Ferritins: furnishing proteins with iron

Ferritins are a superfamily of iron oxidation, storage and mineralization proteins found throughout the animal, plant, and microbial kingdoms. The majority of ferritins consist of 24 subunits that individually fold into 4-α-helix bundles and assemble in a highly symmetric manner to form an approximately spherical protein coat around a central cavity into which an iron-containing mineral can be formed. Channels through the coat at inter-subunit contact points facilitate passage of iron ions to and from the central cavity, and intrasubunit catalytic sites, called ferroxidase centers, drive Fe2+ oxidation and O2 reduction. Though the different members of the superfamily share a common structure, there is often little amino acid sequence identity between them. Even where there is a high degree of sequence identity between two ferritins there can be major differences in how the proteins handle iron. In this review we describe some of the important structural features of ferritins and their mineralized iron cores and examine in detail how three selected ferritins oxidise Fe2+ in order to explore the mechanistic variations that exist amongst ferritins. We suggest that the mechanistic differences reflect differing evolutionary pressures on amino acid sequences, and that these differing pressures are a consequence of different primary functions for different ferritins

Developing and implementing an integrated delirium prevention system of care:a theory driven, participatory research study

Background: Delirium is a common complication for older people in hospital. Evidence suggests that delirium incidence in hospital may be reduced by about a third through a multi-component intervention targeted at known modifiable risk factors. We describe the research design and conceptual framework underpinning it that informed the development of a novel delirium prevention system of care for acute hospital wards. Particular focus of the study was on developing an implementation process aimed at embedding practice change within routine care delivery. Methods: We adopted a participatory action research approach involving staff, volunteers, and patient and carer representatives in three northern NHS Trusts in England. We employed Normalization Process Theory to explore knowledge and ward practices on delirium and delirium prevention. We established a Development Team in each Trust comprising senior and frontline staff from selected wards, and others with a potential role or interest in delirium prevention. Data collection included facilitated workshops, relevant documents/records, qualitative one-to-one interviews and focus groups with multiple stakeholders and observation of ward practices. We used grounded theory strategies in analysing and synthesising data. Results: Awareness of delirium was variable among staff with no attention on delirium prevention at any level; delirium prevention was typically neither understood nor perceived as meaningful. The busy, chaotic and challenging ward life rhythm focused primarily on diagnostics, clinical observations and treatment. Ward practices pertinent to delirium prevention were undertaken inconsistently. Staff welcomed the possibility of volunteers being engaged in delirium prevention work, but existing systems for volunteer support were viewed as a barrier. Our evolving conception of an integrated model of delirium prevention presented major implementation challenges flowing from minimal understanding of delirium prevention and securing engagement of volunteers alongside practice change. The resulting Prevention of Delirium (POD) Programme combines a multi-component delirium prevention and implementation process, incorporating systems and mechanisms to introduce and embed delirium prevention into routine ward practices. Conclusions: Although our substantive interest was in delirium prevention, the conceptual and methodological strategies pursued have implications for implementing and sustaining practice and service improvements more broadly

A Neural Network for Stance Phase detection in smart cane users

Slides from conferencePersons with disabilities often rely on assistive devices to carry on their Activities of Daily Living. Deploying sensors on these devices may provide continuous valuable knowledge on their state and condition. Canes are among the most frequently used assistive devices, regularly employed for ambulation by persons with pain on lower limbs and also for balance. Load on canes is reportedly a meaningful condition indicator. Ideally, it corresponds to the time cane users support weight on their lower limb (stance phase). However, in reality, this relationship is not straightforward. We present a Multilayer Perceptron to reliably predict the Stance Phase in cane users using a simple support detection module on commercial canes. The system has been successfully tested on five cane users in care facilities in Spain. It has been optimized to run on a low cost microcontroller.This work has been supported by: Proyectos Puente and programa operativo de empleo juvenil (UMAJI58) and Plan Propio de Investigación at University of Malaga and the Swedish Knowledge Foundation (KKS) through the research profile Embedded Sensor Systems for Health (ESS−H) at Malardalen University, Sweden. Authors would like to ac- knowledge PONIENTE and LOS NARANJOS senior centers for their support during the tests. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

