


[Interstitial Pneumonia and Emphysema].
Interstitial pneumonia (IP) and chronic obstructive pulmonary disease (COPD) are representative diseases of restrictive pulmonary dysfunction and obstructive pulmonary dysfunction, respectively. In the preoperative anesthesia clinic, anesthesiologists are frequently asked to assess the anesthesia management of patients with these diseases. In respiratory function tests, IP is detected as a decrease in % vital capacity (< 80%), and COPD as a decrease in % FEV1.0 (< 70%). Other key factors which affect the assessment are; 1) severity assessment that affects the safety of anesthesia management, 2) prognostic evaluation including the acute exacerbation in the postoperative period, and 3) patient-related factors (age, life degree of autonomy, other comorbidities, surgery-related factors, and anesthesia method). In the patients in the disease stage I or II, anesthesia management is relatively safe. On the other hand, the patients in the disease stage IV have no surgical indication except life-saving emergent situation. In another words, anesthesiologists are required to make the judgment for the anesthesia management of the patient in the disease stage III, based on the assessment of patient-related factors, surgery-related factors, and prognosis.


Assessment of the construct validity of the Australian Health Star Rating: a nutrient profiling diagnostic accuracy study.
Nutrient profiling models classify the healthiness of foods based on their nutritional composition and provide the science that underlies nutrition signposting schemes. The two objectives were to examine the construct validity of the Health Star Rating (HSR) system by determining its diagnostic accuracy and to detect the optimal HSR cutoff points to define healthiness in packaged dairy foods. We hypothesised that ultra-processed dairy, defined by NOVA, would have less stars (less healthy) and non-ultra-processed dairy would have more stars (more healthy). The diagnostic accuracy of the HSR system used for 621 dairy foods for sale in an Australian regional supermarket was investigated. The healthiness of packaged dairy was measured using the NOVA food classification system. The dairy beverages model was found to discriminate between healthy and less healthy dairy beverages as classified by NOVA (AUC: 0.653; 95% CI: 0.556-0.750; P=0.005). A receiver operating characteristic curve analysis for dairy beverages demonstrated that the optimal cutoff point corresponded to a rating of four stars. There was no discrimination power when using the HSR for predicting the health value of yoghurt and other dairy, or cheeses. At the optimal cutoff point of four stars the HSR has a high sensitivity but a low specificity to correctly classify healthy packaged dairy beverages, as defined by NOVA. We provide evidence to support the construct validity of the HSR model for dairy beverages, but not for the models used for yoghurts and other dairy products, or cheeses.


Fabrication for multilayered composite thin films by dual-channel vacuum arc deposition.
A flexible dual-channel curvilinear electromagnetic filter has been designed and constructed to fabricate multilayered composite films in vacuum arc ion plating. The filter possesses two guiding channels and one mixing unit. Multilayered TiN/AlN and TiAlN composite films can be produced by controlling the frequency or interval of the two cathodes. The x-ray photoelectron spectroscopy and low-angle x-ray diffraction results reveal the periodic Ti and Al structures in the TiN/AlN films. The TiAlN films exhibit a smooth surface morphology confirming effective filtering of macroparticles by the filter. High temperature oxidation conducted at 700 degrees C for an hour indicates that the weight increment in the TiAlN films produced by the dual filter is only half of that of the TiAlN films produced without a filter, thereby showing better resistance against surface oxidation.


[Research progress of cell sheet technology in oral tissue engineering].
Cell sheet technology (CST) demonstrates the innovation and advantage by overcoming some immanent shortcomings of traditional tissue engineering. To review the research progress of CST in oral tissue engineering. The related home and abroad literature about CST and its application in stomatology was extensively reviewed and analyzed. Compared to the traditional tissue engineering technology, CST has the features of high seeding density, abundant matrix, good biological compatibility, and perfect operability, which can improve the survival rate of cell transplantation and promote functional reconstruction. It is reported that CST has been successfully used in the following fields, repair and reconstruction of periodontium, soft tissues of oral mucosa, and bones in maxillofacial region. With the development of CST and combined with the traditional tissue engineering technologies, it will promote the tissue engineering further progress in stomatology.


