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The determinants of length of life are multifactorial and involve complex processes, most of which are not as yet understood completely. Tremendous advances have, however, been made in recent times in understanding some of the key molecular mechanisms that influence ageing and lifespan. Herein we highlight many of the more important findings and their potential clinical implications. Most of the intracellular factors involved in the ageing process, such as members of the sirtuin family, as well as insulin and insulin-like growth factor-I and their genes, are part of interconnected pathways. The manipulation of these and other genes in animal models can increase or decrease lifespan. Transcriptional and post-transcriptional regulatory mechanisms, some of which involve microRNAs, as well as modifications to chromatin and histones, can influence longevity. A decline in the function of stem cells might also be responsible for some aspects of mammalian ageing. Calorie restriction, polyphenols such as resveratrol, rapamycin, spermidine and angiotensin I converting enzyme inhibitor, are able to increase lifespan by modulation of branches of the longevity pathways. Molecular genetic studies of long-lived subjects have identified several potential candidate genes, but genetic research on ageing is in its infancy. Large genome-wide association studies should provide insights. Although new biomarkers for ageing and health, such as ones that might reveal telomere dysfunction, have been described, advances in the genetics and molecular biology of longevity will require interdisciplinary approaches if the much-hoped for success in alleviating the diseases of ageing, and an extension of both lifespan and healthspan is to be achieved.
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OBJECTIVES: It can be difficult to distinguish vestibular migraine (VM) from Meniere's disease (MD) in its early stages. Using vestibular-evoked myogenic potentials (VEMPs), we sought to identify test parameters that would help discriminate between these two vestibular disorders. METHODS: We first recorded ocular and cervical VEMPs (oVEMP/cVEMP) to air-conducted clicks and bone-conducted vibration in 30 control participants, 30 participants with clinically definite VM and 30 participants with clinically probable VM. Results were compared with a group of 60 MD patients from a previous study. oVEMPs and cVEMPs were then recorded at octave frequencies of 250 Hz to 2000 Hz in 20 controls and 20 participants each with clinically definite VM and MD. Inter-aural amplitude asymmetry ratios and amplitude frequency ratios were compared between groups. RESULTS: For click, tendon-hammer-tap and minishaker-tap VEMPs, there were no significant differences in reflex amplitudes or symmetry between controls, definite VM and probable VM. Compared with MD patients, participants with VM had significantly fewer reflex abnormalities for click-cVEMP, click-oVEMPs and minitap-cVEMPs. The ratio of cVEMP amplitude generated by tone bursts at a frequency of 0.5 kHz to that generated by 1 kHz was significantly lower for MD affected ears than for VM or controls ears. cVEMP asymmetry ratios for 0.5 kHz tone bursts were significantly higher for MD than VM. CONCLUSIONS: The 0.5/1 kHz frequency ratio, 0.5 kHz asymmetry ratio and caloric test combined, separated MD from VM with a sensitivity of 90.0% and specificity of 70.0%.
Description:
Background Mutations in LRRK2, the gene that encodes leucine-rich repeat kinase 2, are a cause of Parkinson's disease (PD). The International LRRK2 Consortium was established to answer three key clinical questions: can LRRK2-associated PD be distinguished from idiopathic PD; which mutations in LRRK2 are pathogenic; and what is the age-specific cumulative risk of PD for individuals who inherit or are at risk of inheriting a deleterious mutation in LRRK2? Methods Researchers from 21 centres across the world collaborated on this study. The frequency of the common LRRK2 Gly2019Ser mutation was estimated on the basis of data from 24 populations worldwide, and the penetrance of the mutation was defined in 1045 people with mutations in LRRK2 from 133 families. The LRRK2 phenotype was defined on the basis of 59 motor and non-motor symptoms in 356 patients with LRRK2-associated PD and compared with the symptoms of 543 patients with pathologically proven idiopathic PD. Findings Six mutations met the consortium's criteria for being proven pathogenic. The frequency of the common LRRK2 Gly2019Ser mutation was 1% of patients with sporadic PD and 4% of patients with hereditary PD; the frequency was highest in the middle east and higher in southern Europe than in northern Europe. The risk of PD for a person who inherits the LRRK2 Gly2019Ser mutation was 28% at age 59 years, 51% at 69 years, and 74% at 79 years. The motor symptoms (eg, disease severity, rate of progression, occurrence of falls, and dyskinesia) and non-motor symptoms (eg, cognition and olfaction) of LRRK2-associated PD were more benign than those of idiopathic PD. Interpretation Mutations in LRRK2 are a clinically relevant cause of PD that merit testing in patients with hereditary PD and in subgroups of patients with PD. However, this knowledge should be applied with caution in the diagnosis and counselling of patients.
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Behavioural epidemiology in health promotion has been defined as having five phases: establishing links between behaviours and health; developing measures of the behaviour; identifying influences on the behaviour; evaluating interventions to change the behaviour; and translating the research into practice. This article outlines some recent developments in the application of behavioural epidemiology to the issue of sport participation in Australia and its consequential health benefits.
