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1.
J Appl Microbiol ; 122(4): 940-952, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28092137

ABSTRACT

AIMS: The aim of this work was to isolate novel lignin-degrading organisms. METHODS AND RESULTS: Several pure cultures of bacteria that degrade lignin were isolated from bacterial consortia developed from decaying biomass. Among the isolates, Rhizobium sp. strain YS-1r (closest relative of Rhizobium petrolearium strain SL-1) was explored for its lignin-degrading ability. Microcosm studies showed that strain YS-1r was able to degrade a variety of lignin monomers, dimers and also native lignin in switchgrass and alfalfa. The isolate demonstrated lignin peroxidase (LiP) activity when grown on alkali lignin, p-anisoin, switchgrass or alfalfa, and only negligible activity was measured in glucose-grown cells suggesting inducible nature of the LiP activity. Analysis of the strain YS-1r genome revealed the presence of a variety of genes that code for various lignin-oxidizing, H2 O2 -producing as well as polysaccharide-hydrolysing enzymes. CONCLUSIONS: This study shows both the genomic and physiological capability of bacteria in the genus Rhizobium to metabolize lignin and lignin-like compounds. This is the first detailed report on the lignocellulose-degrading ability of a Rhizobium species and thus this study expands the role of alpha-proteobacteria in the degradation of lignin. SIGNIFICANCE AND IMPACT OF THE STUDY: The organism's ability to degrade lignin is significant since Rhizobia are widespread in soil, water and plant rhizospheres and some fix atmospheric nitrogen and also have the ability to degrade aromatic hydrocarbons.


Subject(s)
Lignin/metabolism , Rhizobium/metabolism , Biomass , Medicago sativa/metabolism , Panicum/metabolism , Rhizobium/genetics , Rhizobium/isolation & purification
2.
Occup Med (Lond) ; 65(7): 549-51, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26106127

ABSTRACT

BACKGROUND: Previous research has examined how age and health can shape workability (WA). This study seeks to explore how a lack of WA (inability) may affect the health of the employee. AIMS: To explore the effects of work inability on mental wellbeing among therapeutic prison officers. METHODS: An anonymous cross-sectional study of prison officers conducted in a category B English prison using the Work Ability Index (WAI) and General Health Questionnaire-28 (GHQ). RESULTS: Fifty-seven officers (59%) participated and of those 95% achieved GHQ caseness. Officers with poorer WA reported significantly higher GHQ scores. Work inability for mental demands had significant associations with anxiety (ß = -0.58, 95% CI -4.21 to -1.88, particularly sleep loss; Pearson's r = -0.66). CONCLUSIONS: Our findings present clear associations between poor WA and its impact upon mental wellbeing. The results of this study may help to focus on areas for intervention such as improving WA and promoting mental wellbeing.


Subject(s)
Anxiety/etiology , Mental Health , Occupational Exposure , Occupations , Prisons , Sleep Wake Disorders/etiology , Work , Adult , Aged , Counselors , Cross-Sectional Studies , Employment , England , Female , Humans , Male , Middle Aged , Occupational Health , Stress, Psychological/complications , Surveys and Questionnaires , Work Capacity Evaluation , Young Adult
3.
Int J Obes (Lond) ; 38(4): 591-6, 2014 Apr.
Article in English | MEDLINE | ID: mdl-23846452

ABSTRACT

BACKGROUND: There is some evidence for a bidirectional association between obesity and depression. However, studies examining weight change and depression are scarce and report inconsistent findings. OBJECTIVE: The objective was to investigate the relationship between average annual percentage weight change and depression in mid-aged women. DESIGN: This was a prospective cohort study. SUBJECTS: A total of 8246 women aged 45-50 years at baseline participating in the Australian Longitudinal Study on Women's Health were surveyed every 3 years over a 12-year period. Information on body mass index and depression was collected at each survey. We used regression models to investigate the effect of weight change predicting depression and vice versa, by calculating odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Weight gain was associated with an increased risk of prevalence (OR 1.39, 95% CI 1.25-1.56) and incidence (OR 1.30, 95% CI 1.14-1.49) of depression. However, in time-lagged analyses, where weight change between the two preceding surveys was used to predict incidence of depression at the current survey, no statistically significant associations with depression were found. Compared with women without depression, women with prevalent and incident depression had an increased risk of weight gain (OR 1.29, 95% CI 1.19-1.40 and OR 1.20, 95% CI 1.05-1.38, respectively). When incidence of depression was lagged with respect to weight change between the two subsequent surveys, depression remained associated with an increased risk (OR 1.19, 95% CI 1.00-1.41) of gaining weight. CONCLUSION: These findings suggest that depression may cause weight gain over the next 3 years, but that weight change (loss or gain) may not lead to depression. Further research at shorter intervals, perhaps 6 monthly or yearly is needed to ascertain whether weight change is an independent predictor of depression in the shorter term.


