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.

Cell interactions of osteoarthritic subchondral bone osteoblasts and articular chondrocytes aggravate MMP-2 and MMP-9 production through the mediation of ERK1/2 and JNK phosphorylation

Matrix Metalloproteinases (MMP) play a key role in osteoarthritis (OA) development. The aim of the present study was to investigate whether, the cross-talk between subchondral bone osteoblasts (SBOs) and articular cartilage chondrocytes (ACCs) in OA alters the expression and regulation of MMPs, and also to test the potential involvement of mitogen activated protein kinase (MAPK) signalling pathway during this process.

Evaluation of the Scottsdale Loop 101 automated speed enforcement demonstration program

Speeding is recognized as a major contributing factor in traffic crashes. In order to reduce speed-related crashes, the city of Scottsdale, Arizona implemented the first fixed-camera photo speed enforcement program (SEP) on a limited access freeway in the US. The 9-month demonstration program spanning from January 2006 to October 2006 was implemented on a 6.5 mile urban freeway segment of Arizona State Route 101 running through Scottsdale. This paper presents the results of a comprehensive analysis of the impact of the SEP on speeding behavior, crashes, and the economic impact of crashes. The impact on speeding behavior was estimated using generalized least square estimation, in which the observed speeds and the speeding frequencies during the program period were compared to those during other periods. The impact of the SEP on crashes was estimated using 3 evaluation methods: a before-and-after (BA) analysis using a comparison group, a BA analysis with traffic flow correction, and an empirical Bayes BA analysis with time-variant safety. The analysis results reveal that speeding detection frequencies (speeds> or =76 mph) increased by a factor of 10.5 after the SEP was (temporarily) terminated. Average speeds in the enforcement zone were reduced by about 9 mph when the SEP was implemented, after accounting for the influence of traffic flow. All crash types were reduced except rear-end crashes, although the estimated magnitude of impact varies across estimation methods (and their corresponding assumptions). When considering Arizona-specific crash related injury costs, the SEP is estimated to yield about $17 million in annual safety benefits.

Infant and young child feeding indicators and determinants of poor feeding practices in India : secondary data analysis of National Family Health Survey 2005–06

Background: In India, poor feeding practices in early childhood contribute to the burden of malnutrition and infant and child mortality. Objective. To estimate infant and young child feeding indicators and determinants of selected feeding practices in India. Methods: The sample consisted of 20,108 children aged 0 to 23 months from the National Family Health Survey India 2005–06. Selected indicators were examined against a set of variables using univariate and multivariate analyses. Results: Only 23.5% of mothers initiated breastfeeding within the first hour after birth, 99.2% had ever breastfed their infant, 89.8% were currently breastfeeding, and 14.8% were currently bottle-feeding. Among infants under 6 months of age, 46.4% were exclusively breastfed, and 56.7% of those aged 6 to 9 months received complementary foods. The risk factors for not exclusively breastfeeding were higher household wealth index quintiles (OR for richest = 2.03), delivery in a health facility (OR = 1.35), and living in the Northern region. Higher numbers of antenatal care visits were associated with increased rates of exclusive breastfeeding (OR for ≥ 7 antenatal visits = 0.58). The rates of timely initiation of breastfeeding were higher among women who were better educated (OR for secondary education or above = 0.79), were working (OR = 0.79), made more antenatal clinic visits (OR for ≥ 7 antenatal visits = 0.48), and were exposed to the radio (OR = 0.76). The rates were lower in women who were delivered by cesarean section (OR = 2.52). The risk factors for bottle-feeding included cesarean delivery (OR = 1.44), higher household wealth index quintiles (OR = 3.06), working by the mother (OR=1.29), higher maternal education level (OR=1.32), urban residence (OR=1.46), and absence of postnatal examination (OR=1.24). The rates of timely complementary feeding were higher for mothers who had more antenatal visits (OR=0.57), and for those who watched television (OR=0.75). Conclusions: Revitalization of the Baby Friendly Hospital Initiative in health facilities is recommended. Targeted interventions may be necessary to improve infant feeding practices in mothers who reside in urban areas, are more educated, and are from wealthier households.

Proceedings of the 21st Australian Software Engineering Conference (ASWEC 2010) : 6-9 April 2010, Auckland, New Zealand.