Predictors of Long-Term School-Based Behavioral Outcomes in the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder.
To explore predictors of 8-year school-based behavioral outcomes in attention-deficit/hyperactivity disorder (ADHD). We examined potential baseline predictors of school-based behavioral outcomes in children who completed the 8-year follow-up in the multimodal treatment study of children with ADHD. Stepwise logistic regression and receiver operating characteristic (ROC) analysis identified baseline predictors that were associated with a higher risk of truancy, school discipline, and in-school fights. Stepwise regression analysis explained between 8.1% (in-school fights) and 12.0% (school discipline) of the total variance in school-based behavioral outcomes. Logistic regression identified several baseline characteristics that were associated with school-based behavioral difficulties 8 years later, including being male (associated with truancy and school discipline), African American (school discipline, in-school fights), increased conduct disorder (CD) symptoms (truancy), decreased affection from parents (school discipline), ADHD severity (in-school fights), and study site (truancy and school discipline). ROC analyses identified the most discriminative predictors of truancy, school discipline, and in-school fights, which were Aggression and Conduct Problem Scale Total score, family income, and race, respectively. A modest, but nontrivial portion of school-based behavioral outcomes, was predicted by baseline childhood characteristics. Exploratory analyses identified modifiable (lack of paternal involvement, lower parental knowledge of behavioral principles, and parental use of physical punishment), somewhat modifiable (income and having comorbid CD), and nonmodifiable (African American and male) factors that were associated with school-based behavioral difficulties. Future research should confirm that the associations between earlier specific parenting behaviors and poor subsequent school-based behavioral outcomes are, indeed, causally related and independent cooccurring childhood psychopathology. Future research might target increasing paternal involvement and parental knowledge of behavioral principles and reducing use of physical punishment to improve school-based behavioral outcomes in children with ADHD.


Clinical and subclinical leaks after low colorectal anastomosis: a clinical and radiologic study.
This study was designed to examine the natural history of subclinical leaks and their effect on bowel function and quality of life and to evaluate water-soluble contrast enema features that predict anastomotic healing after leaks. Consecutive patients who underwent low rectal anastomosis were followed up postoperatively for leaks. All leaks were confirmed radiologically with CT scanning and water-soluble contrast enema imaging. Water-soluble contrast enemas were serially repeated to identify healing. Characteristics on initial water-soluble contrast enema were correlated with observed healing. Postoperatively, patients were required to fill in a quality of life and a bowel function questionnaire. A total of 138 patients underwent low rectal anastomosis procedures with a median follow-up period of 26 (interquartile range, 19-37) months. There were 23 documented leaks of which 13 (9 percent) presented clinically and 10 (8 percent) presented subclinically. Ileostomy closure was possible in 4 of 13 (30 percent) patients with a clinical leak and all 10 (100 percent) patients with a subclinical leak. Median quality of life scores were lower for patients with clinical leaks and no ileostomy closure (P = 0.03). Bowel function for subclinical leak patients and clinical leak patients with ileostomy closure were similarly impaired. The presence of a cavity (P = 0.01) and a stricture (P = 0.01) at the anastomotic site were unfavorable radiologic features associated with nonhealing. Subclinical leaks are more benign in their natural history compared with clinical leaks. Quality of life and bowel function is no better in patients with a subclinical leak compared with patients with a clinical leak who have ileostomy closure. Anastomotic leaks may resolve if favorable radiologic features are present.