Subject(s)
Aging , Depression/epidemiology , Weight Gain , Adult , Aged , Aged, 80 and over , Aging/psychology , Australia , Body Mass Index , Female , Humans , Longitudinal Studies , Middle Aged , Prevalence , Prospective Studies , Risk Factors , Women's Health
4.
Occup Med (Lond) ; 63(7): 479-84, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24038508

ABSTRACT

BACKGROUND: In the light of the Winsor review, UK police forces have been urged to use fitness tests as large-scale cost-effective measures of officers' fitness to work. One test is the Gender-Neutral Timed Obstacle Course (GeNTOC), which must be completed within 3min 45 s, regardless of sex. AIMS: To investigate if obstacle courses, mimicking a range of police-type activities, can provide a suitable and valid basis for identifying fit and unfit officers and if any other factors may influence test performances. METHODS: Five years of GeNTOC records were randomly sampled, providing data for 1701 officers. Pass/fail rates were analysed alongside demographics and obstacle performance. RESULTS: Of 1701 candidates, 24% (397) failed GeNTOC (7 and 42% of males and females, respectively). Females failed in two specific obstacles significantly more often than males: the 'body drag' and 'gate weave'. Errors made on these obstacles alone accounted for 49% of obstacle errors made by females. GeNTOC success was significantly associated with candidates who were male, younger, taller, heavier and of lower body mass index (BMI). Of all candidates, 42% were overweight, and 8% were obese. CONCLUSIONS: The GeNTOC was not a useful screening tool and worked independently of BMI groups. Too few candidates were appropriately screened out; too many of those failing were female; and too many who passed were overweight or obese. GeNTOC was unfair to female candidates and favoured overweight or obese males. Recommendations are made to adopt alternative fitness tests or to modify the GeNTOC obstacles, testing procedures and data collection.


Subject(s)
Body Mass Index , Exercise Test/standards , Physical Fitness , Police , Adult , Age Factors , Body Height , Body Weight , Female , Humans , Male , Movement , Obesity/epidemiology , Overweight/epidemiology , Reproducibility of Results , Sex Factors , United Kingdom/epidemiology , Work , Young Adult
5.
Diabetologia ; 55(11): 2938-45, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22893029

ABSTRACT

AIMS/HYPOTHESIS: The aim of this study was to explore the relationships between type 2 diabetes mellitus, area-based socioeconomic status (SES) and cardiovascular disease mortality in Scotland. METHODS: We used an area-based measure of SES, Scottish national diabetes register data linked to mortality records, and general population cause-specific mortality data to investigate the relationships between SES, type 2 diabetes and mortality from ischaemic heart disease (IHD) and cerebrovascular disease (CbVD), for 2001-2007. We used negative binomial regression to obtain age-adjusted RRs of mortality (by sex), comparing people with type 2 diabetes with the non-diabetic population. RESULTS: Among 216,652 people aged 40 years or older with type 2 diabetes (980,687 person-years), there were 10,554 IHD deaths and 4,378 CbVD deaths. Age-standardised mortality increased with increasing deprivation, and was higher among men. IHD mortality RRs were highest among the least deprived quintile and lowest in the most deprived quintile (men: least deprived, RR 1.94 [95% CI 1.61, 2.33]; most deprived, RR 1.46 [95% CI 1.23, 1.74]) and were higher in women than men (women: least deprived, RR 2.84 [95% CI 2.12, 3.80]; most deprived, RR 2.04 [95% CI 1.55, 2.69]). A similar, weaker, pattern was observed for cerebrovascular mortality. CONCLUSIONS/INTERPRETATION: Absolute risk of cardiovascular mortality is higher in people with diabetes than in the non-diabetic population and increases with increasing deprivation. The relative impact of diabetes on cardiovascular mortality differs by SES, and further efforts to reduce cardiovascular risk both in deprived groups and people with diabetes are required. Prevention of diabetes may reduce socioeconomic health inequalities.


