In situ chemichromic studies of interactions between a lutetium bis-octaalkyl-substituted phthalocyanine and selected biological cofactors

This article is available open access through the publisher’s website at the link below. Copyright @ 2011 The Royal Society.Spin-coated films, approximately 100 nm thick, of a newly synthesized bis[octakis(octyl)phthalocyaninato] lutetium(III) complex on ultrasonically cleaned glass substrates exhibit pronounced chemichromic behaviour with potential application in healthcare. In situ kinetic optical absorption spectroscopic measurements show that the phthalocyanine Q-band is red shifted by 60 nm upon oxidation arising from exposure to bromine vapour. Recovery to the original state is achieved by the treatment of the oxidized films with nicotinamide adenine dinucleotide and l-ascorbic acid (vitamin C) in an aqueous solution containing 1.5 M lithium perchlorate. The neutralization process is found to be governed by first-order kinetics. The linear increase of the reduction rate with increasing concentration of cofactors provides a basis for calibration of analyte concentrations ranging from 3.5 mM down to 0.03 mM.Air Force Office of Scientific Research, Air Force Material Command, USAF and the Leverhulme Trust

On Vague Computers

Vagueness is something everyone is familiar with. In fact, most people think that vagueness is closely related to language and exists only there. However, vagueness is a property of the physical world. Quantum computers harness superposition and entanglement to perform their computational tasks. Both superposition and entanglement are vague processes. Thus quantum computers, which process exact data without "exploiting" vagueness, are actually vague computers

A Upf3b-mutant mouse model with behavioral and neurogenesis defects.

Nonsense-mediated RNA decay (NMD) is a highly conserved and selective RNA degradation pathway that acts on RNAs terminating their reading frames in specific contexts. NMD is regulated in a tissue-specific and developmentally controlled manner, raising the possibility that it influences developmental events. Indeed, loss or depletion of NMD factors have been shown to disrupt developmental events in organisms spanning the phylogenetic scale. In humans, mutations in the NMD factor gene, UPF3B, cause intellectual disability (ID) and are strongly associated with autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and schizophrenia (SCZ). Here, we report the generation and characterization of mice harboring a null Upf3b allele. These Upf3b-null mice exhibit deficits in fear-conditioned learning, but not spatial learning. Upf3b-null mice also have a profound defect in prepulse inhibition (PPI), a measure of sensorimotor gating commonly deficient in individuals with SCZ and other brain disorders. Consistent with both their PPI and learning defects, cortical pyramidal neurons from Upf3b-null mice display deficient dendritic spine maturation in vivo. In addition, neural stem cells from Upf3b-null mice have impaired ability to undergo differentiation and require prolonged culture to give rise to functional neurons with electrical activity. RNA sequencing (RNAseq) analysis of the frontal cortex identified UPF3B-regulated RNAs, including direct NMD target transcripts encoding proteins with known functions in neural differentiation, maturation and disease. We suggest Upf3b-null mice serve as a novel model system to decipher cellular and molecular defects underlying ID and neurodevelopmental disorders

Age-related differences in adaptation during childhood: The influences of muscular power production and segmental energy flow caused by muscles

Acquisition of skillfulness is not only characterized by a task-appropriate application of muscular forces but also by the ability to adapt performance to changing task demands. Previous research suggests that there is a different developmental schedule for adaptation at the kinematic compared to the neuro-muscular level. The purpose of this study was to determine how age-related differences in neuro-muscular organization affect the mechanical construction of pedaling at different levels of the task. By quantifying the flow of segmental energy caused by muscles, we determined the muscular synergies that construct the movement outcome across movement speeds. Younger children (5-7 years; n = 11), older children (8-10 years; n = 8), and adults (22-31 years; n = 8) rode a stationary ergometer at five discrete cadences (60, 75, 90, 105, and 120 rpm) at 10% of their individually predicted peak power output. Using a forward dynamics simulation, we determined the muscular contributions to crank power, as well as muscular power delivered to the crank directly and indirectly (through energy absorption and transfer) during the downstroke and the upstroke of the crank cycle. We found significant age × cadence interactions for (1) peak muscular power at the hip joint [Wilks' Lambda = 0.441, F(8,42) = 2.65, p = 0.019] indicating that at high movement speeds children produced less peak power at the hip than adults, (2) muscular power delivered to the crank during the downstroke and the upstroke of the crank cycle [Wilks' Lambda = 0.399, F(8,42) = 3.07, p = 0.009] indicating that children delivered a greater proportion of the power to the crank during the upstroke when compared to adults, (3) hip power contribution to limb power [Wilks' Lambda = 0.454, F(8,42) = 2.54, p = 0.023] indicating a cadence-dependence of age-related differences in the muscular synergy between hip extensors and plantarflexors. The results demonstrate that in spite of a successful performance, children construct the task of pedaling differently when compared to adults, especially when they are pushed to their performance limits. The weaker synergy between hip extensors and plantarflexors suggests that a lack of inter-muscular coordination, rather than muscular power production per se, is a factor that limits children's performance ranges

