Brain and cognitive development

'The Millennial Adolescent' offers contemporary, stimulating insights for those currently teaching as well as those preparing to teach. This book investigates the characteristics of Generation Y, using students own voices, generational theory and case studies. The text is structured around the principle that effective teachers need to know who they are teaching as well as what to teach, how to teach it, and how to assess the outcome. Using generational theory, 'The Millennial Adolescent' investigates the characteristics of Generation Y, or the Millennial Generation, and points out what all teachers need to know about working with this current generation of students who are described in a number of ways digital natives, team oriented, confident, multi-taskers, high achievers, and a generation unlike any other. The book contains well-known frameworks for developing understandings about adolescents, blended and contrasted with a contemporary socio-cultural construction of adolescence, set in our particular time, era and society. This book reflects the uniqueness of Australian contexts, while connecting with international trends and global patterns. Engaging and full of insights, this book is essential reading for all professionals dealing with adolescents.

The stimulation of healing within a rat calvarial defect by mPCL–TCP/collagen scaffolds loaded with rhBMP-2

Bone morphogenetic proteins (BMPs) have been widely investigated for their clinical use in bone repair and it is known that a suitable carrier matrix to deliver them is essential for optimal bone regeneration within a specific defect site. Fused deposited modeling (FDM) allows for the fabrication of medical grade poly 3-caprolactone/tricalcium phosphate (mPCL–TCP) scaffolds with high reproducibility and tailor designed dimensions. Here we loaded FDM fabricated mPCL–TCP/collagen scaffolds with 5 mg recombinant human (rh)BMP-2 and evaluated bone healing within a rat calvarial critical-sized defect. Using a comprehensive approach, this study assessed the newly regenerated bone employing microcomputed tomography (mCT), histology/histomorphometry, and mechanical assessments. By 15 weeks, mPCL–TCP/collagen/rhBMP-2 defects exhibited complete healing of the calvarium whereas the non- BMP-2-loaded scaffolds showed significant less bone ingrowth, as confirmed by mCT. Histomorphometry revealed significantly increased bone healing amongst the rhBMP-2 groups compared to non-treated scaffolds at 4 and 15 weeks, although the % BV/TV did not indicate complete mineralisation of the entire defect site. Hence, our study confirms that it is important to combine microCt and histomorphometry to be able to study bone regeneration comprehensively in 3D. A significant up-regulation of the osteogenic proteins, type I collagen and osteocalcin, was evident at both time points in rhBMP-2 groups. Although mineral apposition rates at 15 weeks were statistically equivalent amongst treatment groups, microcompression and push-out strengths indicated superior bone quality at 15 weeks for defects treated with mPCL–TCP/collagen/rhBMP-2. Consistently over all modalities, the progression of healing was from empty defect < mPCL–TCP/collagen < mPCL–TCP/collagen/rhBMP-2, providing substantiating data to support the hypothesis that the release of rhBMP-2 from FDM-created mPCL–TCP/collagen scaffolds is a clinically relevant approach to repair and regenerate critically-sized craniofacial bone defects. Crown Copyright 2008 Published by Elsevier Ltd. All rights reserved.

Corneal confocal microscopy : a novel noninvasive means to diagnose neuropathy in patients with Fabry disease

ABSTRACT: Neuropathy is a cause of significant disability in patients with Fabry disease, yet its diagnosis is difficult. In this study we compared the novel noninvasive techniques of corneal confocal microscopy (CCM) to quantify small-fiber pathology, and non-contact corneal esthesiometry (NCCA) to quantify loss of corneal sensation, with established tests of neuropathy in patients with Fabry disease. Ten heterozygous females with Fabry disease not on enzyme replacement therapy (ERT), 6 heterozygous females, 6 hemizygous males on ERT, and 14 age-matched, healthy volunteers underwent detailed quantification of neuropathic symptoms, neurological deficits, neurophysiology, quantitative sensory testing (QST), NCCA, and CCM. All patients with Fabry disease had significant neuropathic symptoms and an elevated Mainz score. Peroneal nerve amplitude was reduced in all patients and vibration perception threshold was elevated in both male and female patients on ERT. Cold sensation (CS) threshold was significantly reduced in both male and female patients on ERT (P < 0.02), but warm sensation (WS)and heat-induced pain (HIP) were only significantly increased in males onERT (P<0.01). However, corneal sensation assessed withNCCAwas significantly reduced in female (P < 0.02) and male (P < 0.04) patients on ERT compared with control subjects. According to CCM, corneal nerve fiber and branch density was significantly reduced in female (P < 0.03) and male (P < 0.02) patients on ERT compared with control subjects. Furthermore, the severity of neuropathic symptoms and the neurological component of the Mainz Severity Score Index correlated significantly with QSTand CCM. This study shows that CCM and NCCA provide a novel means to detect early nerve fiber damage and dysfunction, respectively, in patients with Fabry disease.