Subject(s)
Cardiovascular Diseases/economics , Cardiovascular Diseases/mortality , Diabetes Mellitus, Type 2/economics , Diabetes Mellitus, Type 2/mortality , Social Class , Adult , Age Distribution , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Models, Statistical , Prevalence , Registries/statistics & numerical data , Risk Factors , Scotland/epidemiology , Sex Distribution
6.
Occup Med (Lond) ; 61(6): 385-94, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21921124

ABSTRACT

BACKGROUND: Remote and mobile workers (RMWs), people who spend the majority of work time away from a home or office base, are estimated to number 1 million in the UK and Ireland. A number of advantages and challenges have been identified with this way of working but little is known about the impact of this type of work on the health and well-being of RMWs. AIMS: To identify any potential health or psychosocial effects associated with remote and mobile working, identify ergonomic factors that impact on this group and ascertain the effect of organizational or management factors that influence this occupational group. METHODS: A systematic review methodology was used and a search strategy developed including keywords, which were used to search electronic databases and websites. Data were then extracted from included papers and quality assessed. RESULTS: Initial searches identified 280 references but only 11 papers reached the inclusion criteria. Health effects identified included musculoskeletal symptoms associated with higher mileage and more time in a vehicle but a number of vehicle design issues were found to improve symptoms. Psychosocial factors including high demands were also found but better mental health was associated with higher mileage and more time with clients. There was a lack of substantive evidence in relation to managing this group. CONCLUSIONS: There is little research currently available on the general health of RMWs and future research should examine this further and focus on general health and access to support services.


Subject(s)
Employment , Occupational Diseases , Occupational Health , Employment/organization & administration , Employment/psychology , Health Status , Humans , Musculoskeletal Diseases/epidemiology , Musculoskeletal Diseases/etiology , Occupational Diseases/epidemiology , Occupational Diseases/etiology , Transients and Migrants/psychology
7.
Neurology ; 77(2): 158-67, 2011 Jul 12.
Article in English | MEDLINE | ID: mdl-21715706

ABSTRACT

OBJECTIVE: We performed a systematic review and meta-analyses to assess the evidence for genetic associations with brain microbleeds (BMBs). METHODS: We sought all published studies of the association between any genetic polymorphism and BMBs studied in a total of >100 people. We critically appraised studies, and calculated pooled odds ratios (ORs) using the generic inverse variance fixed effects method. We used I² and χ² statistics to assess heterogeneity, and fail-safe N estimates to assess the robustness of our results. RESULTS: Only the APOE ε2/3/4 polymorphism had been studied in >100 people (10 studies, 7,351 participants). Compared with people with the ε3/ε3 genotype, carriers of the ε4 allele (ε4+) were statistically significantly more likely to have BMBs in any location (ε4+ vs ε3/ε3: pooled OR 1.22, 95% confidence interval [CI] 1.05-1.41, p = 0.01). For strictly lobar BMBs, this association appeared slightly stronger (ε4+ vs ε3/ε3: pooled OR 1.35, 95% CI 1.10-1.66, p = 0.005). The association of ε4+ genotypes with strictly lobar BMBs was reasonably robust to potential publication and reporting biases. CONCLUSIONS: Given the known associations of APOE alleles with lobar intracerebral hemorrhage and cerebral amyloid angiopathy, these findings support the concept that strictly lobar BMBs may be an imaging biomarker of cerebral amyloid angiopathy.


Subject(s)
Apolipoproteins E/genetics , Brain/pathology , Cerebral Hemorrhage/genetics , Polymorphism, Genetic , Genome-Wide Association Study , Genotype , Humans , Odds Ratio
9.
Equine Vet J Suppl ; (38): 606-12, 2010 Nov.
Article in English | MEDLINE | ID: mdl-21059068