Description:
Background: Escherichia coli is the commonest cause of community and nosocomial urinary tract infection (UTI). Antibiotic treatment is usually empirical relying on susceptibility data from local surveillance studies. We therefore set out to determine levels of resistance to 8 commonly used antimicrobial agents amongst all urinary isolates obtained over a 12 month period. Methods: Antimicrobial susceptibility to ampicillin, amoxicillin/ clavulanate, cefalexin, ciprofloxacin, gentamicin, nitrofurantoin, trimethoprim and cefpodoxime was determined for 11,865 E. coli urinary isolates obtained from community and hospitalised patients in East London. Results: Nitrofurantoin was the most active agent (94% susceptible), followed by gentamicin and cefpodoxime. High rates of resistance to ampicillin (55%) and trimethoprim (40%), often in combination were observed in both sets of isolates. Although isolates exhibiting resistance to multiple drug classes were rare, resistance to cefpodoxime, indicative of Extended spectrum
Description:
Background: Escherichia coli is the commonest cause of community and nosocomial urinary tract infection (UTI). Antibiotic treatment is usually empirical relying on susceptibility data from local surveillance studies. We therefore set out to determine levels of resistance to 8 commonly used antimicrobial agents amongst all urinary isolates obtained over a 12 month period. Methods: Antimicrobial susceptibility to ampicillin, amoxicillin/ clavulanate, cefalexin, ciprofloxacin, gentamicin, nitrofurantoin, trimethoprim and cefpodoxime was determined for 11,865 E. coli urinary isolates obtained from community and hospitalised patients in East London. Results: Nitrofurantoin was the most active agent (94% susceptible), followed by gentamicin and cefpodoxime. High rates of resistance to ampicillin (55%) and trimethoprim (40%), often in combination were observed in both sets of isolates. Although isolates exhibiting resistance to multiple drug classes were rare, resistance to cefpodoxime, indicative of Extended spectrum
Description:
In this study, the recently introduced International Classification of Disease, 10th revision, code for hot tap water scalds was used to examine the epidemiology of these cases and other scalds injuries in children younger than 5 years of age and adults aged 65 years and older. Although the trunk was the most common area in which scalds occurred, young children were more likely to sustain head and neck scalds (15%, 95% confidence interval 10.8-18.3) because of hot tap water than older people (2%, 95% confidence interval 0.2-4.4). Hospital separation rates for hot water scalds decreased significantly during the study period in both boys ([chi]2 = 15.6, df = 1, P < .001) and girls ([chi]2 = 5.6, df = 1, P < .001) who were younger than 5 years of age, which might be attributable to the introduction of new standards regulating the provision of hot tap water to various buildings. The severity of scalds cases did not seem to be correlated with the length of hospital stay, which remained unchanged in both age groups.
Description:
Background The study examined the measurement equivalence for teacher ratings across Malaysian Malay, Chinese and Indian children. Methods Malaysian teachers completed ratings of the ODD symptoms for 574 Malay, 247 Chinese and 98 Indian children. Results The results supported the equivalences for the configural, metric, and error variances models, and the equivalences for ODD latent variances and mean scores. Discussion Together, these findings suggest good support for measurement and structural equivalences of the ODD symptoms across these ethnic groups. The theoretical and clinical implications of the findings for cross-cultural equivalence of the ODD symptoms are discussed.
Description:
Background The study examined the measurement equivalence for teacher ratings across Malaysian Malay, Chinese and Indian children. Methods Malaysian teachers completed ratings of the ODD symptoms for 574 Malay, 247 Chinese and 98 Indian children. Results The results supported the equivalences for the configural, metric, and error variances models, and the equivalences for ODD latent variances and mean scores. Discussion Together, these findings suggest good support for measurement and structural equivalences of the ODD symptoms across these ethnic groups. The theoretical and clinical implications of the findings for cross-cultural equivalence of the ODD symptoms are discussed.
Description:
FRATs are designed to identify both persons at high risk of falls and to allow for cost-effective targeting of fall prevention strategies. This study compares two FRATs (BHS FRAT and TNH-STRATIFY) for accuracy of predicting falls and targeting of fall prevention strategies in a sub-acute hospital. Comparisons of retrospective audit data over two periods (use of the BHS-FRAT; post TNH-STRATIFY implementation) were used in the evaluation (n=362). Inter-rater reliability of the TNH-STRATIFY was evaluated from independent assessment by two nurses for 30 sub-acute patients and using intraclass correlation coefficient (ICC2,1). Event rate (ER) and standard measures of predictive accuracy were calculated for both FRATs. The proportions of patients with documented fall prevention strategies addressing identified fall risk factors were compared between audit phases. The TNH-STRATIFY had high inter-rater reliability (ICC2,1=0.96). The BHS-FRAT and TNH-STRATIFY demonstrated poor predictive accuracy using recommended high risk cut-off scores, with low specificityER (0.07 and 0.13 respectively) and very low Youden IndexER (0.04 and 0.07 respectively), although these measures improved using modified cut-off scores. Positive and negative predictive values were moderate for the BHS-FRAT (0.51, 0.64) and TNH-STRATIFY (0.52, 0.61). The falls rate and proportion of recurrent fallers did not change between audit phases. Implementation rates for prevention strategies for key risk factors were higher following implementation of the TNH-STRATIFY. The results indicated that the TNH-STRATIFY, combined with associated nursing care plan falls documentation, improved the targeting of prevention strategies for key risk factors such as cognitive impairment, incontinence and mobility impairment.
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BACKGROUND: This study evaluated the measurement invariance and agreement across parent and teacher ratings of the DSM-IV-TR oppositional defiant disorder (ODD) symptoms. METHOD: Malaysian parents and teachers of 934 children (between 6 and 11 years of age) completed rating scales comprising the ODD symptoms. RESULTS: Findings showed support for full measurement invariance (configural, metric and thresholds). Additional results indicated low parent-teacher agreement for all symptoms. DISCUSSION: The theoretical and clinical and implications of these findings are discussed.
One session of high-intensity interval training (HIIT) every 5 days, improves muscle power but not static balance in lifelong sedentary ageing men : A randomized controlled trial