How cancer doctors use personalized medicine to target variations unique to each tumour

The Children’s Cancer Institute in Sydney recently launched an ambitious program. From early next year, scientists will analyse the unique cancer cells of 12 children diagnosed with the most aggressive forms of the disease to find the best treatment for each child. By 2020, they aim to have these individualised treatment options available to all children diagnosed with cancers that have a less than 30% survival rate. This way of tailoring treatment to each person is known as personalised medicine, and advances in DNA sequencing have paved the way for a new era in cancer management.

Specific language impairment in pre-adolescence, adolescence, and adulthood with special emphasis on health-related quality of life

This clinical study focused on effects of childhood specific language impairment (SLI) on daily functioning in late life. SLI is a neurobiological disorder with genetic predisposition and manifests as poor language production or comprehension or both in a child with age-level non-verbal intelligence and no other known cause for deficient language development. The prevalence rate of around 7% puts it among the most prevalent developmental disorders in childhood. Negative long-term effects, such as problems in learning and behavior, are frequent. In follow-up studies the focus has seldom been on self-perception of daily functioning and participation, which are considered important in the International Classification of Functioning, Disability, and Health (ICF). To investigate the self-perceived aspects of everyday functioning in individuals with childhood receptive SLI compared with age- and gender-matched control populations, the 15D, 16D, and 17D health-related quality of life (HRQoL) questionnaires were applied. These generic questionnaires include 15, 16, and 17 dimensions, respectively, and give both a single index score and a profile with values on each dimension. Information on different life domains (rehabilitation, education, employment etc.) from each age-group was collected with separate questionnaires. The study groups comprised adults, adolescents (12-16 years), and pre-adolescents (8-11 years) who had received a diagnosis of receptive SLI and had been examined, usually before school age, at the Department of Phoniatrics of Helsinki University Central Hospital, where children with language deficits caused by various etiologies are examined and treated by a multidisciplinary team. The adult respondents included 33 subjects with a mean age of 34 years. Measured with 15D, the subjects perceived their HRQoL to be nearly as good as that of their controls, but on the dimensions of speech, usual activities, mental functioning, and distress they were significantly worse off. They significantly more often lived with their parents (19%) or were pensioned (26%) than the adult Finnish population on average. Adults with self-perceived problems in finding words and in remembering instructions, manifestations of persistent language impairment, showed inferior every day functioning to the rest of the study group. Of the adolescents and pre-adolescents, 48 and 51, respectively, responded. The majority in both groups had received special education or extra educational support at school. They all had attended speech therapy at some point; at the time of the study only one adolescent, but every third pre-adolescent still received speech therapy. The 16D score of the adolescent or the 17D score of the pre-adolescents did not differ from that of their controls. The 16D profiles differed on some dimensions; subjects were significantly worse off on the dimension of mental functioning, but better off on the dimension of vitality than controls. Of the 17D dimensions, the study group was significantly worse off on speech, whereas the control group reported significantly more problems in sleeping. Of the childhood performance measures investigated, low verbal intelligence quotient (VIQ), which is often considered to reflect receptive language impairment, was in adults subjects significantly associated with some of the self-perceived problems, such as problems in usual activities and mental functioning. The 15D, 16D, and 17D questionnaires served well in measuring self-perceived HRQoL. Such standardized measures with population values are especially important in confirming with the ICF guidelines. In the future these questionnaires could perhaps be used on a more individual level in follow-up of children in clinics, and even in special schools and classes, to detect those children at greatest risk of negative long-term effects and perhaps diminished well-being regarding daily functioning and participation.

Western medicine and Australian Indigenous healing practices

Most projects undertaken by government health organisations are formulated on values and beliefs about health and illness that are derived from Anglo/Celtic culture. Health beliefs differ between cultures and it has been identified that the differences in the Indigenous and non-Indigenous constructs of health impacts negatively on the effectiveness of mainstream healthcare provided to Indigenous peoples [2]. This implies that strategies that incorporate, or better still are derived from, Indigenous health beliefs have a greater potential to be effective. This article introduces a prospective survey project asking how western medicine and traditional treatments interface with each other.

