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1.
BMC Med Res Methodol ; 19(1): 134, 2019 06 28.
Article in English | MEDLINE | ID: mdl-31253087

ABSTRACT

BACKGROUND: Clinical guidelines produced in developed nations may not be appropriate in resource-constrained environments, due to differences in cultural, societal, economic and policy contexts. The purpose of this article is to describe an innovative and resource-efficient method to develop a clinical practice guideline (CPG), using the CPG contextualisation approach. METHODS: The four phased contextualisation framework was applied to produce a contextualised, multidisciplinary CPG for the primary health care of adults with chronic musculoskeletal pain (CMSP) in the South African context. The four phases were: a contextual analysis, evidence synthesis, contextual integration and external evaluation. Qualitative methodology was used to investigate context factors influencing health care in this environment. A systematic review was conducted to identify current, high-quality CPGs on the topic, and to synthesise a core set of clinical recommendations from the CPGs. Consensus methods were used to integrate context information with recommendations. A multidisciplinary panel of local experts authenticated and contextualised recommendations. The resultant CPG was externally reviewed using a survey. RESULTS: The results from the contextual analysis phase indicated a wide range of contextual factors that could influence the applicability and implementability of the recommendations, including: the personal characteristics of the patient and clinician, social and environmental circumstances, healthcare interventions available, and healthcare system factors. During phase two, six existent high quality CPGs were identified and a core set of multidisciplinary recommendations were sourced from them. The contextual integration phase produced the validated recommendations, accompanied by its underpinning body of evidence and context specific information. The outcome of phase four (external review) was that the recommendations were confirmed as relevant for the intended setting. CONCLUSION: CPG contextualisation was found to be a practical approach to develop a contextualised multidisciplinary CPG for the primary health care of adults with CMSP in a South African setting. The contextualisation approach enhanced the integration of multiple stakeholder perspectives and highlighted the importance of considering clinical, social and economic complexities during CPG development. Attention to contextual information is advocated to enhance the uptake of CPG recommendations, particularly in resource constrained settings. TRIAL REGISTRATION: Health Research Ethics Committee of Stellenbosch University, South Africa (S14/01/018); the review protocol was registered on PROSPERO (registration number CRD42015022098 ).


Subject(s)
Delivery of Health Care/methods , Diffusion of Innovation , Information Dissemination/methods , Musculoskeletal Pain/prevention & control , Practice Guidelines as Topic/standards , Adult , Chronic Disease , Humans , Primary Health Care/methods , Qualitative Research , South Africa
2.
BJOG ; 127(2): 300, 2020 01.
Article in English | MEDLINE | ID: mdl-31446672
3.
J Hum Nutr Diet ; 27(6): 626-31, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24387134

ABSTRACT

BACKGROUND: An understanding of the reproducibility of body composition measurements is essential for effective intervention studies. Air displacement plethysmography (ADP) and bioelectrical impedance (BIA) are two easy-to-use measures of body composition. The present study aimed to assess the reproducibility of ADP and BIA and compare them with each other, as well as with skinfold measurement. METHODS: Forty-one participants were tested on two occasions following an overnight fast. On test day 1, participants' height, weight and % body fat (BF) were measured using ADP and BIA. Measurements were replicated to assess the within-day reproducibility. On test day 2, participants were again tested using ADP and BIA and had skinfold measurements taken. Three skinfold equations for BF calculation were applied. Comparisons of within- and between-day reproducibility and between measurement techniques were completed using Pearson correlations and Bland-Altman analysis. RESULTS: Both Pearson correlation and Bland-Altman analysis showed good within- and between-day relationships and agreement for BF from ADP and BIA measurements. The two methods had a high correlation between them; however, the mean difference between the two was 3.1% (4.1%). From the skinfold equations used, the best agreement with ADP had a mean difference of 0.3% (0.8%) and, with BIA, had mean differences of 1.9% (4.2%). CONCLUSIONS: The data indicate that ADP and BIA cannot be used interchangeably, although both measurements had good within- and between-day agreement.


Subject(s)
Adipose Tissue , Anthropometry/methods , Body Composition , Electric Impedance , Plethysmography/methods , Adult , Female , Humans , Male , Reproducibility of Results , Skinfold Thickness , Young Adult
4.
J Anat ; 223(4): 311-20, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23930967

ABSTRACT

The development of intramembranous bone is a dynamic and complex process requiring highly coordinated cellular activities. Although the literature describes the detailed cellular dynamics of early mesoderm-derived endochondral bone, studies regarding neural crest-derived intramembranous bone have failed to keep pace. We analyzed the development of chick scleral ossicles from the onset of osteoid deposition to mineralization at morphological, histological, and ultrastructural levels. We find that the mesenchymal condensations from which ossicles develop change their shape from ellipsoidal to trapezoidal concurrent with an increase in size. Furthermore, the size of an ossicle is dependent upon its time of induction. Our histological analyses of condensation growth reveal cell migration and osteoid secretion as key cellular processes determining condensation size; these processes occur concomitantly to increase both the area and thickness of condensations. We also describe the formation of the zone of overlap between ossicles and conclude that the process is similar to that of cranial suture formation. Finally, transmission electron microscopy of early condensations demonstrates that early osteoblasts secrete collagen parallel to the long axis of the condensation. This study elucidates fundamental mechanisms of intramembranous bone development at the cellular level, furthering our knowledge of this important process among vertebrates.