Human brain regions required for the dividing and switching of attention between two features of a single object

This combined PET and ERP study was designed to identify the brain regions activated in switching and divided attention between different features of a single object using matched sensory stimuli and motor response. The ERP data have previously been reported in this journal [64]. We now present the corresponding PET data. We identified partially overlapping neural networks with paradigms requiring the switching or dividing of attention between the elements of complex visual stimuli. Regions of activation were found in the prefrontal and temporal cortices and cerebellum. Each task resulted in different prefrontal cortical regions of activation lending support to the functional subspecialisation of the prefrontal and temporal cortices being based on the cognitive operations required rather than the stimuli themselves.

A re-examination of the Ghrelin and Ghrelin receptor genes

The last few years have seen dramatic advances in genomics, including the discovery of a large number of non-coding and antisense transcripts. This has revolutionised our understanding of multifaceted transcript structures found within gene loci and their roles in the regulation of development, neurogenesis and other complex processes. The recent and continuing surge of knowledge has prompted researchers to reassess and further dissect gene loci. The ghrelin gene (GHRL) gives rise to preproghrelin, which in turn produces ghrelin, a 28 amino acid peptide hormone that acts via the ghrelin receptor (growth hormone secretagogue receptor/GHSR 1a). Ghrelin has many important physiological and pathophysiological roles, including the stimulation of growth hormone (GH) release, appetite regulation, and cancer development. A truncated receptor splice variant, GHSR 1b, does not bind ghrelin, but dimerises with GHSR 1a, and may act as a dominant negative receptor. The gene products of ghrelin and its receptor are frequently overexpressed in human cancer While it is well known that the ghrelin axis (ghrelin and its receptor) plays a range of important functional roles, little is known about the molecular structure and regulation of the ghrelin gene (GHRL) and ghrelin receptor gene (GHSR). This thesis reports the re-annotation of the ghrelin gene, discovery of alternative 5’ exons and transcription start sites, as well as the description of a number of novel splice variants, including isoforms with a putative signal peptide. We also describe the discovery and characterisation of a ghrelin antisense gene (GHRLOS), and the discovery and expression of a ghrelin receptor (growth hormone secretagogue receptor/GHSR) antisense gene (GHSR-OS). We have identified numerous ghrelin-derived transcripts, including variants with extended 5' untranslated regions and putative secreted obestatin and C-ghrelin transcripts. These transcripts initiate from novel first exons, exon -1, exon 0 and a 5' extended 1, with multiple transcription start sites. We used comparative genomics to identify, and RT-PCR to experimentally verify, that the proximal exon 0 and 5' extended exon 1 are transcribed in the mouse ghrelin gene, which suggests the mouse and human proximal first exon architecture is conserved. We have identified numerous novel antisense transcripts in the ghrelin locus. A candidate non-coding endogenous natural antisense gene (GHRLOS) was cloned and demonstrates very low expression levels in the stomach and high levels in the thymus, testis and brain - all major tissues of non-coding RNA expression. Next, we examined if transcription occurs in the antisense orientation to the ghrelin receptor gene, GHSR. A novel gene (GHSR-OS) on the opposite strand of intron 1 of the GHSR gene was identified and characterised using strand-specific RT-PCR and rapid amplification of cDNA ends (RACE). GHSR-OS is differentially expressed and a candidate non-coding RNA gene. In summary, this study has characterised the ghrelin and ghrelin receptor loci and demonstrated natural antisense transcripts to ghrelin and its receptor. Our preliminary work shows that the ghrelin axis generates a broad and complex transcriptional repertoire. This study provides the basis for detailed functional studies of the the ghrelin and GHSR loci and future studies will be needed to further unravel the function, diagnostic and therapeutic potential of the ghrelin axis.