Problem-based learning in an e-learning environment: A case study at Griffith University School of Medicine

Increasing numbers of medical schools in Australia and overseas have moved away from didactic teaching methodologies and embraced problem-based learning (PBL) to improve clinical reasoning skills and communication skills as well as to encourage self-directed lifelong learning. In January 2005, the first cohort of students entered the new MBBS program at the Griffith University School of Medicine, Gold Coast, to embark upon an exciting, fully integrated curriculum using PBL, combining electronic delivery, communication and evaluation systems incorporating cognitive principles that underpin the PBL process. This chapter examines the educational philosophies and design of the e-learning environment underpinning the processes developed to deliver, monitor and evaluate the curriculum. Key initiatives taken to promote student engagement and innovative and distinctive approaches to student learning at Griffith promoted within the conceptual model for the curriculum are (a) Student engagement, (b) Pastoral care, (c) Staff engagement, (d) Monitoring and (e) Curriculum/Program Review. © 2007 Springer-Verlag Berlin Heidelberg.

Social Networks and Everyday Practices in Russia

My doctoral dissertation in sociology and Russian studies, Social Networks and Everyday Practices in Russia, employs a "micro" or "grassroots" perspective on the transition. The study is a collection of articles detailing social networks in five different contexts. The first article examines Russian birthdays from a network perspective. The second takes a look at health care to see whether networks have become obsolete in a sector that is still overwhelmingly public, but increasingly being monetarised. The third article investigates neighbourhood relations. The fourth details relationships at work, particularly from the vantage point of internal migration. The fifth explores housing and the role of networks and money both in the Soviet and post-Soviet era. The study is based on qualitative social network and interview data gathered among three groups, teachers, doctors and factory workers, in St. Petersburg during 1993-2000. Methodologically it builds on a qualitative social network approach. The study adds a critical element to the discussion on networks in post-socialism. A considerable consensus exists that social networks were vital in state socialist societies and were used to bypass various difficulties caused by endemic shortages and bureaucratic rigidities, but a more debated issue has been their role in post-socialism. Some scholars have argued that the importance of networks has been dramatically reduced in the new market economy, whereas others have stressed their continuing importance. If a common denominator in both has been a focus on networks in relation to the past, a more overlooked aspect has been the question of inequality. To what extent is access to networks unequally distributed? What are the limits and consequences of networks, for those who have access, those outside networks or society at large? My study provides some evidence about inequalities. It shows that some groups are privileged over others, for instance, middle-class people in informal access to health care. Moreover, analysing the formation of networks sheds additional light on inequalities, as it highlights the importance of migration as a mechanism of inequality, for example. The five articles focus on how networks are actually used in everyday life. The article on health care, for instance, shows that personal connections are still important and popular in post-Soviet Russia, despite the growing importance of money and the emergence of "fee for service" medicine. Fifteen of twenty teachers were involved in informal medical exchange during a two-week study period, so that they used their networks to bypass the formal market mechanisms or official procedures. Medicines were obtained through personal connections because some were unavailable at local pharmacies or because these connections could provide medicines for a cheaper price or even for free. The article on neighbours shows that "mutual help" was the central feature of neighbouring, so that the exchange of goods, services and information covered almost half the contacts with neighbours reported. Neighbours did not provide merely small-scale help but were often exchange partners because they possessed important professional qualities, had access to workplace resources, or knew somebody useful. The article on the Russian work collective details workplace-related relationships in a tractor factory and shows that interaction with and assistance from one's co-workers remains important. The most interesting finding was that co-workers were even more important to those who had migrated to the city than to those who were born there, which is explained by the specifics of Soviet migration. As a result, the workplace heavily influenced or absorbed contexts for the worker migrants to establish relationships whereas many meeting-places commonly available in Western countries were largely absent or at least did not function as trusted public meeting places to initiate relationships. More results are to be found from my dissertation: Anna-Maria Salmi: Social Networks and Everyday Practices in Russia, Kikimora Publications, 2006, see www.kikimora-publications.com.