ABSTRACT

REASONS FOR PERFORMING STUDY: Sildenafil, a phosphodiesterase-5 inhibitor vasodilator, increases cGMP concentrations by inhibiting enzymatic degradation. Marketed to treat erectile dysfunction in men, it also reduces pulmonary arterial pressure (PAP). Because it reduces PAP, sildenafil may enhance performance and/or prevent exercise induced-pulmonary haemorrhage (EIPH). OBJECTIVE: To determine if sildenafil citrate administration altered commonly measured indices of performance or reduced EIPH in exercised horses. METHODS: Thirteen athletically conditioned Thoroughbred horses (2 mares and 11 geldings, age 3-12 years) were administered sildenafil citrate or placebo in 2 crossover design exercise testing studies. In a step-wise test to exhaustion, inspired/expired gas analysis, blood lactate, heart rate, runtime and bronchoalveolar lavage (BAL) cytology were measured. In a 13 m/s test to exhaustion, blood lactate, heart rate, runtime, BAL cytology and pulmonary arterial pressure were measured. Data were analysed with paired and unpaired t tests, one-way ANOVA and Tukey's pair-wise multiple comparison and Friedman repeated measure analysis of variance on ranks. RESULTS: The administration of sildenafil did not alter mean inspired/expired gas measurements, plasma lactate concentrations or acute pulmonary haemorrhage in either exercise test or pulmonary arterial pressure measurement in the 13 m/s trial. Heart rates in both stress tests were significantly different at submaximal speeds and during the early recovery period. Run time was not affected by sildenafil administration in the step-wise trial (P = 0.622) or in the 13 m/s trial (P = 0.059). CONCLUSIONS: Sildenafil did not alleviate pulmonary haemorrhage or enhance performance-related indices in these trials. Sildenafil administration altered cardiovascular adaptation to intense exercise as evidenced by altered heart rates at submaximal speeds and post exercise. The effect of these alterations on other performance perimeters was not evident.


Subject(s)
Heart Rate/drug effects , Phosphodiesterase 5 Inhibitors/pharmacology , Physical Endurance/drug effects , Piperazines/pharmacology , Pulmonary Gas Exchange/drug effects , Sulfones/pharmacology , Animals , Blood Pressure/drug effects , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/cytology , Cross-Over Studies , Female , Horses , Lactic Acid/blood , Male , Phosphodiesterase 5 Inhibitors/administration & dosage , Physical Conditioning, Animal , Piperazines/administration & dosage , Purines/administration & dosage , Purines/pharmacology , Sildenafil Citrate , Sulfones/administration & dosage
10.
Am J Gastroenterol ; 105(3): 525-39, 2010 Mar.
Article in English | MEDLINE | ID: mdl-19997092

ABSTRACT

OBJECTIVES: Adherence is generally associated with improved treatment outcomes. Risk factors for non-adherence must be understood to improve adherence. A systematic review was undertaken to determine which variables were consistently associated with non-adherence to oral medication in inflammatory bowel disease (IBD). METHODS: The databases EMBASE, Medline, and PsycINFO were searched for titles relating to adherence, medication, and IBD (1980-2008). Primary, quantitative studies were included if they concerned adult patients with IBD, measured adherence to oral medication, and measured characteristics associated with adherence. The resulting 17 papers were independently reviewed by two researchers who also assessed their quality according to pre-defined criteria. The main outcome was the frequency with which demographic, clinical, treatment, and psychosocial variables were found to be statistically significantly associated with non-adherence. RESULTS: Non-adherence rates ranged from 7 to 72%, with most studies reporting that 30-45% of patients were non-adherent. No demographic, clinical, or treatment variables were consistently associated with non-adherence. Psychological distress and patients' beliefs about medications were both related to non-adherence in four out of five studies, and doctor-patient discordance was associated with non-adherence in two out of three studies. CONCLUSIONS: This is the largest review of factors associated with non-adherence in IBD. Demographic, clinical, and treatment variables were not consistently associated with non-adherence. Psychological distress, patients' beliefs about medications, and doctor-patient discordance were associated with non-adherence. These findings call into question some of the conclusions of earlier reviews that did not take into account nonsignificant findings. Practical suggestions for gastroenterologists and future research are discussed.