Using qualitative methods in developing an instrument to identify barriers to self-care among persons with type 2 diabetes mellitus.
To develop a questionnaire to address barriers and self-care behaviour among persons with type 2 diabetes mellitus. Several instruments are available in the literature to measure barriers to self-care in this population, but many of them present limitations in its psychometric validation process, and lack of theoretical background. Content validation study using multiple qualitative methods. A systematic review was conducted, and two focus groups with fifteen participants (n = 15) were analysed to identify key topics and categories concerning barriers and self-care behaviour. These categories were used to generate items that were subjected to expert scrutiny, using the Delphi technique. The resulting list of items was tested for readability and comprehension by nine diabetic patients (n = 9), through cognitive interviews. The whole process was conducted in accordance with the Theory of Planned Behaviour. The mean age (standard deviation) of participants in the focus groups and cognitive interviews was 66·05 (8·47) and 63·11 (6·13) years, respectively. 46·7% of the members of the focus groups and 44·4% of those interviewed were female, and the mean duration (standard deviation) of their diabetes was 6·53 (3·17) and 4·89 (3·84) years, respectively. After the qualitative analysis, 27 codes were obtained. Thereafter, items were generated in accordance with the dimensions of this theory: attitudes towards the behaviour (n = 23), social norms (n = 13), perceived behavioural control (n = 17) and behavioural intention (n = 15). A rigorous process of content validation with multiple methods was implemented to obtain an instrument aimed at addressing barriers and self-care behaviour of patients with type 2 Diabetes Mellitus. An instrument theoretically rooted and supported on professional and patients' views is available to assess self-care behaviours in patients with type 2 Diabetes Mellitus. The evaluation of its reliability and construct validity will determine the instrument's value and practical application in the clinical context.


Immunological detection of specific proteins in total cell extracts by fractionation in gels and transfer to diazophenylthioether paper.
We describe a sensitive immunological procedure for the detection of specific proteins in total cell extracts and for the comparison of antigenically related polypeptides. Proteins are fractionated in polyacrylamide gels and transferred electrophoretically to diazophenylthioether paper, to which they bind covalently. Specific proteins are identified by incubation with specific antibody and 125 I-labeled protein A from Staphylococcus aureus, followed by autoradiography. High-resolution separation of proteins prior to transfer is achieved by polyacrylamide gradient gel electrophoresis in the presence of sodium dodecyl sulfate or by nonequilibrium pH gradient electrophoresis, followed by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Further information can be obtained by limited enzymatic proteolysis of the proteins in the gel following polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and analysis of the cleavage products by gel electrophoresis at right angles to the first gel. We show the application of this technique to the detection and comparison in extracts from infected cells of proteins related immunologically to the simian virus 40 capsid proteins VP1 and VP3.


[Effect of pharmaceutical care in the diagnosis of Helicobacter pylori infection using 13C-urea breath test].
The urea breath test (UBT) is used widely for assessment of Helicobacter pylori (H. pylori) eradication after treatment. A false-negative UBT is common during administration of anti-ulcer drugs and immediately after their discontinuation. It was thought that the pharmaceutical care by the pharmacists was necessary for the diagnostic accuracy of UBT after H. pylori eradication therapy. Therefore, we investigated the effect of pharmaceutical care on diagnosis based on assessment of UBT. The patients who performed UBT were classified into two groups according to the pharmacists' intervention. From 2008 April to 2009 September, the number of the patients taken pharmaceutical care was 57 (intervention group) and that of the patients taken no pharmaceutical care was 62 (control group). When drugs for H. pylori infection and anamnestic therapy were same, the percentage that avoided administration of double drugs was significantly increased by the pharmaceutical care (93.3% in intervention group versus 21.4% in control group, p<0.05). Therefore, the percentage of noncompliance that performed UBT 4 weeks after treatment onward was significantly decreased by the pharmaceutical care (1.6% in intervention group versus 17.5% in control group, p<0.05). Moreover, the percentage of recurrence after treatment was significantly decreased, there were 3.3% in the intervention group and 14.0% in the control group. In conclusion, it was very important that the pharmacists take care in the management of treatment and UBT for H. pylori eradication therapy.