G.W. Leibniz and Scientific Societies

The famous philosopher Leibniz (1646-1716) was also active in the (cultural) politics of his time. His interest in forming scientific societies never waned and his efforts led to the founding of the Berlin Academy of Sciences. He also played a part in the founding of the Dresden Academy of Science and the St. Petersburg Academy of Science. Though Leibniz's models for the scientific society were the Royal Society and the Royal Science Academy of France, his pansophistic vision of scientific cooperation sometimes took on utopian dimensions. In this paper, I will present Leibniz's ideas of scientific cooperation as a kind of religious activity and discuss his various schemes for the founding of such scientific societies.

Choosing an appropriate index to construct dominance hierarchies in animal societies: a comparison of three indices

A plethora of indices have been proposed and used to construct dominance hierarchies in a variety of vertebrate and invertebrate societies, although the rationale for choosing a particular index for a particular species is seldom explained. In this study, we analysed and compared three such indices, viz Clutton-Brock et al.'s index (CBI), originally developed for red deer, Cervus elaphus, David's score (DS) originally proposed by the statistician H. A. David and the frequency-based index of dominance (FDI) developed and routinely used by our group for the primitively eusocial wasps Ropalidia marginata and Ropalidia cyathiformis. Dominance ranks attributed by all three indices were strongly and positively correlated for both natural data sets from the wasp colonies and for artificial data sets generated for the purpose. However, the indices differed in their ability to yield unique (untied) ranks in the natural data sets. This appears to be caused by the presence of noninteracting individuals and reversals in the direction of dominance in some of the pairs in the natural data sets. This was confirmed by creating additional artificial data sets with noninteracting individuals and with reversals. Based on the criterion of yielding the largest proportion of unique ranks, we found that FDI is best suited for societies such as the wasps belonging to Ropalidia, DS is best suited for societies with reversals and CBI remains a suitable index for societies such as red deer in which multiple interactions are uncommon. (C) 2009 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.

Dimensions of University Student Learning in Medicine and Pharmacy

Study orientations in higher education consist of various dimensions, such as approaches to learning, conceptions of learning and knowledge (i.e. epistemologies), self-regulation, and motivation. They have also been measured in different ways. The main orientations typically reported are reproducing and meaning orientations. The present study explored dimensions of study orientations, focusing in particular on pharmacy and medicine. New versions of self-report instruments were developed and tested in various contexts and in two countries. Furthermore, the linkages between study orientations and students epistemological development were explored. The context of problem-based (PBL) small groups was investigated in order to better understand how collaboration contributes to the quality of learning. The participants of Study I (n=66) were pharmacy students, who were followed during a three-year professionally oriented program in terms of their study orientations and epistemologies. A reproducing orientation to studying diminished during studying, whereas only a few students maintained their original level of meaning orientation. Dualism was found to be associated with a reproducing orientation. In Study II practices associated with deep and surface approaches to learning were measured in two differing ways, in order to better distinguish between what students believed to be useful in studying, and the extent to which they applied their beliefs to practice when preparing for examinations. Differences between domains were investigated by including a sample of Finnish and Swedish medical students (n=956) and a Finnish non-medical sample of university students (n=865). Memorizing and rote learning appeared as differing components of a surface approach to learning, while understanding, relating, and critical evaluation of knowledge emerged as aspects of a deep approach to learning. A structural model confirmed these results in both student samples. Study III explored a wide variety of dimensions of learning in medical education. Swedish medical students (n=280) answered the questionnaire. The deep approach to learning was strongly related to collaboration and reflective learning, whereas the surface approach was associated with novice-like views of knowledge and the valuing of certain and directly applicable knowledge. PBL students aimed at understanding, but also valued the role of memorization. Study IV investigated 12 PBL tutorial groups of students (n=116) studying microbiology and pharmacology in a medical school. The educational application was expected to support a deep approach to learning: Group members course grades in a final examination were related to the perceived functioning of the PBL tutorial groups. Further, the quality of cases that had been used as triggers for learning, was associated with the quality of small group functioning. New dimensions of study orientations were discovered. In particular, novel, finer distinctions were found within the deep approach component. In medicine, critical evaluation of knowledge appeared to be less valued than understanding and relating. Further, collaboration appeared to be closely related to the deep approach, and it was also important in terms of successful PBL studying. The results of the studies confirmed the previously found associations between approaches to learning and study success, but showed interesting context- and subgroup-related differences in this respect. Students ideas about the nature of knowledge and their approaches to learning were shown to be closely related. The present study expanded our understanding of the dimensions of study orientations, of their development, and their contextual variability in pharmacy and medicine.