ASWEC is a joint conference of Engineers Australia and the Australian Computer Society reporting through the Engineers Australia/ACS Joint Board on Software Engineering.

Health risk from the use of roof-harvested rainwater in Southeast Queensland, Australia, as potable or nonpotable water, determined using quantitative microbial risk assessment

A total of 214 rainwater samples from 82 tanks were collected in urban Southeast Queensland (SEQ) in Australia and analysed for the zoonotic bacterial and protozoan pathogen using real-time binary PCR and quantitative PCR (qPCR). Quantitative Microbial Risk Assessment (QMRA) analysis was used to quantify the risk of infection associated with the exposure to potential pathogens from potable and non-potable uses of roof-harvested rainwater. Of the 214 samples tested, 10.7%, 9.8%, and 5.6%, and 0.4% samples were positive for Salmonella invA, Giardia lamblia β-giardin , Legionella pneumophila mip, and Campylobacter jejuni mapA genes. Cryptosporidium parvum could not be detected. The estimated numbers of viable Salmonella spp., G. lamblia β-giradin, and L. pneumophila genes ranged from 1.6 × 101 to 9.5 × 101 cells, 1.4 × 10-1 to 9.0 × 10-1 cysts, and 1.5 × 101 to 4.3 × 101 per 1000 ml of water, respectively. Six risk scenarios were considered from exposure to Salmonella spp., G. lamblia and L. pneumophila. For Salmonella spp., and G. lamblia, these scenarios were: (1) liquid ingestion due to drinking of rainwater on a daily basis (2) accidental liquid ingestion due to garden hosing twice a week (3) aerosol ingestion due to showering on a daily basis, and (4) aerosol ingestion due to hosing twice a week. For L. pneumophila, these scenarios were: (5) aerosol inhalation due to showering on a daily basis, and (6) aerosol inhalation due to hosing twice a week. The risk of infection from Salmonella spp., G. lamblia, and L. pneumophila associated with the use of rainwater for showering and garden hosing was calculated to be well below the threshold value of one extra infection per 10,000 persons per year in urban SEQ. However, the risk of infection from ingesting Salmonella spp. and G. lamblia via drinking exceeds this threshold value, and indicates that if undisinfected rainwater were ingested by drinking, then the gastrointestinal diseases of Salmonellosis and Giardiasis is expected to range from 5.0 × 100 to 2.8 × 101 (Salmonellosis) and 1.0 × 101 to 6.4 × 101 (Giardiasis) cases per 10,000 persons per year, respectively. Since this health risk seems higher than that expected from the reported incidences of gastroenteritis, the assumptions used to estimate these infection risks are critically examined. Nonetheless, it would seem prudent to disinfect rainwater for potable use.

Which components of heart failure programs are effective? A meta-analysis of the outcomes of structured telephone support or telemonitoring as the primary component of heart failure management in 9,560 patients (Abridged Cochrane Review)

Aims--Telemonitoring (TM) and structured telephone support (STS) have the potential to deliver specialised management to more patients with chronic heart failure (CHF), but their efficacy is still to be proven. Objectives To review randomised controlled trials (RCTs) of TM or STS on all- cause mortality and all-cause and CHF-related hospitalisations in patients with CHF, as a non-invasive remote model of specialised disease-management intervention.--Methods and Results--Data sources:We searched 15 electronic databases and hand-searched bibliographies of relevant studies, systematic reviews, and meeting abstracts. Two reviewers independently extracted all data. Study eligibility and participants: We included any randomised controlled trials (RCT) comparing TM or STS to usual care of patients with CHF. Studies that included intensified management with additional home or clinic visits were excluded. Synthesis: Primary outcomes (mortality and hospitalisations) were analysed; secondary outcomes (cost, length of stay, quality of life) were tabulated.--Results: Thirty RCTs of STS and TM were identified (25 peer-reviewed publications (n=8,323) and five abstracts (n=1,482)). Of the 25 peer-reviewed studies, 11 evaluated TM (2,710 participants), 16 evaluated STS (5,613 participants) and two tested both interventions. TM reduced all-cause mortality (risk ratio (RR 0•66 [95% CI 0•54-0•81], p<0•0001) and STS showed similar trends (RR 0•88 [95% CI 0•76-1•01], p=0•08). Both TM (RR 0•79 [95% CI 0•67-0•94], p=0•008) and STS (RR 0•77 [95% CI 0•68-0•87], p<0•0001) reduced CHF-related hospitalisations. Both interventions improved quality of life, reduced costs, and were acceptable to patients. Improvements in prescribing, patient-knowledge and self-care, and functional class were observed.--Conclusion: TM and STS both appear effective interventions to improve outcomes in patients with CHF.