The Absolute of Advaita and the Spirit of Hegel: Situating Vedānta on the Horizons of British Idealisms

$\textit{Purpose}$ A significant volume of philosophical literature produced by Indian academic philosophers in the first half of the twentieth century can be placed under the rubric of ‘Śaṁkara and X’, where X is Hegel, or a German or a British philosopher who had commented on, elaborated or critiqued the Hegelian system. We will explore in this essay the philosophical significance of Hegel-influenced systems as an intellectual conduit for these Indo-European conceptual encounters, and highlight how for some Indian philosophers the British variations on Hegelian systems were both a point of entry into debates over ‘idealism’ and ‘realism’ in contemporary European philosophy and an occasion for defending Advaita against the charge of propounding a doctrine of world illusionism. $\textit{Methodology}$ Our study of the philosophical enquiries of A.C. Mukerji, P.T. Raju, and S.N.L. Shrivastava indicates that they developed distinctive styles of engaging with Hegelian idealisms as they reconfigured certain aspects of the classical Advaita of Śaṁkara through contemporary vocabulary. $\textit{Result and Conclusion}$ These appropriations of Hegelian idioms can be placed under three overlapping styles: (a) Mukerji was partly involved in locating Advaita in an intermediate conceptual space between, on the one hand, Kantian agnosticism and, on the other hand, Hegelian absolutism; (b) Raju and Shrivastava presented Advaitic thought as the fulfilment of certain insights of Hegel and F.H. Bradley; and (c) the interrogations of Hegel’s ‘idealism’ provided several Indian academic philosophers with a hermeneutic opportunity to revisit the vexed question of whether the ‘idealism’ of Śaṁkara reduces the phenomenal world, structured by $\textit{māyā}$, to a bundle of ideas

Hospital Performance, the Local Economy, and the Local Workforce: Findings from a US National Longitudinal Study

Blustein and colleagues examine the associations between changes in hospital performance and their local economic resources. Locationally disadvantaged hospitals perform poorly on key indicators, raising concerns that pay-for-performance models may not reduce inequality

The expression of p53-induced protein with death domain (Pidd) and apoptosis in oral squamous cell carcinoma

The Pidd (p53-induced protein with death domain) gene was shown to be induced by the tumour suppressor p53 and to mediate p53-dependent apoptosis in mouse and human cells, through interactions with components of both the mitochondrial and the death receptor signalling pathways. To study the role of Pidd in clinical tumours, we measured its expression by quantitative reverse transcription-PCR in microdissected oral squamous cell carcinomas (OSCC) with and without p53 mutation. Tumour cell apoptosis was assessed by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling. Tumour proliferation was assessed by immunohistochemical staining for the Ki-67 antigen. We found a wide range of Pidd expression among OSCC. Statistical analysis revealed an association between Pidd expression and apoptotic index (Mann–Whitney test, P<0.001), consistent with a role of Pidd in apoptosis in this tumour type. Furthermore, we showed a positive correlation between apoptotic index and proliferative index that has not been previously described for OSCC. There was no correlation between Pidd expression and the p53 mutation status of these tumours, suggesting that Pidd expression may be regulated by p53-independent mechanisms. Further characterisation of these molecular defects in the control of proliferation and apoptosis should help in developing treatments that target OSCC according to their biological properties

Chimpanzee APOBEC3 proteins deter SIVs from any monkey business

Cross-species transmissions of viruses from animals to humans are at the origin of major human pathogenic viruses. While the role of ecological and epidemiological factors in the emergence of new pathogens is well documented, the importance of host factors is often unknown. Chimpanzees are the closest relatives of humans and the animal reservoir at the origin of the human AIDS pandemic. However, despite being regularly exposed to monkey lentiviruses through hunting, chimpanzees are naturally infected by only a single simian immunodeficiency virus, SIVcpz. Here, we asked why chimpanzees appear to be protected against the successful emergence of other SIVs. In particular, we investigated the role of the chimpanzee APOBEC3 genes in providing a barrier to infection by most monkey lentiviruses. We found that most SIV Vifs, including Vif from SIVwrc infecting western-red colobus, the chimpanzee's main monkey prey in West Africa, could not antagonize chimpanzee APOBEC3G. Moreover, chimpanzee APOBEC3D, as well as APOBEC3F and APOBEC3H, provided additional protection against SIV Vif antagonism. Consequently, lentiviral replication in primary chimpanzee CD4(+) T cells was dependent on the presence of a lentiviral vif gene that could antagonize chimpanzee APOBEC3s. Finally, by identifying and functionally characterizing several APOBEC3 gene polymorphisms in both common chimpanzees and bonobos, we found that these ape populations encode APOBEC3 proteins that are uniformly resistant to antagonism by monkey lentiviruses

