Development of the Variable Dexterity Test: construction, reliability and validity

Background/Aims: This article introduces a dexterity test designed to assess individual types of dexterity used to carry out activities of daily living (ADL). The Variable Dexterity Test (VDT) was developed as part of a wider study, the broader aim being to fully understand dexterity and its effect on human-product interaction during ADL. This was done with a view to improve occupational therapy methods when assessing dexterity and general hand function. Methods: The control group consisted of 24 healthy participants. Estimates of reliability and validity were evaluated in this pilot study. Inter-rater and test-retest reliability were assessed using a one-way ANOVA. The validity of the test was estimated by correlating participants’ VDT scores with their proficiency to complete four ADL task actions and a standardised dexterity test (Purdue Pegboard Test). Results: The test produced consistent results among the control group with both a single assessor (test‑retest reliability) and multiple assessors (inter‑rater reliability). High correlations between participants’ VDT scores and proficiency to perform ADL were found for most of the subtests. There was also a high correlation between participants’ scores from the Purdue Pegboard Test and the VDT. Conclusions: The VDT proved to be a flexible, reliable and valid tool that assesses dexterity based on ability to carry out ADL. Validity and reliability estimates show encouraging values, which recognises that the VDT can be used as an accurate method to assess more than one type of dexterity.</p

Survey of the needs of patients with spinal cord injury: impact and priority for improvement in hand function in tetraplegics\ud

Objective: To investigate the impact of upper extremity deficit in subjects with tetraplegia.\ud \ud Setting: The United Kingdom and The Netherlands.\ud \ud Study design: Survey among the members of the Dutch and UK Spinal Cord Injury (SCI) Associations.\ud \ud Main outcome parameter: Indication of expected improvement in quality of life (QOL) on a 5-point scale in relation to improvement in hand function and seven other SCI-related impairments.\ud \ud Results: In all, 565 subjects with tetraplegia returned the questionnaire (overall response of 42%). Results in the Dutch and the UK group were comparable. A total of 77% of the tetraplegics expected an important or very important improvement in QOL if their hand function improved. This is comparable to their expectations with regard to improvement in bladder and bowel function. All other items were scored lower.\ud \ud Conclusion: This is the first study in which the impact of upper extremity impairment has been assessed in a large sample of tetraplegic subjects and compared to other SCI-related impairments that have a major impact on the life of subjects with SCI. The present study indicates a high impact as well as a high priority for improvement in hand function in tetraplegics.\ud \u

Functional Interactions between the erupted/tsg101 Growth Suppressor Gene and the DaPKC and rbf1 Genes in Drosophila Imaginal Disc Tumors

BACKGROUND: The Drosophila gene erupted (ept) encodes the fly homolog of human Tumor Susceptibility Gene-101 (TSG101), which functions as part of the conserved ESCRT-1 complex to facilitate the movement of cargoes through the endolysosomal pathway. Loss of ept or other genes that encode components of the endocytic machinery (e.g. synatxin7/avalanche, rab5, and vps25) produces disorganized overgrowth of imaginal disc tissue. Excess cell division is postulated to be a primary cause of these 'neoplastic' phenotypes, but the autonomous effect of these mutations on cell cycle control has not been examined. PRINCIPAL FINDINGS: Here we show that disc cells lacking ept function display an altered cell cycle profile indicative of deregulated progression through the G1-to-S phase transition and express reduced levels of the tumor suppressor ortholog and G1/S inhibitor Rbf1. Genetic reductions of the Drosophila aPKC kinase (DaPKC), which has been shown to promote tumor growth in other fly tumor models, prevent both the ept neoplastic phenotype and the reduction in Rbf1 levels that otherwise occurs in clones of ept mutant cells; this effect is coincident with changes in localization of Notch and Crumbs, two proteins whose sorting is altered in ept mutant cells. The effect on Rbf1 can also be blocked by removal of the gamma-secretase component presenilin, suggesting that cleavage of a gamma-secretase target influences Rbf1 levels in ept mutant cells. Expression of exogenous rbf1 completely ablates ept mutant eye tissues but only mildly affects the development of discs composed of cells with wild type ept. CONCLUSIONS: Together, these data show that loss of ept alters nuclear cell cycle control in developing imaginal discs and identify the DaPKC, presenilin, and rbf1 genes as modifiers of molecular and cellular phenotypes that result from loss of ept