Identification of novel markers for uncomplicated lower genital tract infections and upper genital tract pathology due to Chlamydia trachomatis.

Background: Untreated Chlamydia trachomatis infections in women can result in disease sequelae such as salpingitis and pelvic inflammatory disease (PID), ultimately culminating in tubal occlusion and infertility. Whilst nucleic acid amplification tests can effectively diagnose uncomplicated lower genital tract (LGT) infections, they are not suitable for diagnosing upper genital tract (UGT) pathological sequelae. As a consequence, this study aimed to identify serological markers that can, with a high degree of sensitivity and specificity, discriminate between LGT infections and UGT pathology. Methods: Plasma was collected from 73 women with a history of LGT infection, UGT pathology due to C. trachomatis or no serological evidence of C. trachomatis infection. Western blotting was used to analyse antibody reactivity against extracted chlamydial proteins. Sensitivity and specificity of differential markers were also calculated. Results: Four antigens (CT157, CT423, CT727 and CT396) were identified and found to be capable of discriminating between the infection and disease sequelae state. Sensitivity and specificity calculations showed that our assay for diagnosing LGT infection had a sensitivity and specificity of 75% and 76% respectively, whilst the assay for identifying UGT pathology demonstrated 80% sensitivity and 86% specificity. Conclusions: The use of these assays could potentially facilitate earlier diagnoses in women suffering UGT pathology due to C. trachomatis.

Maternal administration of erythromycin fails to eradicate intrauterine ureaplasma infection in an ovine model

Erythromycin is the standard antibiotic used for treatment of Ureaplasma species during 3 pregnancy; however, maternally administered erythromycin may be ineffective at eliminating 4 intra-amniotic ureaplasma infections. We asked if erythromycin would eradicate intra-amniotic 5 ureaplasma infections in pregnant sheep. At 50 days of gestation (d, term=150d) pregnant ewes 6 received intra-amniotic injections of erythromycin-sensitive U. parvum serovar 3 (n=16) or 10B 7 medium (n=16). At 100d, amniocentesis was performed; five fetal losses (ureaplasma group: 8 n=4; 10B group: n=1) had occurred by this time. Remaining ewes were allocated into treatment 9 subgroups: medium only (M, n=7); medium and erythromycin (M/E, n=8); ureaplasma only (Up, 10 n=6) or ureaplasma and erythromycin (Up/E, n=6). Erythromycin was administered intra11 muscularly (500 mg), eight-hourly for four days (100d-104d). Amniotic fluid samples were 12 collected at 105d. At 125d preterm fetuses were surgically delivered and specimens were 13 collected for culture and histology. Erythromycin was quantified in amniotic fluid by liquid 14 chromatography-mass spectrometry. Ureaplasmas were isolated from the amniotic fluid, 15 chorioamnion and fetal lung of animals from the Up and Up/E groups, however, the numbers of 16 U. parvum recovered were not different between these groups. Inflammation in the 17 chorioamnion, cord and fetal lung was increased in ureaplasma-exposed animals compared to 18 controls, but was not different between the Up and Up/E groups. Erythromycin was detected in 19 amniotic fluid samples, although concentrations were low (<10-76 ng/mL). This study 20 demonstrates that maternally administered erythromycin does not eradicate chronic, intra- amniotic ureaplasma infections or improve fetal outcomes in an ovine model, potentially due to 22 the poor placental passage of erythromycin.

Cracking the language code : NAPLAN numeracy tests in years 7 and 9

Focusing on the use of language is a crucial strategy in good mathematics teaching and a teacher’s guidance can assist students to master the language of mathematics. This article discusses the statements with reference to recent year 7 and 9 NAPLAN numeracy tests. It draws the readers’ attention to the complexities of language in the field of mathematics. Although this article refers to NAPLAN numeracy tests it also offers advice about good teaching practice.