5-HT Receptor Nomenclature: Naming Names, Does It Matter? A Tribute to Maurice Rapport.
The naming of 5-HT receptors has been challenging, especially in the early days when the concept of multiple receptors for a single neurotransmitter was considered to be unrealistic at best. Yet pharmacological (rank orders of potency in functional or biochemical settings) and transductional evidence (second messengers, electrophysiology) clearly indicated the existence of receptor families and subfamilies. The genetic revolution, with the cloning and study of recombinantly expressed receptors, and eventually the cloning of the human and other genomes have made such reservations obsolete. Further, the advances in structural biology, with the possibility to study ligand receptor complexes as crystals and/or using solution NMR have largely confirmed the complexity of the 5-HT receptor system: species differences, existence of multiple receptor active and inactive states, splice variants, editing variants, complexes with multiple interacting proteins and transduction bias. This is a short personal history on how advances in biochemistry, molecular biology, biophysics, imaging and medicinal chemistry, some lateral thinking, and a decent amount of collaborative spirit within the 5-HT receptor nomenclature committee and the 5-HT community at large have helped to better define the pharmacology of the 5-HT receptor family.


"A vengefulness of the impotent": the pain of in-group inferiority and schadenfreude toward successful out-groups.
Nietzsche (1887/1967) suggested that the emotional pain individuals feel about their in-group's inferiority leads them to feel the pleasure of schadenfreude when a successful out-group fails. To test this idea, 2 studies examined a fictitious competition between real universities. Individuals' pain about their in-group's inferiority explained schadenfreude at the failure of a successful out-group better than dislike of the out-group, interest in the domain of competition, illegitimacy of the out-group's success, and illegitimacy of the in-group's inferiority. In addition, emotions regarding the out-group's success (i.e., envy, dislike-based anger, and illegitimacy-based anger) were weaker explanations of schadenfreude than the pain of in-group inferiority and anger based in this pain (which Nietzsche referred to as ressentiment). Thus, schadenfreude has more to do with the inferiority of the self than with the success of others. As well as providing evidence for a specific form of prejudice grounded in group-based emotions, this research also revives displacement explanations of prejudice toward 3rd parties.


Computer aided epitope design as a peptide vaccine component against Lassa virus.
Lassa virus (LASV) is an arena virus causing hemorrhagic fever and it is endemic in several regions of West Africa. The disease-causing virus records high mortality rate in endemic regions due to lack of appropriate treatment and prevention strategies. Therefore, it is of interest to design and develop viable vaccine components against the virus. We used the Lassa virus envelope glyco-proteins as a vaccine target to identify linear peptides as potential epitopes with immunogenic properties by computer aided epitope prediction tools. We report a T-cell epitope 'LLGTFTWTL' and a B-cell epitope 'AELKCFGNTAVAKCNE' with predicted potential immunogenicity for further in vivo and in vitro consideration.


Use of Tenecteplase in Acute Ischemic Stroke in the Time of SARS-CoV-2.
Tenecteplase (TNK) is a fibrinolytic drug that is administrated in a single bolus, recommended in eligible patients with acute ischemic stroke prior to mechanical thrombectomy. This study explores its usefulness in adverse situations, such as the SARS-CoV-2 pandemic. We conducted a retrospective study involving consecutive patients with suspected acute ischemic stroke treated either with intravenous fibrinolysis with alteplase during 2019 or with TNK (.25 mg/kg) between March 2020 and February 2021. A comparative analysis was made to compare patient treatment times and prognosis. A total of 117 patients treated with alteplase and 92 with TNK were included. No significant differences were observed in age, main vascular risk factors or previous treatments. The median National Institutes of Health Stroke Scale was 8 in the alteplase group and 10 in those treated with TNK (P = .13). Combined treatment with mechanical thrombectomy was performed in 47% in the alteplase group and 46.7% in the TNK group; Thrombolysis In Cerebral Infarction scale 2b-3 recanalization was achieved in 83% and 90.7%, respectively (P = .30). There was a decrease in onset-to-needle median time (165 min vs 140 min, P < .01) and no significant variations in door-needle median time. There was no significant difference in the incidence of symptomatic hemorrhagic transformation in mortality or functional independence at 3 months. The easier administration of TNK has improved the accessibility of fibrinolytic therapy, even in adverse circumstances, such as the COVID-19 pandemic. Its use appears to be safe and effective, even in patients who are not candidates for mechanical thrombectomy.