Brain-derived neurotrophic factor (BDNF) gene : no major impact on antidepressant treatment response

The brain-derived neurotrophic factor (BDNF) has been suggested to play a pivotal role in the aetiology of affective disorders. In order to further clarify the impact of BDNF gene variation on major depression as well as antidepressant treatment response, association of three BDNF polymorphisms [rs7103411, Val66Met (rs6265) and rs7124442] with major depression and antidepressant treatment response was investigated in an overall sample of 268 German patients with major depression and 424 healthy controls. False discovery rate (FDR) was applied to control for multiple testing. Additionally, ten markers in BDNF were tested for association with citalopram outcome in the STAR*D sample. While BDNF was not associated with major depression as a categorical diagnosis, the BDNF rs7124442 TT genotype was significantly related to worse treatment outcome over 6 wk in major depression (p=0.01) particularly in anxious depression (p=0.003) in the German sample. However, BDNF rs7103411 and rs6265 similarly predicted worse treatment response over 6 wk in clinical subtypes of depression such as melancholic depression only (rs7103411: TT

Controversies of prophylactic hypothermia and the emerging use of brain tissue oxygen tension monitoring and decompressive craniectomy in traumatic brain-injured children

Background Despite being the leading cause of death and disability in the paediatric population, traumatic brain injury (TBI) in this group is largely understudied. Clinical practice within the paediatric intensive care unit (PICU) has been based upon adult guidelines however children are significantly different in terms of mechanism, pathophysiology and consequence of injury. Aim To review TBI management in the PICU and gain insight into potential management strategies. Method To conduct this review, a literature search was conducted using MEDLINE, PUBMED and The Cochrane Library using the following key words; traumatic brain injury; paediatric; hypothermia. There were no date restrictions applied to ensure that past studies, whose principles remain current were not excluded. Results Three areas were identified from the literature search and will be discussed against current acknowledged treatment strategies: Prophylactic hypothermia, brain tissue oxygen tension monitoring and decompressive craniectomy. Conclusion Previous literature has failed to fully address paediatric specific management protocols and we therefore have little evidence-based guidance. This review has shown that there is an emerging and ongoing trend towards paediatric specific TBI research in particular the area of moderate prophylactic hypothermia (MPH).

RatSLAM on the edge : revealing a coherent representation from an overloaded rat brain

The RatSLAM system can perform vision based SLAM using a computational model of the rodent hippocampus. When the number of pose cells used to represent space in RatSLAM is reduced, artifacts are introduced that hinder its use for goal directed navigation. This paper describes a new component for the RatSLAM system called an experience map, which provides a coherent representation for goal directed navigation. Results are presented for two sets of real world experiments, including comparison with the original goal memory system's performance in the same environment. Preliminary results are also presented demonstrating the ability of the experience map to adapt to simple short term changes in the environment.

Do clients with acquired brain injury use the splints prescribed by occupational therapists? A descriptive study

Clients with acquired brain injury often demonstrate hypertonicity and decreased function in their upper limbs, requiring appropriate intervention. Splinting is one of the intervention methods that is widely used to address these issues. Literature shows that some clients are not using splints following fabrication. However, there is a paucity of research about the factors that influence clients to use or not use splints. This study aims to investigate these influential factors for clients with upper limb hypertonicity. Two survey tools including therapist and client questionnaires were developed and completed by both therapists and clients. Six therapists and 14 clients participated in this study and completed the relevant questionnaires. The results illustrate that most clients (13 out of 14) were continuing to use their splints four weeks following discharge from hospital. The main goals of choosing splints for both therapists and clients were prevention of contracture and deformity. The most indicated client reasons for adhering to the splint wearing program were therapist-related factors including clients’ trust and reliance on their therapists. Further reasons for clients implementing the recommended splint-wearing program and clinical implications are discussed.