Self-defence against terrorism in the post 9/11 world

In 1986 the then United States Secretary of State George Shultz asserted that: It is absurd to argue that international law prohibits us from capturing terrorists in international waters or airspace; from attacking them on the soil of other nations, even for the purpose of rescuing hostages; or from using force against states that support, train and harbor terrorists or guerrillas. At that time the United States’ claim of a right to use military force in self-defence against terrorism2 received little support from other states.3 The predominant view then was that terrorist attacks committed by private or non-state actors were a form of criminal activity to be combated through domestic and international criminal justice mechanisms. The notion that such terrorist acts should be treated as ‘armed attacks’ triggering a victim state’s right of self-defence was not accepted by the majority of states. To suggest, as Shultz had done, that a state not directly responsible for terrorist acts could have its territorial integrity violated by military action targeting terrorists located within that state, was a controversial proposition in 1986. However, some fifteen years later, when the United States and a coalition of allies launched a military campaign in Afghanistan following the 11 September 2001 (hereafter ‘9/11’) terrorist attacks, there was virtually unanimous international support for the use of force.

The spermostatic and microbicidal actions of quinones and malemides : towards a dual-purpose contraceptive agent

There is an urgent need to develop safe, effective, dual-purpose contraceptive agents that combine the prevention of pregnancy with protection against sexually transmitted diseases. Here we report the identification of a group of compounds that on contact with human spermatozoa induce a state of “spermostasis,” characterized by the extremely rapid inhibition of sperm movement without compromising cell viability. These spermostatic agents were more active and significantly less toxic than the reagent in current clinical use, nonoxynol 9, giving therapeutic indices (ratio of spermostatic to cytotoxic activity) that were orders of magnitude greater than this traditional spermicide. Although certain compounds could trigger reactive oxygen species generation by spermatozoa, this activity was not correlated with spermostasis. Rather, the latter was associated with alkylation of two major sperm tail proteins that were identified as A Kinase-Anchoring Proteins (AKAP3 and AKAP4) by mass spectrometry. As a consequence of disrupted AKAP function, the abilities of cAMP to drive protein kinase A-dependent activities in the sperm tail, such as the activation of SRC and the consequent stimulation of tyrosine phosphorylation, were suppressed. Furthermore, analysis of microbicidal activity using Chlamydia muridarum revealed powerful inhibitory effects at the same low micromolar doses that suppressed sperm movement. In this case, the microbicidal action was associated with alkylation of Major Outer Membrane Protein (MOMP), a major chlamydial membrane protein. Taken together, these results have identified for the first time a novel set of cellular targets and chemical principles capable of providing simultaneous defense against both fertility and the spread of sexually transmitted disease.

Risk of falls, injurious falls, and other injuries resulting from visual impairment among older adults with age-related macular degeneration

Purpose: Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment among older adults. This study explored the relationship between AMD, falls risk and other injuries and identified visual risk factors for these adverse events. Methods: Participants included 76 community-dwelling individuals with a range of severity of AMD (mean age, 77.0±6.9 years). Baseline assessment included binocular visual acuity, contrast sensitivity and merged visual fields. Participants completed monthly falls and injury diaries for one year following the baseline assessment. Results: Overall, 74% of participants reported having either a fall, injurious fall or other injury. Fifty-four percent of participants reported a fall and 30% reported more than one fall; of the 102 falls reported, 63% resulted in an injury. Most occurred outdoors (52%), between late morning and late afternoon (61%) and when navigating on level ground (62%). The most common non-fall injuries were lacerations (36%) and collisions with an object (35%). Reduced contrast sensitivity and visual acuity were associated with increased fall rate, after controlling for age, gender, cognitive function, cataract severity and self-reported physical function. Reduced contrast sensitivity was the only significant predictor of falls and other injuries. Conclusion: Among older adults with AMD, increased visual impairment was significantly associated with an increased incidence of falls and other injuries. Reduced contrast sensitivity was significantly associated with increased rates of falls, injurious falls and injuries, while reduced visual acuity was only associated with increased falls risk. These findings have important implications for the assessment of visually impaired older adults.