Validation of Lithuanian Arthroplasty Register Telephone Survey of 2769 Patients Operated for Total Knee Replacement.
Background and objectives: The aim of our study is to validate the registration of knee arthroplasty revisions in the Lithuanian Arthroplasty Register (LAR) and thus give an indication of the accuracy of the published revision rates. Materials and methods: A total of 4269 primary total knee arthroplasties (TKAs) registered in the LAR between 2013 and 2015 were included. Two years after surgery the patients were contacted by phone in order to inquire if they had been subject to revision. The information from the patients was then cross checked against what had been registered in the LAR, and in case of a revision not having been registered hospital charts were investigated. Thus, the patients were followed up with regarding revision and/or death until 2017. A true revision was defined as an addition, exchange, or removal of one or all components. Results: Out of 4269 primary TKAs, we managed to contact and interview 2769 patients. Nine small hospitals were not able to provide contact details (telephone numbers) for 533 patients (549 knees). Sixty-seven patients (67 knees) were deceased (data from the Lithuanian National Census Register) and a further 438 patients (565 knees) appeared to have a wrong or non-valid telephone number, leaving 3031 (3091 knees) patients being contacted. Of those, 262 patients (266 knees) refused to participate in the study which left 2769 responders (2825 knees). Sixty-one patients said that reoperation had been performed on the index knee within two years of their primary surgery. After checking with the clinics, 10 were surgical procedures on the knee but not true revisions by our criteria. Out of the 51 true revisions we found that 46 were registered to the LAR as revised, while five (9.8%) revisions were missing. Conclusions: We conclude that the Lithuanian Arthroplasty Register has a good completeness of registered revision TKAs as only 9.8% of revisions were missing.


Orbital pacing of carbon fluxes by a ∼9-My eccentricity cycle during the Mesozoic.
Eccentricity, obliquity, and precession are cyclic parameters of the Earth's orbit whose climatic implications have been widely demonstrated on recent and short time intervals. Amplitude modulations of these parameters on million-year time scales induce "grand orbital cycles," but the behavior and the paleoenvironmental consequences of these cycles remain debated for the Mesozoic owing to the chaotic diffusion of the solar system in the past. Here, we test for these cycles from the Jurassic to the Early Cretaceous by analyzing new stable isotope datasets reflecting fluctuations in the carbon cycle and seawater temperatures. Our results document a prominent cyclicity of ∼9 My in the carbon cycle paced by changes in the seasonal dynamics of hydrological processes and long-term sea level fluctuations. These paleoenvironmental changes are linked to a great eccentricity cycle consistent with astronomical solutions. The orbital forcing signal was mainly amplified by cumulative sequestration of organic matter in the boreal wetlands under greenhouse conditions. Finally, we show that the ∼9-My cycle faded during the Pliensbachian, which could either reflect major paleoenvironmental disturbances or a chaotic transition affecting this cycle.


Negative pressure therapy in the orofacial region in oncological patients - two case reports.
Chronic wounds and their problematic healing is a widely discussed topic in all branches of medicine. In recent years, vacuum therapy appears to be a very successful non-invasive method supporting the healing of these wounds. The aim of this paper is to demonstrate the possibility of utilizing a vacuum system in the orofacial area where other conservative and surgical procedures have failed. The case reports demonstrate the use of vacuum therapy in non-healing postoperative wounds in cancer patients. Vacuum therapy has limited use in the orofacial area, but based on our experience, we can conclude that it has a very positive effect on the healing of chronic wounds. Thanks to this treatment, it was possible to reduce the frequency of dressings and significantly shorten the length of hospital stay. Despite these advantages, however, it is necessary to adhere to the conditions for the application of vacuum treatment.