The expression of ADAM-9 and -10 in prostate cancer and their regulation by dihydrotestosterone, insulin-like growth Factor-1 and epidermal growth factor

Prostrate Cancer(PCa)is the most common cause of cancer death amongst Western males. PCa occurs in two distinct stages. In its early stage, growth and development is dependent primarily on male sex hormones (androgens) such as testosterone, although other growth factors have roles maintaining PCa cell survival in this stage. In the later stage of PCa development, growth and.maintenance is independent of androgen stimulation and growth factors including Insulin-like Growth Factor -1 (IGf.:·l) and Epidermal Growth Factor (EGF) are thought to have more crucial roles in cell survival and PCa progression. PCa, in its late stages, is highly aggressive and metastatic, that is, tumorigenic cells migrate from the primary site of the body (prostate) and travel via the systemic and lymphatic circulation, residing and colonising in the bone, lymph node, lung, and in more rare cases, the brain. Metastasis involves both cell migration and tissue degradation activities. The degradation of the extracellular matrix (ECM), the tissue surrounding the organ, is mediated in part by members of a family of 26 proteins called the Matrix Metalloproteases (MMPs), whilst ceil adhesion molecules, of which proteins known as Integrins are included, mediate ce11 migration. A family of proteins known as the ADAMs (A Disintegrin . And Metalloprotease domain) were a recently characterised family at the commencement of this study and now comprise 34 members. Because of their dual nature, possessing an active metaiioprotease domain, homologous to that of the MMPs, and an integrin-binding domain capable of regulating cell-cell and cell-ECM contacts, it was thought likely that members of the ADAMs family may have implications for the progression of aggressive cancers such as those ofthe prostate. This study focussed on two particular ADAMs -9 and -10. ADAM-9 has an active metalloprotease domain, which has been shown to degrade constituents of the ECM, including fibronectin, in vitro. It also has an integrin-binding capacity through association with key integrins involved in PCa progression, such as a6~1. ADAM-10 has no such integrin binding activities, but its bovine orthologue, MADM, is able to degrade coHagen type IV, a major component of basement membranes. It is likely human ADAM-10 has the same activity. It is also known to cleave Ll -a protein involved in cell anchorage activities - and collagen type XVII - which is a principal component of the hemidesmosomes of cellular tight junctions. The cleavage of these proteins enables the cell to be released from the surrounding environment and commence migratory activities, as required in metastasis. Previous studies in this laboratory showed the mRNA expression of the five ADAMs -9,- 10, -11, -15 and -17 in PCa cell lines, characteristic of androgen-dependent and androgen independent disease. These studies were furthered by the characterisation of AD AM-9, -10 and -17 mRNA regulation by Dihydrotestosterone (DHT) in the androgen-responsive cell line (LNCaP). ADAM-9 and -10 mRNA levels were elevated in response to DHT stimulation. Further to these observations, the expression of ADAM-9 and -10 was shown in primary prostate biopsies from patients with PCa. ADAM-1 0 was expressed in the cytoplasm and on the ceH membrane in epithelial and basal cells ofbenign prostate glands, but in high-grade PCa glands, ADAM-I 0 expression was localised to the nucleus and its expression levels appeared to be elevated when compared to low-grade PCa glands. These studies provided a strong background for the hypothesis that ADAM-9 and -10 have key roles in the development ofPCa and provided a basis for further studies.The aims of this study were to: 1) characterise the expression, localisation and levels, of ADAM-9 and -10 mRNA and protein in cell models representing characteristics of normal through androgen-dependent to androgen-independent PCa, as well as to expand the primary PCa biopsy data for ADAM-9 and ADAM-10 to encompass PCa bone metastases 2) establish an in vitro cell system, which could express elevated levels of ADAM-1 0 so that functional cell-based assays such as cell migration, invasion and attachment could be carried out, and 3) to extend the previous hormonal regulation data, to fully characterise the response of ADAM-9 and -10 mRNA and protein levels to DHT, IGF-1, DHT plus IGF-1 and EGF in the hormonal/growth factor responsive cell line LNCaP. For aim 1 (expression of ADAM-9 and -10 mRNA and protein), ADAM-9 and -10 mRNA were characterised by R T -PCR, while their protein products were analysed by Western blot. Both ADAM-9 and -10 mRNA and protein were expressed at readily detectable levels across progressively metastatic PCa cell lines model that represent characteristics of low-grade,. androgen-dependent (LNCaP and C4) to high-grade, androgen-independent (C4-2 and C4-2B) PCa. When the non-tumorigenic prostate cell line RWPE-1 was compared with the metastatic PCa cell line PC-3, differential expression patterns were seen by Western blot analysis. For ADAM-9, the active form was expressed at higher levels in RWPE-1, whilst subcellular fractionation showed that the active form of ADAM-9 was predominantly located in the cell nucleus. For ADAM-I 0, in both of the cell Jines, a nuclear specific isoform of the mature, catalytically active ADAM-I 0 was found. This isoforrn differed by -2 kDa in Mr (smaller) than the cytoplasmic specific isoform. Unprocessed ADAM-I 0 was readily detected in R WPE-1 cell lines but only occasionally detected in PC-3 cell lines. Immunocytochemistry using ADAM-9 and -10 