Cyclin dependent protein kinases as drug targets – potential in cardiovascular diseases

Complications of atherosclerosis such as myocardial infarction and stroke are the primary cause of death in Western societies. The development of atherosclerotic lesions is a complex process, including endothelial cell dysfunction, inflammation, extracellular matrix alteration and vascular smooth muscle cell (VSMC) proliferation and migration. Various cell cycle regulatory proteins control VSMC proliferation. Protein kinases called cyclin dependent kinases (CDKs) play a major role in regulation of cell cycle progression. At specific phases of the cell cycle, CDKs pair with cyclins to become catalytically active and phosphorylate numerous substrates contributing to cell cycle progression. CDKs are also regulated by cyclin dependent kinase inhibitors, activating and inhibitory phosphorylation, proteolysis and transcription factors. This tight regulation of cell cycle is essential; thus its deregulation is connected to the development of cancer and other proliferative disorders such as atherosclerosis and restenosis as well as neurodegenerative diseases. Proteins of the cell cycle provide potential and attractive targets for drug development. Consequently, various low molecular weight CDK inhibitors have been identified and are in clinical development. Tylophorine is a phenanthroindolizidine alkaloid, which has been shown to inhibit the growth of several human cancer cell lines. It was used in Ayurvedic medicine to treat inflammatory disorders. The aim of this study was to investigate the effect of tylophorine on human umbilical vein smooth muscle cell (HUVSMC) proliferation, cell cycle progression and the expression of various cell cycle regulatory proteins in order to confirm the findings made with tylophorine in rat cells. We used several methods to determine our hypothesis, including cell proliferation assay, western blot and flow cytometric cell cycle distribution analysis. We demonstrated by cell proliferation assay that tylophorine inhibits HUVSMC proliferation dose-dependently with an IC50 value of 164 nM ± 50. Western blot analysis was used to determine the effect of tylophorine on expression of cell cycle regulatory proteins. Tylophorine downregulates cyclin D1 and p21 expression levels. The results of tylophorine’s effect on phosphorylation sites of p53 were not consistent. More sensitive methods are required in order to completely determine this effect. We used flow cytometric cell cycle analysis to investigate whether tylophorine interferes with cell cycle progression and arrests cells in a specific cell cycle phase. Tylophorine was shown to induce the accumulation of asynchronized HUVSMCs in S phase. Tylophorine has a significant effect on cell cycle, but its role as cell cycle regulator in treatment of vascular proliferative diseases and cancer requires more experiments in vitro and in vivo.