Emerging role of autophagy in kidney function, diseases and aging.
Autophagy is a highly conserved process that degrades cellular long-lived proteins and organelles. Accumulating evidence indicates that autophagy plays a critical role in kidney maintenance, diseases and aging. Ischemic, toxic, immunological, and oxidative insults can cause an induction of autophagy in renal epithelial cells modifying the course of various kidney diseases. This review summarizes recent insights on the role of autophagy in kidney physiology and diseases alluding to possible novel intervention strategies for treating specific kidney disorders by modifying autophagy.


Responsivity to offspring's expression of emotion among childhood-onset depressed mothers.
This study examined responsivity of mothers with childhood-onset depression (COD) in relation to children's overt expression of positive and negative emotion. It was hypothesized that COD and control mothers would differ in contingent responsivity to their children's expression of both positivity and different types of negative emotionality. Using observations and maternal reports of their own emotional reactions, COD mothers were found to be less responsive to children's expression of distress. A Gender x Group interaction was also found with respect to observed maternal responsiveness to child positivity, such that COD mothers were more responsive to girls' than boys' expression of positivity. The results are discussed in reference to transactional models of early child psychopathology.


Needles, Jabs and Jags: a qualitative exploration of barriers and facilitators to child and adult immunisation uptake among Gypsies, Travellers and Roma.
Gypsies, Travellers and Roma (referred to as Travellers) are less likely to access health services including immunisation. To improve immunisation rates, it is necessary to understand what helps and hinders individuals in these communities in taking up immunisations. This study had two aims. 1. Investigate the views of Travellers in the UK on the barriers and facilitators to acceptability and uptake of immunisations and explore their ideas for improving immunisation uptake; 2. Examine whether and how these responses vary across and within communities, and for different vaccines (childhood and adult). This was a qualitative, cross-sectional interview study informed by the Social Ecological Model. Semi-structured interviews were conducted with 174 Travellers from six communities: Romanian Roma, English Gypsy/Irish Travellers (Bristol), English Gypsy (York), Romanian/Slovakian Roma, Scottish Show people (Glasgow) and Irish Traveller (London). The focus was childhood and selected adult vaccines. Data were analysed using the Framework approach. Common accounts of barriers and facilitators were identified across all six Traveller communities, similar to those documented for the general population. All Roma communities experienced additional barriers of language and being in a new country. Men and women described similar barriers and facilitators although women spoke more of discrimination and low literacy. There was broad acceptance of childhood and adult immunisation across and within communities, with current parents perceived as more positive than their elders. A minority of English-speaking Travellers worried about multiple/combined childhood vaccines, adult flu and whooping cough and described barriers to booking and attending immunisation. Cultural concerns about antenatal vaccines and HPV vaccination were most evident in the Bristol English Gypsy/Irish Traveller community. Language, literacy, discrimination, poor school attendance, poverty and housing were identified as barriers across different communities. Trustful relationships with health professionals were important and continuity of care valued. The experience of many Travellers in this study, and the context through which they make health decisions, is changing. This large study identified key issues that should be considered when taking action to improve uptake of immunisations in Traveller families and reduce the persistent inequalities in coverage. Current Controlled Trials ISRCTN20019630 .


Temporal coherence versus harmonicity in auditory stream formation.
This study sought to investigate the influence of temporal incoherence and inharmonicity on concurrent stream segregation, using performance-based measures. Subjects discriminated frequency shifts in a temporally regular sequence of target pure tones, embedded in a constant or randomly varying multi-tone background. Depending on the condition tested, the target tones were either temporally coherent or incoherent with, and either harmonically or inharmonically related to, the background tones. The results provide further evidence that temporal incoherence facilitates stream segregation and they suggest that deviations from harmonicity can cause similar facilitation effects, even when the targets and the maskers are temporally coherent.