specific antibodies confirmed nuclear, cytoplasmic and membrane expression of both ADAMs in these two cell lines. To examine the possibility of ADAM-9 and -10 being shed into the extracellular environment, membrane vesicles that are constitutively shed from the cell surface and contain membrane-associated proteins were collected from the media of the prostate cell lines RWPE-1, LNCaP and PC-3. ADAM-9 was readily detectable in RWPE- 1 and LNCaP cell membrane vesicles by Western blot analysis, but not in PC-3 cells, whilst the expression of ADAM-I 0 was detected in shed vesicles from each of these prostate cell lines. By Laser Capture Microdissection (LCM), secretory epithelial cells of primary prostate gland biopsies were isolated from benign and malignant glands. These secretory cells, by Western blot analysis, expressed similar Mr bands for ADAM-9 and -10 that were found in PCa cell lines in vitro, indicating that the nuclear specific isoforrn of ADAM-I 0 was present in PCa primary tumours and may represent the predominantly nuclear form of ADAM-I 0 expression, previously shown in high-grade PCa by immunohistochemistry (IHC). ADAM-9 and -10 were also examined by IHC in bone metastases taken from PCa patients at biopsy. Both ADAMs could be detected at levels similar to those shown for Prostate Specific Antigen (PSA) in these biopsies. Furthermore, both ADAM-9 and -10 were predominantly membrane- bound with occasional nuclear expression. For aim 2, to establish a cell system that over-expressed levels of ADAM-10, two fulllength ADAM-I 0 mammalian expression vectors were constructed; ADAM-I 0 was cloned into pcDNA3.1, which contains a CMV promoter, and into pMEP4, containing an inducible metallothionine promoter, whose activity is stimulated by the addition of CdC}z. The efficiency of these two constructs was tested by way of transient transfection in the PCa cell line PC-3, whilst the pcDNA3.1 construct was also tested in the RWPE-1 prostate cell line. Resultant Western blot analysis for all transient transfection assays showed that levels of ADAM-I 0 were not significantly elevated in any case, when compared to levels of the housekeeping gene ~-Tubulin, despite testing various levels of vector DNA, and, for pMEP4, the induction of the transfected cell system with different degrees of stimulation with CdCh to activate the metallothionine promoter post-transfection. Another study in this laboratory found similar results when the same full length ADAM-10 sequence was cloned into a Green Fluorescent Protein (GFP) expressing vector, as no fluorescence was observed by means of transient tran sfection in the same, and other, PCa cell lines. It was hypothesised that the Kozak sequence included in the full-length construct (human ADAMI 0 naturally occurring sequence) is not strong enough to initiate translation in an artificial system, in cells, which, as described in Aim 1, are already expressing readily detectable levels of endogenous ADAM-10. As a result, time constraints prevented any further progress with Aim 2 and functional studies including cell attachment, invasion and migration were unable to be explored. For Aim 3, to characterise the response of ADAM-9 and -10 mRNA and protein levels to DHT, IGF-1, DHT plus IGF-1 and EGF in LNCaP cells, the levels of ADAM-9 and -10 mRNA were not stimulated by DHT or IGF-I alone, despite our previous observations that initially characterised ADAM-9 and -10 mRNA as being responsive to DHT. However, IGF-1 in synergy with DHT did significantly elevate mRNA levels ofboth ADAMs. In the case of ADAM-9 and -10 protein, the same trends of stimulation as found at the rnRNA level were shown by Western blot analysis when ADAM-9 and -10 signal intensity was normalised with the housekeeping protein ~-Tubulin. For EGF treatment, both ADAM-9 and -10 mRNA and protein levels were significantly elevated, and further investigation vm found this to be the case for each of these ADAMs proteins in the nuclear fractions of LNCaP cells. These studies are the first to describe extensively, the expression and hormonal/growth factor regulation of two members of the ADAMs family ( -9 and -1 0) in PCa. These observations imply that the expression of ADAM-9 and -10 have varied roles in PCa whilst it develops from androgen-sensitive (early stage disease), through to an androgeninsensitive (late-stage), metastatic disease. Further studies are now required to investigate the several key areas of focus that this research has revealed, including: • Investigation of the cellular mechanisms that are involved in actively transporting the ADAMs to the cell's nuclear compartment and the ADAMs functional roles in the cell nucleus. • The construction of a full-length human ADAM-10 mammalian expression construct with the introduction of a new Kozak sequence, that elevates ADAM-I 0 expression in an in vitro cell system are required, so that functional assays such as cell invasion, migration and attachment may be carried out to fmd the functional consequences of ADAM expression on cellular behaviour. • The regulation studies also need to be extended by confirming the preliminary observations that the nuclear levels of ADAMs may also be elevated by hormones and growth factors such as DHT, IGF-1 and EGF, as well as the regulation of levels of plasma membrany vesicle associated ADAM expression. Given the data presented in this study, it is likely the ADAMs have differential roles throughout the development of PCa due to their differential cellular localisation and synergistic growth-factor regulation. These observations, along with those further studies outlined above, are necessary in identifying these specific components ofPCa metastasis to which the ADAMs may contribute.