Antipyretic and antibacterial activity of Chloranthus erectus (Buch.-Ham.) Verdcourt leaf extract: A popular folk medicine of Arunachal Pradesh

Objective : The main objective of this work was to study the antipyretic and antibacterial activity of C. erectus (Buch.-Ham.) Verdcourt leaf extract in an experimental albino rat model. Materials and Methods : The methanol extract of C. erectus leaf (MECEL) was evaluated for its antipyretic potential on normal body temperature and Brewers yeast-induced pyrexia in albino rats model. While the antibacterial activity of MECEL against five Gram (-) and three Gram () bacterial strains and antimycotic activity was investigated against four fungi using agar disk diffusion and microdilution methods. Result : Yeast suspension (10 mL/kg b.w.) elevated rectal temperature after 19 h of subcutaneous injection. Oral administration of MECEL at 100 and 200 mg/kg b.w. showed significant reduction of normal rectal body temperature and yeast-provoked elevated temperature (38.8 0.2 and 37.6 0.4, respectively, at 2-3 h) in a dose-dependent manner, and the effect was comparable to that of the standard antipyretic drug-paracetamol (150 mg/kg b.w.). MECEL at 2 mg/disk showed broad spectrum of growth inhibition activity against both groups of bacteria. However, MECEL was not effective against the yeast strains tested in this study. Conclusion : This study revealed that the methanol extract of C. erectus exhibited significant antipyretic activity in the tested models and antibacterial activity as well, and may provide the scientific rationale for its popular use as antipyretic agent in Khamptiss folk medicines.

Oral malodour – background and diagnostics

Bad breath or oral malodour can be related to gingival diseases, trimethylaminuria, various inflammation diseases of upper respiratory tract, foreign bodies in nasal cavity etc. Bad breath is usually, in 85 % to 95 % of cases, inflicted by gram negative anaerobic bacteria in tongue coating. These bacteria have a tendency of producing foul-smelling sulphur containing gases called volatile sulphur compounds or VSC. Main cause of bad breath is parodontitis or postnasal drip into posterior part of the tongue. Detecting bad breath is most efficiently done by organoleptic method. By skilled analyser the reason for oral malodour can be determined with great accuracy. For scientific study the most effective method is gas chromatography (GC) with flame photometric detector (FPD). With it almost every component of exhaled air can be detected both quantitative and qualitative. Effective chairside methods include portable sulphur monitors and saliva tests.

Application of vibrational microspectroscopy to biology and medicine

Vibrational microspectroscopic (Raman and infrared (IR)) techniques are rapidly emerging as effective tools to probe the basic processes of life. This review mainly focuses on the applications of Raman and IR microspectroscopy to biology and biomedicine, ranging from studies on cellular components in single cells to advancement in techniques for in vitro to in vivo applications. These techniques have proved to be instrumental in studying the biological specimen with minimum perturbation, i.e. without the use of dyes and contrast-inducing agents. These techniques probe the vibrational modes of the molecules and provide spectra that are specific to the molecular properties and chemical nature of the species.

Hybrid molecules of carvacrol and benzoyl urea/thiourea with potential applications in agriculture and medicine

Benzoyl phenyl urea, a class of insect growth regulator's acts by inhibiting chitin synthesis. Carvacrol, a naturally occurring monoterpenoid is an effective antifungal agent. We have structurally modified carvacrol (2-methyl-5-1-methylethyl] phenol) by introducing benzoylphenyl urea linkage. Two series of benzoylcarvacryl thiourea (BCTU, 4a-f) and benzoylcarvacryl urea (BCU, 5a-f) derivatives were prepared and characterized by elemental analysis, IR, H-1 and C-13 NMR and Mass spectroscopy. Derivatives 4b, 4d, 4e, 4f and 5d, 5f showed comparable insecticidal activity with the standard BPU lufenuron against Dysdercus koenigii. BCTU derivatives 4c, 4e and BCU 5c showed good antifungal activity against phytopathogenic fungi viz. Magnaporthe grisae, Fusarium oxysporum, Dreschlera oryzae; food spoilage yeasts viz. Debaromyces hansenii, Pichia membranifaciens; and human pathogens viz. Candida albicans and Cryptococcus neoformans. Compounds 5d, 5e and 5f showed potent activity against human pathogens. Moderate and selective activity was observed for other compounds. All the synthesized compounds were non-haemolytic. These compounds have potential application in agriculture and medicine. (C) 2012 Elsevier Ltd. All rights reserved.