Serum antiphospholipid antibody status may not be associated with the pregnancy outcomes of patients undergoing in vitro fertilization.
Antiphospholipid syndrome (APS) is an autoimmune disease that is associated with recurrent pregnancy loss. It is still controversial whether the presence of antiphospholipid antibodies (aPL) in the serum of patients with in vitro fertilization-embryo transfer (IVF-ET) has a negative effect on the outcomes. In view of the discrepancies, a meta-analysis of the published data was performed to explore the relationship of aPL and IVF-ET outcomes. We searched for all published articles indexed in PubMed, Web of Science, and Cochrane Library, which were retrieved up to April, 2021. A total of 921 studies were yielded, of which 6 finally met the inclusion criteria. We carried out the meta-analysis by pooling results of these studies with Review Manager 5.3 software. The effect index was measured with 95% confidence intervals (CIs) of the relative risks (RRs). Six eligible studies were included in this meta-analysis, involving 3214 patients. Our results showed that positive aPL was not associated with decreased clinical pregnancy rate (RR 0.97; 95% CI 0.91-1.04). There was no correlation between positive aPL and increased miscarriage risk (RR 1.22; 95% CI 0.94-1.58). Only 5 of the 6 studies referred to live birth rate, but still no association was found between them (RR 0.95; 95% CI 0.81-1.11). The results showed that the presence of positive aPL neither decreased clinical pregnancy rate and live birth rate, nor increased miscarriage rate in women undergoing IVF, which is differed from the opinion of clinical practice. More prospective studies with high quality and larger sample size are needed to evaluate the relationship between positive aPL and outcomes of IVF-ET.


Parental experiences of eczema advice in online parenting forums: a qualitative interview study.
Parents of children with eczema are increasingly turning to online parenting forums for advice about how to manage it. Little is known about how parents make sense of advice about eczema treatments in online forums, and how it affects their management of childhood eczema. To explore how parents of children with eczema make sense of and act on advice about eczema treatments exchanged in online parenting forums. Qualitative interviews with parents of children with eczema from the UK. Fifteen parents were recruited through online advertisements and snowball sampling. Semi-structured interviews were carried out face to face or by telephone, and analysed inductively using reflexive thematic analysis. When seeking advice from online parenting forums about eczema treatments, parents described appraising the credibility of advice and considering the potential suitability of treatments that were recommended in the forum. Parents proceeded to make sense of online advice through either reading advice and not engaging in online discussions, or actively engaging in online discussions to direct topics and seek most relevant advice. Parents discussed advice received online in subsequent consultations with their GP and requested prescriptions of recommended treatments. Some parents described trying new treatments without consulting their GP. Understanding how parents appraise, make sense of, and act on online advice could support healthcare professionals to disseminate advice appropriately, ask additional questions, and signpost parents to reliable online resources.


Incidence of acute low-back injury among older workers in a cohort of material handlers.
Injuries to the low back are the most common cause for injury claims among material handlers. Previous studies have shown conflicting results about how age affects risk of low-back injury. This study describes the incidence of acute low-back injury by age, gender, length of employment, and lifting intensity measured by job classification in a cohort of material handlers. The cohort included all material handlers employed at a large home improvement retail chain in California from 1989 through 1994. The cohort accrued approximately 50,000 full time equivalents over the study period. A total of 2152 low-back injuries were reported during the study period. Compared to workers aged younger than 45, the crude rate ratio for workers aged 45 to 54 was 0.78, and for workers aged 55 and above was 0.84. However, this age difference was not apparent among length of employment strata or among jobs with low or medium lifting intensity. A higher proportion of workers over the age of 55 missed work time because of their injury, and workers over 45 had a higher average number of lost workdays per injury. This research indicates that workers over age 55 had similar injury rates to workers younger than age 55, even when considering lifting intensity and length of employment. However, their injuries may cause a longer period of disability.