Lateral shearing interferometry, dynamic wavefront sensing, and high-speed videokeratoscopy for noninvasive assessment of tear film surface characteristics : a comparitive study

There are several noninvasive techniques for assessing the kinetics of tear film, but no comparative studies have been conducted to evaluate their efficacies. Our aim is to test and compare techniques based on high-speed videokeratoscopy (HSV), dynamic wavefront sensing (DWS), and lateral shearing interferometry (LSI). Algorithms are developed to estimate the tear film build-up time TBLD, and the average tear film surface quality in the stable phase of the interblink interval TFSQAv. Moderate but significant correlations are found between TBLD measured with LSI and DWS based on vertical coma (Pearson's r2=0.34, p<0.01) and higher order rms (r2=0.31, p<0.01), as well as between TFSQAv measured with LSI and HSV (r2=0.35, p<0.01), and between LSI and DWS based on the rms fit error (r2=0.40, p<0.01). No significant correlation is found between HSV and DWS. All three techniques estimate tear film build-up time to be below 2.5 sec, and they achieve a remarkably close median value of 0.7 sec. HSV appears to be the most precise method for measuring tear film surface quality. LSI appears to be the most sensitive method for analyzing tear film build-up.

Corneal confocal microscopy : a novel noninvasive test to diagnose and stratify the severity of human diabetic neuropathy

OBJECTIVE: The accurate quantification of human diabetic neuropathy is important to define at-risk patients, anticipate deterioration, and assess new therapies. ---------- RESEARCH DESIGN AND METHODS: A total of 101 diabetic patients and 17 age-matched control subjects underwent neurological evaluation, neurophysiology tests, quantitative sensory testing, and evaluation of corneal sensation and corneal nerve morphology using corneal confocal microscopy (CCM). ---------- RESULTS: Corneal sensation decreased significantly (P = 0.0001) with increasing neuropathic severity and correlated with the neuropathy disability score (NDS) (r = 0.441, P < 0.0001). Corneal nerve fiber density (NFD) (P < 0.0001), nerve fiber length (NFL), (P < 0.0001), and nerve branch density (NBD) (P < 0.0001) decreased significantly with increasing neuropathic severity and correlated with NDS (NFD r = −0.475, P < 0.0001; NBD r = −0.511, P < 0.0001; and NFL r = −0.581, P < 0.0001). NBD and NFL demonstrated a significant and progressive reduction with worsening heat pain thresholds (P = 0.01). Receiver operating characteristic curve analysis for the diagnosis of neuropathy (NDS >3) defined an NFD of <27.8/mm2 with a sensitivity of 0.82 (95% CI 0.68–0.92) and specificity of 0.52 (0.40–0.64) and for detecting patients at risk of foot ulceration (NDS >6) defined a NFD cutoff of <20.8/mm2 with a sensitivity of 0.71 (0.42–0.92) and specificity of 0.64 (0.54–0.74). ---------- CONCLUSIONS: CCM is a noninvasive clinical technique that may be used to detect early nerve damage and stratify diabetic patients with increasing neuropathic severity. Established diabetic neuropathy leads to pain and foot ulceration. Detecting neuropathy early may allow intervention with treatments to slow or reverse this condition (1). Recent studies suggested that small unmyelinated C-fibers are damaged early in diabetic neuropathy (2–4) but can only be detected using invasive procedures such as sural nerve biopsy (4,5) or skin-punch biopsy (6–8). Our studies have shown that corneal confocal microscopy (CCM) can identify early small nerve fiber damage and accurately quantify the severity of diabetic neuropathy (9–11). We have also shown that CCM relates to intraepidermal nerve fiber loss (12) and a reduction in corneal sensitivity (13) and detects early nerve fiber regeneration after pancreas transplantation (14). Recently we have also shown that CCM detects nerve fiber damage in patients with Fabry disease (15) and idiopathic small fiber neuropathy (16) when results of electrophysiology tests and quantitative sensory testing (QST) are normal. In this study we assessed corneal sensitivity and corneal nerve morphology using CCM in diabetic patients stratified for the severity of diabetic neuropathy using neurological evaluation, electrophysiology tests, and QST. This enabled us to compare CCM and corneal esthesiometry with established tests of diabetic neuropathy and define their sensitivity and specificity to detect diabetic patients with early neuropathy and those at risk of foot ulceration.