Subject(s)
Bone Development/physiology , Sclera/embryology , Animals , Chick Embryo , Microscopy, Electron , Osteoblasts/ultrastructure , Osteogenesis/physiology , Sclera/cytology
5.
Scand J Med Sci Sports ; 23(5): 645-50, 2013 Oct.
Article in English | MEDLINE | ID: mdl-22299663

ABSTRACT

Research suggests that lead climbing is both physiologically and psychologically more stressful than top rope climbing for intermediate performers. This observation may not be true for advanced climbers, who train regularly on lead routes and are accustomed to leader falls. The aim of this study was to compare the psychophysiological stresses of lead and top rope on-sight ascents in advanced rock climbers. Twenty-one climbers (18 men and three women) ascended routes near or at the best of their ability (22 Ewbank). Psychological stress was measured preclimb using the Revised Comparative State Anxiety Inventory (CSAI-2R). Plasma cortisol was sampled at six intervals. The volume of oxygen (VO2 ) and heart rate (Hr) were measured throughout the climbs. No significant differences were found in self-confidence, somatic, or cognitive anxiety between the conditions lead and top rope. No significant differences in plasma cortisol concentration were found between any time points. No significant relationships were found between cortisol and any CSAI-2R measures. No significant differences were found between conditions for VO2 or blood lactate concentration. During the lead climb, Hr was significantly elevated during the last part of the route. Findings suggest that advanced rock climbers do not find lead climbing to be more stressful than top rope climbing during an on-sight ascent.


Subject(s)
Mountaineering/psychology , Physical Endurance/physiology , Stress, Physiological/physiology , Stress, Psychological/physiopathology , Adult , Analysis of Variance , Biomarkers/blood , Female , Heart Rate/physiology , Humans , Hydrocortisone/blood , Lactic Acid/blood , Male , Mountaineering/physiology , New Zealand , Oxygen Consumption/physiology , Psychophysiology , Self Concept , Stress, Psychological/blood , Stress, Psychological/etiology
6.
Int J Sports Med ; 33(10): 842-5, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22592547

ABSTRACT

Venepuncture is the established "gold standard" for sampling cortisol, but it is expensive, highly invasive and impractical for many experimental and clinical settings. Salivary free cortisol is a non-invasive and practical alternative; however, when cortisol concentrations exceed 500 nmol · L there is a lack of agreement between salivary (free) and venous (bound) cortisol. No known research has assessed whether capillary cortisol accurately reflects venous blood cortisol across a range of concentrations. The objective of the current study was to determine the agreement between capillary and venous blood samples of total plasma cortisol across a range of concentrations. 11 healthy male subjects (26.1 ± 5.3 years) were recruited. Capillary and venous blood samples were collected pre and post (immediately post and post 5, 10, 15 and 20 min) a treadmill VO2max test. Regression analysis revealed a strong relationship (R2=0.96, y=1.0028x + 1.2964 (P<0.05)) between capillary and venous cortisol concentrations. A Bland-Altman plot showed all data was within the upper and lower bounds of the 95% confidence interval, and no systematic bias was evident. In conclusion, capillary sampling is a valid technique for measuring bound cortisol across a range of concentrations.


Subject(s)
Capillaries/physiology , Exercise/physiology , Hydrocortisone/blood , Veins/physiology , Adult , Humans , Male , Oxygen Consumption/physiology , Punctures , Regression Analysis , Reproducibility of Results , Saliva/chemistry , Saliva/physiology , Young Adult
7.
Spinal Cord ; 49(3): 416-20, 2011 Mar.
Article in English | MEDLINE | ID: mdl-20975731

ABSTRACT

STUDY DESIGN: Retrospective, observational study, with consecutive sampling. OBJECTIVES: To document the frequency and time frames for the achievement of independence in mobility skills for people undergoing rehabilitation following spinal cord injury (SCI). SETTING: The South Australian Spinal Cord Injury Service, Hampstead Rehabilitation Centre, Adelaide, Australia. METHODS: Retrospective data collection from a purpose-designed form. The achievement of independence in nine functional mobility skills, and time lines for this, were documented for people with a new SCI undergoing rehabilitation. Data from 152 participants were analyzed. RESULTS: Of the nine mobility-based goals evaluated, the one most likely to be achieved was sitting on the edge of the bed and the least likely was gait. Time taken to achieve the skills varied from 4 to 10 weeks on average and reflected the degree of difficulty. CONCLUSION: The frequency and time frames to achieve independence in mobility skills documented in this study will be useful when goal setting in a post-acute SCI rehabilitation setting.