Polymorphism in the oxytocin promoter region in patients with lactase non-persistence is not related to symptoms

<p>Abstract</p> <p>Background</p> <p>Oxytocin and the oxytocin receptor have been demonstrated in the gastrointestinal (GI) tract and have been shown to exert physiological effects on gut motility. The role for oxytocin in the pathophysiology of GI complaints is unknown. The aim of this study was to examine genetic variations or polymorphism of oxytocin (<it>OXT</it>) and its receptor (<it>OXTR</it>) genes in patients with GI complaints without visible organic abnormalities.</p> <p>Methods</p> <p>Genetic variants in the <it>OXT </it>promoter region, and in the <it>OXTR </it>gene in DNA samples from 131 rigorously evaluated patients with Irritable Bowel Syndrome (IBS), 408 homozygous subjects referred for lactase (LCT-13910 C>T, rs4988235) genotyping, and 299 asymptomatic blood donors were compared. One polymorphism related to the <it>OXT </it>gene (rs6133010 A>G) and 4 related to the <it>OXTR </it>gene (rs1465386 G>T, rs3806675 G>A, rs968389 A>G, rs1042778 G>T) were selected for genotyping using Applied Biosystems 7900 HT allele discrimination assays.</p> <p>Results</p> <p>There were no statistically significant differences in the genotype or allele frequencies in any of the SNPs when IBS patients were compared to healthy controls. Among subjects referred for lactase genotyping, the rs6133010 A>G <it>OXT </it>promoter A/G genotype tended to be more common in the 154 non-persistent (27.3%) subjects than in the 254 lactase persistant (18.1%) subjects and in the healthy controls (19.4%) (p = 0.08). When direct comparing, the A/G genotype was less common in the <it>OXT </it>promoter region in controls (p = 0.09) and in subjects with lactase persistence (p = 0.03) compared to subjects with lactase non-persistence. When healthy controls were viewed according to their own LCT-13910 genotypes, the C/C lactase non-persistent controls had a higher frequency for the <it>OXT </it>promoter A/G genotype than LCT-13910 T/T lactase persistent controls (41.2% vs 13.1%).</p> <p>No significant differences in frequencies of the investigated <it>OXTR </it>SNPs were noted in this study.</p> <p>Conclusion</p> <p>The results suggest that polymorphism in the promoter region of the <it>OXT </it>gene is most common in subjects with lactase non-persistence. This polymorphism may not be related to GI symptoms, as it is related to lactase non-persistence also in healthy controls.</p

'Tipping the Balance': Karl Friedrich Meyer, Latent Infections, and the Birth of Modern Ideas of Disease Ecology

The Swiss-born medical researcher Karl Friedrich Meyer (1884–1974) is best known as a ‘microbe hunter’ who pioneered investigations into diseases at the intersection of animal and human health in California in the 1920s and 1930s. In particular, historians have singled out Meyer’s 1931 Ludwig Hektoen Lecture in which he described the animal kingdom as a ‘reservoir of disease’ as a forerunner of ‘one medicine’ approaches to emerging zoonoses. In so doing, however, historians risk overlooking Meyer’s other intellectual contributions. Developed in a series of papers from the mid-1930s onwards, these were ordered around the concept of latent infections and sought to link microbial behavior to broader bio-ecological, environmental, and social factors that impact hostpathogen interactions. In this respect Meyer—like the comparative pathologist Theobald Smith and the immunologist Frank Macfarlane Burnet—can be seen as a pioneer of modern ideas of disease ecology. However, while Burnet’s and Smith’s contributions to this scientific field have been widely acknowledged, Meyer’s have been largely ignored. Drawing on Meyer’s published writings and private correspondence, this paper aims to correct that lacuna while contributing to a reorientation of the historiography of bacteriological epidemiology. In particular I trace Meyer’s intellectual exchanges with Smith, Burnet and the animal ecologist Charles Elton, over brucellosis, psittacosis and plague—exchanges that not only showed how environmental and ecological conditions could ‘tip the balance’ in favor of parasites but which transformed Meyer thinking about resistance to infection and disease