Subject(s)
Gastrointestinal Agents/administration & dosage , Inflammatory Bowel Diseases/drug therapy , Patient Compliance , Adult , Humans , Inflammatory Bowel Diseases/psychology , Patient Compliance/psychology , Physician-Patient Relations , Risk Factors , Treatment Refusal
11.
J Neurol Neurosurg Psychiatry ; 77(11): 1244-52, 2006 Nov.
Article in English | MEDLINE | ID: mdl-16690694

ABSTRACT

OBJECTIVE: To determine whether evidence from observational studies supports the widely held belief that hypertension is more commonly a risk factor for deep than for lobar supratentorial intracerebral haemorrhage. METHODS: Studies comparing the frequency of hypertension as a risk factor for deep versus lobar supratentorial intracerebral haemorrhage, excluding haemorrhages with identified secondary causes, were identified and subjected to a meta-analysis. The effects of predefined methodological quality criteria on the results were assessed and other sources of bias were considered. RESULTS: The pooled result from all 28 included studies (about 4000 patients) found hypertension to be about twice as common in patients with deep as in those with lobar haemorrhage (odds ratio (OR) 2.10, 95% confidence interval (95% CI) 1.82 to 2.42), but there was significant heterogeneity between studies. The pooled OR was less extreme for studies that used a pre-stroke definition of hypertension, were population based or included first-ever strokes only. In the three studies meeting all criteria (601 patients), deep haemorrhage was associated with a smaller, statistically significant excess of hypertension (OR 1.50, 95% CI 1.09 to 2.07). The OR for studies confined to younger patients seemed to be more extreme (12.32, 95% CI 6.13 to 24.77), but none of these studies fulfilled our methodological quality criteria. Additional, unquantified sources of bias included uncertainty about whether those doctors reporting brain scans were blind to hypertension status, uncertain reliability of the classification of haemorrhage location and variable rates of investigation for secondary causes. CONCLUSIONS: An excess of hypertension was found in patients with deep versus lobar intracerebral haemorrhages without an identified secondary cause, but this may be due to residual, unquantified methodological biases.


Subject(s)
Cerebral Hemorrhage/etiology , Cerebral Hemorrhage/pathology , Hypertension/complications , Brain/pathology , Humans , Hypertension/epidemiology , Odds Ratio , Risk Factors
13.
Equine Vet J Suppl ; (36): 262-6, 2006 Aug.
Article in English | MEDLINE | ID: mdl-17402429

ABSTRACT

REASONS FOR PERFORMING STUDY: Adrenergic activity accompanies intense exercise and mediates physiological and metabolic responses to exercise. Guanabenz, an antihypertensive drug marketed for human usage, depresses brain vasomotor and cardioaccelerator centres, blocks peripherally adrenergic neurons and is reportedly used as a calming agent in horses but little is known of its effects in the species. OBJECTIVES: To determine if guanabenz induces measurable signs of adrenergic suppression on fit Thoroughbred horses undergoing intense exercise. METHODS: In a random crossover design, 12 exercise conditioned Thoroughbred horses each received guanabenz (0.08 mg/kg bwt i.v.) and placebo at 3-week intervals. An incremental exercise test to exhaustion on a treadmill followed treatment by 1 h. Heart rate, oxygen consumption, carbon dioxide production, plasma lactate, catecholamines, adrenocorticotropic hormone (ACTH) and cortisol, and time to fatigue were monitored. Statistical analysis was performed using mixed-effects linear modelling. RESULTS: Mean heart rate during the exercise period was lower in guanabenz-treated horses (P = 0.04). Mean concentrations of plasma cortisol (P = 0.02) and adrenaline (P = 0.03) were lower for guanabenz-treated horses during the exercise period. Mean run time was slightly but not significantly longer for guanabenz-treated horses, (P = 0.053). No significant effects of guanabenz administration were found for oxygen consumption, carbon dioxide production nor for plasma lactate, noradrenaline and ACTH concentrations. CONCLUSION: Guanabenz administration induced signs of adrenergic suppression including plasma cortisol and adrenaline concentrations and heart rate and may enhance endurance, but did not eliminate increases in hormone concentrations induced by exercise. Clear determination of a positive performance effect of adrenaline, but not noradrenaline, suppression is needed before clinical significance can be determined.