Sudden Death and Left Ventricular Involvement in Arrhythmogenic Cardiomyopathy

BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) is an inherited heart muscle disorder characterized by myocardial fibrofatty replacement and an increased risk of sudden cardiac death (SCD). Originally described as a right ventricular disease, ACM is increasingly recognized as a biventricular entity. We evaluated pathological, genetic, and clinical associations in a large SCD cohort. METHODS: We investigated 5205 consecutive cases of SCD referred to a national cardiac pathology center between 1994 and 2018. Hearts and tissue blocks were examined by expert cardiac pathologists. After comprehensive histological evaluation, 202 cases (4%) were diagnosed with ACM. Of these, 15 (7%) were diagnosed antemortem with dilated cardiomyopathy (n=8) or ACM (n=7). Previous symptoms, medical history, circumstances of death, and participation in competitive sport were recorded. Postmortem genetic testing was undertaken in 24 of 202 (12%). Rare genetic variants were classified according to American College of Medical Genetics and Genomics criteria. RESULTS: Of 202 ACM decedents (35.4±13.2 years; 82% male), no previous cardiac symptoms were reported in 157 (78%). Forty-one decedents (41/202; 20%) had been participants in competitive sport. The adjusted odds of dying during physical exertion were higher in men than in women (odds ratio, 4.58; 95% CI, 1.54-13.68; P=0.006) and in competitive athletes in comparison with nonathletes (odds ratio, 16.62; 95% CI, 5.39-51.24; P<0.001). None of the decedents with an antemortem diagnosis of dilated cardiomyopathy fulfilled definite 2010 Task Force criteria. The macroscopic appearance of the heart was normal in 40 of 202 (20%) cases. There was left ventricular histopathologic involvement in 176 of 202 (87%). Isolated right ventricular disease was seen in 13%, isolated left ventricular disease in 17%, and biventricular involvement in 70%. Among whole hearts, the most common areas of fibrofatty infiltration were the left ventricular posterobasal (68%) and anterolateral walls (58%). Postmortem genetic testing yielded pathogenic variants in ACM-related genes in 6 of 24 (25%) decedents. CONCLUSIONS: SCD attributable to ACM affects men predominantly, most commonly occurring during exertion in athletic individuals in the absence of previous reported cardiac symptoms. Left ventricular involvement is observed in the vast majority of SCD cases diagnosed with ACM at autopsy. Current Task Force criteria may fail to diagnose biventricular ACM before death

Estimation of Dietary Iron Bioavailability from Food Iron Intake and Iron Status

Currently there are no satisfactory methods for estimating dietary iron absorption (bioavailability) at a population level, but this is essential for deriving dietary reference values using the factorial approach. The aim of this work was to develop a novel approach for estimating dietary iron absorption using a population sample from a sub-section of the UK National Diet and Nutrition Survey (NDNS). Data were analyzed in 873 subjects from the 2000–2001 adult cohort of the NDNS, for whom both dietary intake data and hematological measures (hemoglobin and serum ferritin (SF) concentrations) were available. There were 495 men aged 19–64 y (mean age 42.7±12.1 y) and 378 pre-menopausal women (mean age 35.7±8.2 y). Individual dietary iron requirements were estimated using the Institute of Medicine calculations. A full probability approach was then applied to estimate the prevalence of dietary intakes that were insufficient to meet the needs of the men and women separately, based on their estimated daily iron intake and a series of absorption values ranging from 1–40%. The prevalence of SF concentrations below selected cut-off values (indicating that absorption was not high enough to maintain iron stores) was derived from individual SF concentrations. An estimate of dietary iron absorption required to maintain specified SF values was then calculated by matching the observed prevalence of insufficiency with the prevalence predicted for the series of absorption estimates. Mean daily dietary iron intakes were 13.5 mg for men and 9.8 mg for women. Mean calculated dietary absorption was 8% in men (50th percentile for SF 85 µg/L) and 17% in women (50th percentile for SF 38 µg/L). At a ferritin level of 45 µg/L estimated absorption was similar in men (14%) and women (13%). This new method can be used to calculate dietary iron absorption at a population level using data describing total iron intake and SF concentration