Potent Anti-Tumor Effect Generated by a Novel Human Papillomavirus (HPV) Antagonist Peptide Reactivating the pRb/E2F Pathway

Human papillomavirus type 16 (HPV16) E7 is a viral oncoprotein believed to play a major role in cervical cancer. In this study, an antagonist peptide against HPV16E7 protein was first identified from screening the c7c phage display peptide library. The binding specificity and affinity of the selected peptide to HPV16E7 were tested by competitive enzyme-linked immunosorbent assay (ELISA). The antagonist peptide showed obvious anti-tumor efficacy both in cell lines and animal tumor models. Significant cell proliferation inhibition with high specificity was noted when HPV16-positive cells were treated with the peptide. This anti-tumor efficacy was resulted from overriding the activities of HPV16E7 and reactivating the pRb/E2F pathway, as shown by a series of experiments. Flow cytometry analysis revealed that the selected peptide induced G1 arrest in a dose-dependent manner. Competitive ELISA, pull down, and Co-IP experiments indicated that the selected peptide disrupted the interaction between HPV16E7 and pRb proteins both in vitro and in vivo. Luciferase reporter assay verified that transcription activities of E2F were suppressed by the peptide through restoration of pRb. RT-PCR and Western blot revealed that it reduced cyclins A, D1, and E1 expression, and led to HPV16E7 protein degradation, but pRb protein stabilization. The current study suggests that this specific peptide may serve as a potential therapeutic agent for HPV16-positive cervical cancer

Olfactory discrimination predicts cognitive decline among community-dwelling older adults

The presence of olfactory dysfunction in individuals at higher risk of Alzheimer's disease has significant diagnostic and screening implications for preventive and ameliorative drug trials. Olfactory threshold, discrimination and identification can be reliably recorded in the early stages of neurodegenerative diseases. The current study has examined the ability of various olfactory functions in predicting cognitive decline in a community-dwelling sample. A group of 308 participants, aged 46–86 years old, were recruited for this study. After 3 years of follow-up, participants were divided into cognitively declined and non-declined groups based on their performance on a neuropsychological battery. Assessment of olfactory functions using the Sniffin' Sticks battery indicated that, contrary to previous findings, olfactory discrimination, but not olfactory identification, significantly predicted subsequent cognitive decline (odds ratio=0.869; P<0.05; 95% confidence interval=0.764−0.988). The current study findings confirm previously reported associations between olfactory and cognitive functions, and indicate that impairment in olfactory discrimination can predict future cognitive decline. These findings further our current understanding of the association between cognition and olfaction, and support olfactory assessment in screening those at higher risk of dementia

A falling of the veils: turning points and momentous turning points in leadership and the creation of CSR

This article uses the life stories approach to leadership and leadership development. Using exploratory, qualitative data from a Forbes Global 2000 and FTSE 100 company, we discuss the role of the turning point (TP) as an important antecedent of leadership in corporate social responsibility. We argue that TPs are causally efficacious, linking them to the development of life narratives concerned with an evolving sense of personal identity. Using both a multi-disciplinary perspective and a multi-level focus on CSR leadership, we identify four narrative cases. We propose that they helped to re-define individuals’ sense of self and in some extreme cases completely transformed their self-identity as leaders of CSR. Hence we also distinguish the momentous turning point (MTP) that created a seismic shift in personality, through re-evaluation of the individuals’ personal values. We argue that whilst TPs are developmental experiences that can produce responsible leadership, the MTP changes the individuals’ personal priorities in life to produce responsible leadership that perhaps did not exist previously. Thus we appropriate Maslow’s (1976, p. 77) metaphorical phrase ‘A falling of the veils’ from his discussion of peak and desolation experiences that produce personal growth. Using a multi-disciplinary literature from social theory (Archer, 2012) moral psychology (Narvaez, 2009) and social psychology (Schwartz, 2010), we present a theoretical model that illustrates the psychological process of the (M)TP, thus contributing to the growing literature on the microfoundations of CSR