Factors influencing quality of life in patients with benign primary brain tumors : prior to and following surgery

Goals: Few studies have repeatedly evaluated quality of life and potentially relevant factors in patients with benign primary brain tumor. The purpose of this study was to explore the relationship between the experience of the symptom distress, functional status, depression, and quality of life prior to surgery (T1) and 1 month post-discharge (T2). ---------- Patients and methods: This was a prospective cohort study including 58 patients with benign primary brain tumor in one teaching hospital in the Taipei area of Taiwan. The research instruments included the M.D. Anderson Symptom Inventory, the Functional Independence Measure scale, the Hospital Depression Scale, and the Functional Assessment of Cancer Therapy-Brain.---------- Results: Symptom distress (T1: r=−0.90, p<0.01; T2: r=−0.52, p<0.01), functional status (T1: r=0.56, p<0.01), and depression (T1: r=−0.71, p<0.01) demonstrated a significant relationship with patients' quality of life. Multivariate analysis identified symptom distress (explained 80.2%, Rinc 2=0.802, p=0.001) and depression (explained 5.2%, Rinc 2=0.052, p<0.001) continued to have a significant independent influence on quality of life prior to surgery (T1) after controlling for key demographic and medical variables. Furthermore, only symptom distress (explained 27.1%, Rinc 2=0.271, p=0.001) continued to have a significant independent influence on quality of life at 1 month after discharge (T2).---------- Conclusions: The study highlights the potential importance of a patient's symptom distress on quality of life prior to and following surgery. Health professionals should inquire about symptom distress over time. Specific interventions for symptoms may improve the symptom impact on quality of life. Additional studies should evaluate symptom distress on longer-term quality of life of patients with benign brain tumor.

Making sense of brain tumour: A qualitative investigation of personal and social processes of adjustment

This study investigated personal and social processes of adjustment at different stages of illness for individuals with brain tumour. A purposive sample of 18 participants with mixed tumour types (9 benign and 9 malignant) and 15 family caregivers was recruited from a neurosurgical practice and a brain tumour support service. In-depth semi-structured interviews focused on participants’ perceptions of their adjustment, including personal appraisals, coping and social support since their brain tumour diagnosis. Interview transcripts were analysed thematically using open, axial and selective coding techniques. The primary theme that emerged from the analysis entailed “key sense making appraisals”, which was closely related to the following secondary themes: (1) Interactions with those in the healthcare system, (2) reactions and support from the personal support network, and (3) a diversity of coping efforts. Adjustment to brain tumour involved a series of appraisals about the illness that were influenced by interactions with those in the healthcare system, reactions and support from people in their support network, and personal coping efforts. Overall, the findings indicate that adjustment to brain tumour is highly individualistic; however, some common personal and social processes are evident in how people make sense of and adapt to the illness over time. A preliminary framework of adjustment based on the present findings and its clinical relevance are discussed. In particular, it is important for health professionals to seek to understand and support individuals’ sense-making processes following diagnosis of brain tumour.