Subject(s)
Adrenergic alpha-Agonists/pharmacology , Guanabenz/pharmacology , Heart Rate/physiology , Horses/physiology , Physical Conditioning, Animal/physiology , Adrenocorticotropic Hormone/blood , Animals , Carbon Dioxide/blood , Cross-Over Studies , Epinephrine/blood , Exercise Test/veterinary , Female , Horses/blood , Hydrocortisone/blood , Male , Norepinephrine/blood , Oxygen Consumption , Time Factors
15.
Ann Occup Hyg ; 46(5): 455-63, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12176760

ABSTRACT

OBJECTIVES: Most studies to date on sound levels in entertainment establishments have concentrated on exposure levels for the attending public, rather than employees who may be at greater risk of hearing loss. Of particular concern are young employees. The aim of this pilot study was to (i) estimate typical sound levels in different areas where amplified music was played, (ii) measure temporary threshold shift (TTS) and (iii) estimate the dependence of hearing threshold shifts on measured noise levels. METHODS: This study focused on students working part-time (up to 16 h/week) in music bars and discotheques in a university entertainment venue. All 28 staff were invited to participate in the study. Pre- and post-exposure audiometry was used to determine hearing threshold at both high and low frequencies. Personal dosemeters and static measurements were made to assess noise levels and frequency characteristics. A questionnaire was used to determine patterns of noise exposure and attitudes to noise levels and hearing loss. RESULTS: Of the 28 student employees working in the three areas, 14 (50%) agreed to take part in the study, giving 21 pre- and post-shift audiograms. The mean personal exposure levels for security staff were higher than those of bar staff, with both groups exceeding 90 dB(A). The maximum peak pressure reading for security staff was 124 dB. Although TTS values were moderate, they were found to be highly significant at both low and high frequencies and for both ears. Twenty-nine per cent of subjects showed permanent hearing loss of more than 30 dB at either low or high frequencies. The correlation between TTS and personal exposure was higher at 4 kHz than the low and high frequencies. CONCLUSIONS: Contemporary music may be an important yet little considered contributor to total personal noise exposure, especially amongst young employees. Employees need to be better informed of risks of hearing loss and the need to report changes in hearing acuity. Suggestions are made on strategies for improving the assessment of noise exposure in entertainment venues.


Subject(s)
Auditory Fatigue , Hearing Loss, Noise-Induced/epidemiology , Music , Noise, Occupational , Adult , Audiometry , Humans , Leisure Activities , Pilot Projects , Schools
16.
Cancer Res ; 61(23): 8470-9, 2001 Dec 01.
Article in English | MEDLINE | ID: mdl-11731430

ABSTRACT

The failure and/or toxicity of conventional therapies for many types of human cancers underscore the need for development of safe and effective alternative treatments. Toward this goal, we describe the direct oncolytic activity of RNA-based vectors derived from poliovirus, termed replicons, which are genetically incapable of producing infectious virus. These replicons are cytopathic in vitro for human tumor cells originating from brain, breast, lung, ovary, and skin (melanoma). The cytopathic effects in a malignant glioma cell line were associated with nuclear DNA condensation, indicative of cells undergoing apoptosis. Injection of replicons into established xenograft flank tumors in scid mice resulted in oncolytic activity and extended survival. Inoculation of replicons into established intracranial xenograft tumors in scid mice resulted in tumor infection within 8 h and extended survival. Histological analysis revealed that replicons had infected tumor cells at the site of inoculation and, most importantly, diffused to infect tumor cells that had metastasized from the initial site of implantation. The wide spectrum of cytopathic activity for human tumors combined with effective distribution after in vivo inoculation establishes the therapeutic potential of poliovirus replicons for a variety of cancers.


Subject(s)
Neoplasms/therapy , Poliovirus/physiology , Replicon/physiology , Animals , Brain Neoplasms/pathology , Brain Neoplasms/therapy , Brain Neoplasms/virology , Cytopathogenic Effect, Viral , Glioma/pathology , Glioma/therapy , Glioma/virology , HeLa Cells , Humans , Mice , Mice, SCID , Neoplasms/pathology , Neoplasms/virology , Poliovirus/genetics , RNA, Viral/administration & dosage , RNA, Viral/genetics , Xenograft Model Antitumor Assays
17.
Hum Gene Ther ; 12(15): 1827-41, 2001 Oct 10.
Article in English | MEDLINE | ID: mdl-11589826