A New Model of Delirium Care in the Acute Geriatric Setting: Geriatric Monitoring Unit

<p>Abstract</p> <p>Background</p> <p>Delirium is a common and serious condition, which affects many of our older hospitalised patients. It is an indicator of severe underlying illness and requires early diagnosis and prompt treatment, associated with poor survival, functional outcomes with increased risk of institutionalisation following the delirium episode in the acute care setting. We describe a new model of delirium care in the acute care setting, titled Geriatric Monitoring Unit (GMU) where the important concepts of delirium prevention and management are integrated. We hypothesize that patients with delirium admitted to the GMU would have better clinical outcomes with less need for physical and psychotropic restraints compared to usual care.</p> <p>Methods/Design</p> <p>GMU models after the Delirium Room with adoption of core interventions from Hospital Elder Life Program and use of evening bright light therapy to consolidate circadian rhythm and improve sleep in the elderly patients. The novelty of this approach lies in the amalgamation of these interventions in a multi-faceted approach in acute delirium management. GMU development thus consists of key considerations for room design and resource planning, program specific interventions and daily core interventions. Assessments undertaken include baseline demographics, comorbidity scoring, duration and severity of delirium, cognitive, functional measures at baseline, 6 months and 12 months later. Additionally we also analysed the pre and post-GMU implementation knowledge and attitude on delirium care among staff members in the geriatric wards (nurses, doctors) and undertook satisfaction surveys for caregivers of patients treated in GMU.</p> <p>Discussion</p> <p>This study protocol describes the conceptualization and implementation of a specialized unit for delirium management. We hypothesize that such a model of care will not only result in better clinical outcomes for the elderly patient with delirium compared to usual geriatric care, but also improved staff knowledge and satisfaction. The model may then be transposed across various locations and disciplines in the acute hospital where delirious patients could be sited.</p> <p>Trial Registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN52323811">ISRCTN52323811</a></p

The Relationship between Urinary Renin Angiotensin System Markers, Renal and Vascular Function in Adolescents with Type 1 Diabetes

AIMS: The relationship between the renal renin-angiotensin aldosterone system (RAAS) and cardiorenal pathophysiology is unclear. Our aims were to assess (1) levels of urinary RAAS components and (2) the association between RAAS components and HbA1c, urine albumin/creatinine ratio (ACR), estimated glomerular filtration rate (eGFR) and blood pressure in otherwise healthy adolescents with type 1 diabetes mellitus (TID) vs. healthy controls (HC). METHODS: Urinary angiotensinogen and ACE2 levels, activity of ACE and ACE2, blood pressure (BP), HbA1c, ACR and eGFR were measured in 65 HC and 194 T1D from the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT). RESULTS: Urinary levels of all RAAS components were higher in T1D vs. HC (p<0.0001). Higher HbA1c was associated with higher urinary angiotensinogen, ACE2, and higher activity of ACE and ACE2 (p<0.0001, p=0.0003, p=0.003 and p=0.007 respectively) in T1D. Higher ACR (within the normal range) was associated with higher urinary angiotensinogen (p<0.0001) and ACE activity (p=0.007), but not with urinary ACE2 activity or ACE2 levels. These observations were absent in HC. Urinary RAAS components were not associated with BP or eGFR in T1D or HC. CONCLUSIONS: Otherwise healthy adolescents with T1D exhibit higher levels of urinary RAAS components compared to HC. While levels of all urinary RAAS components correlate with HbA1c in T1D, only urinary angiotensinogen and ACE activity correlate with ACR, suggesting that these factors reflect an intermediary pathogenic link between hyperglycemia and albuminuria within the normal range