Gait parameter adjustments for walking on a treadmill at preferred, slower, and faster speeds in older adults with down syndrome.
The combined effects of ligamentous laxity, hypotonia, and decrements associated with aging lead to stability-enhancing foot placement adaptations during routine overground walking at a younger age in adults with Down syndrome (DS) compared to their peers with typical development (TD). Our purpose here was to examine real-time adaptations in older adults with DS by testing their responses to walking on a treadmill at their preferred speed and at speeds slower and faster than preferred. We found that older adults with DS were able to adapt their gait to slower and faster than preferred treadmill speeds; however, they maintained their stability-enhancing foot placements at all speeds compared to their peers with TD. All adults adapted their gait patterns similarly in response to faster and slower than preferred treadmill-walking speeds. They increased stride frequency and stride length, maintained step width, and decreased percent stance as treadmill speed increased. Older adults with DS, however, adjusted their stride frequencies significantly less than their peers with TD. Our results show that older adults with DS have the capacity to adapt their gait parameters in response to different walking speeds while also supporting the need for intervention to increase gait stability.


Dual role of the nuclear factor of activated T cells insert region in DNA recognition and cooperative contacts to activator protein 1.
The transcription factors nuclear factor of activated T cells (NFAT) and activator protein 1 (AP-1) coordinately regulate cytokine gene expression in activated T-cells by binding to closely juxtaposed sites in cytokine promoters. The structural basis for cooperative binding of NFAT and AP-1 to these sites, and indeed for the cooperative binding of transcription factors to composite regulatory elements in general, is not well understood. Mutagenesis studies have identified a segment of AP-1, which lies at the junction of its DNA-binding and dimerization domains (basic region and leucine zipper, respectively), as being essential for protein-protein interactions with NFAT in the ternary NFAT/AP-1/DNA complex. In a model of the ternary complex, the segment of NFAT nearest AP-1 is the Rel insert region (RIR), a feature that is notable for its hypervariability in size and in sequence amongst members of the Rel transcription factor family. Here we have used mutational analysis to study the role of the NFAT RIR in binding to DNA and AP-1. Parallel yeast one-hybrid screening assays in combination with alanine-scanning mutagenesis led to the identification of four amino acid residues in the RIR of NFAT2 (also known as NFATC1 or NFATc) that are essential for cooperativity with AP-1 (Ile-544, Glu-545, Thr-551, and Ile-553), and three residues that are involved in interactions with DNA (Lys-538, Arg-540, and Asn-541). These results were confirmed and extended through in vitro binding assays. We thus conclude that the NFAT RIR plays an essential dual role in DNA recognition and cooperative binding to AP-1 family transcription factors.


Mechanisms of deletion formation in Escherichia coli plasmids. II. Deletions mediated by short direct repeats.
A set of plasmids containing 42, 21 and 31 bp direct repeats was used to analyze the effect of repeat length on the frequencies of deletion formation and the structure of the deleted derivatives of different recombination-deficient Escherichia coli strains. Agarose gel electrophoresis of plasmid DNA demonstrated that the formation of deletions in these plasmids was associated with dimerization of plasmid DNA. Restriction analysis of the dimers showed that deletions at short direct repeats arose non-conservatively, that is, the formation of a deletion in one monomeric plasmid unit was not associated with a duplication in the other. Mutations in the recA, recF, recJ and recO genes had no marked effect on either the frequencies of deletion formation or the structure of dimers. In contrast, recB recC mutations greatly increased the frequencies of deletion formation, 6-fold for 42 bp, and 115-fold for 21 bp direct repeats. Conversion of DNA replication to the rolling circle mode in a recB recC strain, resulting in the formation of double-stranded ends, is suggested as the stimulatory effector.