ABSTRACT

Poliovirus-based vectors (replicons) can be used for gene delivery to motor neurons of the CNS. In the current study, a replicon encoding green fluorescent protein (GFP) was encapsidated into authentic poliovirions, using established procedures. Intrathecal delivery of encapsidated replicons encoding GFP to the CNS of mice transgenic for the human poliovirus receptor did not result in any functional deficits as judged by behavioral testing. Histological analysis of the CNS of mice given a single intrathecal injection of poliovirus replicons encoding GFP revealed no obvious pathogenesis in neurons (or other cell types) within the CNS. The expression of GFP was confined to motor neurons throughout the neuroaxis; a time course of expression of GFP revealed that expression was detectable 24 hr postinoculation and returned to background levels by 120 hr postinoculation. A procedure was devised to allow repetitive inoculation of replicons within the same animal. Behavioral testing of animals that had received 6 to 13 independent inoculations of replicons revealed no functional deficits. Histological analysis of the CNS from animals that had received 6 to 13 sequential inoculations of replicons revealed no obvious abnormalities in neurons or other cell types in the CNS; expression of GFP was demonstrated in neurons 24 to 72 hr after the final inoculation of the replicon. Furthermore, there was no obvious inflammatory response in the CNS after the multiple inoculations. These studies establish the safety and efficacy of replicons for gene delivery to the CNS and are discussed with respect to use of replicons as new therapeutic strategies for spinal cord injuries and/or neurological diseases.


Subject(s)
Central Nervous System/metabolism , Gene Transfer Techniques , Genetic Therapy/methods , Neurons/metabolism , Poliovirus/genetics , Animals , Green Fluorescent Proteins , HeLa Cells , Humans , Injections, Spinal , Luminescent Proteins/metabolism , Mice , Mice, Transgenic , Microscopy, Fluorescence , Nervous System Diseases/therapy , Spinal Cord/cytology , Spinal Cord/pathology , Spinal Cord Injuries/therapy , Time Factors
18.
Occup Med (Lond) ; 51(4): 287-93, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11463874

ABSTRACT

The objective of this study was to compare the validity of the original weightings used by the Life Events Inventory (LEI) with those obtained from a contemporary occupational sample. Fifty male and 62 female manufacturing employees (age range 16-55 years) assigned scores to each item on a slightly modified version of the LEI scale. The current sample consistently assigned higher weights to events/items than did the original sample, but there was high agreement in terms of item ranking. Some distinct age and gender differences in scoring were apparent, and are discussed further. It was concluded that when separate weightings are employed for age and gender groups, the LEI remains a useful tool for quantifying background levels of stress in both workplace stress audits and epidemiological studies where statistical control for non-occupational sources of stress is required.


Subject(s)
Life Change Events , Occupational Diseases/etiology , Stress, Psychological/etiology , Adolescent , Adult , Age Factors , Female , Humans , Male , Middle Aged , Sex Factors
19.
Am J Vet Res ; 62(5): 775-8, 2001 May.
Article in English | MEDLINE | ID: mdl-11341402

ABSTRACT

OBJECTIVE: To determine the effect of a tongue-tie on upper airway mechanics in exercising horses. ANIMALS: 5 Standardbreds. PROCEDURE: Peak inspiratory and expiratory tracheal and pharyngeal pressures and airflow were measured while horses exercised on a treadmill with and without a tongue-tie. Respiratory rate was also measured. Horses ran at speeds that corresponded to 50 (HR50), 75, 90 (HR90), and 100% of maximal heart rate. The tongue-tie was applied by pulling the tongue forward out of the mouth as far as possible and tying it at the level of the base of the frenulum to the mandible with an elastic gauze bandage. Peak inspiratory and expiratory tracheal, pharyngeal, and translaryngeal resistance, minute ventilation, and tidal volume were calculated. Data were analyzed by use of 2-way repeated-measures ANOVA. For post hoc comparison of significant data, the Student-Newman-Keuls test was used. RESULTS: We were unable to detect significant differences between groups for peak inspiratory or expiratory tracheal or pharyngeal resistance, peak pressure, peak expiratory flow, tidal volume, respiratory rate, or minute ventilation. Horses that ran with a tongue-tie had significantly higher peak inspiratory flows, compared with horses that ran without a tongue-tie. In the post hoc comparison, this effect was significant at 4 m/s, HR50, and HR90. CONCLUSION AND CLINICAL RELEVANCE: Application of a tongue-tie did not alter upper respiratory mechanics in exercising horses and may be beneficial in exercising horses with certain types of obstructive dysfunction of the upper airways. However, application of a tongue-tie does not improve upper airway mechanics in clinically normal horses.


Subject(s)
Horses/physiology , Physical Conditioning, Animal/physiology , Respiration , Tongue/physiology , Animals , Cross-Over Studies , Female , Heart Rate/physiology , Male , Random Allocation , Respiratory Function Tests/veterinary
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