Characteristics of outdoor falls among older people: A qualitative study

Background Falls are a major threat to older people’s health and wellbeing. Approximately half of falls occur in outdoor environments but little is known about the circumstances in which they occur. We conducted a qualitative study to explore older people’s experiences of outdoor falls to develop understanding of how they may be prevented. Methods We conducted nine focus groups across the UK (England, Wales, and Scotland). Our sample was from urban and rural settings and different environmental landscapes. Participants were aged 65+ and had at least one outdoor fall in the past year. We analysed the data using framework and content analyses. Results Forty-four adults aged 65 – 92 took part and reported their experience of 88 outdoor falls. Outdoor falls occurred in a variety of contexts, though reports suggested the following scenarios may have been more frequent: when crossing a road, in a familiar area, when bystanders were around, and with an unreported or unknown attribution. Most frequently, falls resulted in either minor or moderate injury, feeling embarrassed at the time of the fall, and anxiety about falling again. Ten falls resulted in fracture, but no strong pattern emerged in regard to the contexts of these falls. Anxiety about falling again appeared more prevalent among those that fell in urban settings and who made more visits into their neighbourhood in a typical week. Conclusions This exploratory study has highlighted several aspects of the outdoor environment that may represent risk factors for outdoor falls and associated fear of falling. Health professionals are recommended to consider outdoor environments as well as the home setting when working to prevent falls and increase mobility among older people

Risk factors for high anti-HHV-8 antibody titers (≥1:51,200) in black, HIV-1 negative South African cancer patients: a case control study

Background: Infection with human herpesvirus 8 (HHV-8) is the necessary causal agent in the development of Kaposi's sarcoma (KS). Infection with HIV-1, male gender and older age all increase risk for KS. However, the geographic distribution of HHV-8 and KS both prior to the HIV/AIDS epidemic and with HIV/AIDS suggest the presence of an additional co-factor in the development of KS. Methods: Between January 1994 and October 1997, we interviewed 2576 black in-patients with cancer in Johannesburg and Soweto, South Africa. Blood was tested for antibodies against HIV-1 and HHV-8 and the study was restricted to 2191 HIV-1 negative patients. Antibodies against the latent nuclear antigen of HHV-8 encoded by orf73 were detected with an indirect immunofluorescence assay. We examined the relationship between high anti-HHV-8 antibody titers (≥1:51,200) and sociodemographic and behavioral factors using unconditional logistic regression models. Variables that were significant at p = 0.10 were included in multivariate analysis. Results: Of the 2191 HIV-1 negative patients who did not have Kaposi's sarcoma, 854 (39.0%) were positive for antibodies against HHV-8 according to the immunofluorescent assay. Among those seropositive for HHV-8, 530 (62.1%) had low titers (1:200), 227 (26.6%) had medium titers (1:51,200) and 97 (11.4%) had highest titers (1:204,800). Among the 2191 HIV-1 negative patients, the prevalence of high anti-HHV-8 antibody titers (≥1:51,200) was independently associated with increasing age (ptrend = 0.04), having a marital status of separated or divorced (p = 0.003), using wood, coal or charcoal as fuel for cooking 20 years ago instead of electricity (p = 0.02) and consuming traditional maize beer more than one time a week (p = 0.02; p-trend for increasing consumption = 0.05) although this may be due to chance given the large number of predictors considered in this analysis. Conclusions: Among HIV-negative subjects, patients with high anti-HHV-8 antibody titers are characterized by older age. Other associations that may be factors in the development of high anti- HHV-8 titers include exposure to poverty or a low socioeconomic status environment and consumption of traditional maize beer. The relationship between these variables and high anti- HHV-8 titers requires further, prospective study