Subject(s)
Gait Disorders, Neurologic/rehabilitation , Motor Skills/physiology , Paralysis/rehabilitation , Recovery of Function/physiology , Spinal Cord Injuries/rehabilitation , Adult , Aged , Female , Gait Disorders, Neurologic/etiology , Gait Disorders, Neurologic/physiopathology , Humans , Male , Middle Aged , Paralysis/etiology , Paralysis/physiopathology , Retrospective Studies , Spinal Cord Injuries/complications , Spinal Cord Injuries/physiopathology
8.
Br J Sports Med ; 45(12): 978-86, 2011 Sep.
Article in English | MEDLINE | ID: mdl-20215488

ABSTRACT

OBJECTIVE: To determine whether high-intensity, progressive gym-based exercise performed once a week is as effective as twice weekly for maintaining both subjective and objective outcomes in older adults post discharge from a metropolitan day rehabilitation centre (DRC). DESIGN: Randomised controlled trial. SETTING: Community-based exercise centre for older adults, located in Metropolitan Adelaide, South Australia. PARTICIPANTS: 21 men and 85 women who completed the DRC programme were assessed and randomly allocated to a study group. INTERVENTION: The two experimental interventions were gym-based exercise programmes (including resistance, aerobic, flexibility and balance training) varying only in frequency of delivery: either once or twice a week, directly compared with usual care (control). MAIN OUTCOME MEASURES: Lower limb strength (one-repetition maximum), balance (Berg Balance Scale), physical function (gait speed, 30-s chair stand test, timed up and go test (primary outcome) and 6-min walk test), self-reported pain (Glasgow Pain Questionnaire), activities of daily living (Barthel Index and Older Americans Resources and Services Multidimensional Functional Assessment Questionnaire), perceived benefits of and barriers to exercise (Exercise Benefits Barriers Scale), quality of life (Assessment of Quality of Life Questionnaire) and exercise frequency preference. RESULTS: Most of the outcomes (69%, 11/16) were maintained over the intervention period with no significant group effects detected between the two intervention groups or compared to the control group. Physical activity levels recorded in the control group showed a significant proportion of participants were actively exercising once weekly. A per-protocol analysis was undertaken to take this potential contamination effect into account. This showed that the control group participants, who did not exercise, did not maintain outcomes to the extent of the intervention groups, with significant group-by-time effects detected between the two intervention groups and the control group. Most of all participants (66%, 62/94) nominated once a week as their preferred exercise frequency. CONCLUSIONS: The overall finding of no significant differences between the two intervention groups for all outcomes measured gives support to the effectiveness of once-a-week exercise in maintaining outcomes at 3 months post rehabilitation. Further research is warranted given the once-a-week exercise intervention should cost less, had higher compliance and was nominated as the preferred exercise frequency by most of the participants.


Subject(s)
Exercise Therapy/methods , Exercise/physiology , Rehabilitation/methods , Activities of Daily Living , Aged , Female , Health Status , Humans , Male , Middle Aged , Muscle Strength/physiology , Muscle Stretching Exercises/methods , Muscle, Skeletal/physiology , Observer Variation , Postural Balance , Quality of Life , Resistance Training/methods , South Australia , Time Factors , Treatment Outcome
9.
Educ Health (Abingdon) ; 23(3): 393, 2010 Nov.
Article in English | MEDLINE | ID: mdl-21290358

ABSTRACT

CONTEXT: Collaborative engagement between education and health agencies has become requisite since the establishment of school inclusion policies in many developed countries. For the child with healthcare needs in an educational setting, such collaboration is assumed to be necessary to ensure a coordinated and holistic approach. However, it is less clear how this is best achieved. OBJECTIVES: This secondary research aimed to answer the questions: what are the reported models of best practice to support the collaboration between education and health staff and what are the implications for training strategies at an undergraduate and postgraduate level to affect these models? METHODS: Systematic review of current literature, with narrative summary. FINDINGS: Models of interaction and teamwork are well-described, but not necessarily well-evaluated, in the intersection between schools and health agencies. They include a spectrum from consultative to collaborative and interactive teaming. It is suggested that professionals may not be adequately skilled in, or knowledgeable about, teamwork processes or the unique roles each group can play in collaborations around the health needs of school children. DISCUSSION AND CONCLUSION: There is a need for robust primary research into the questions identified in this paper, as well as a need for educators and health professionals to receive training in interprofessional teamwork and collaboration beyond their traditional domains. It is suggested such training needs to occur at both the undergraduate and postgraduate levels.


Subject(s)
Cooperative Behavior , Faculty , Health Education , Models, Organizational , Humans
10.
Scott Med J ; 55(1): 20-3, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20218275

ABSTRACT

BACKGROUND: Defective semen quality is one of the commonest causes of infertility. The diagnosis of male fertility depends upon a descriptive evaluation of human semen, however a normal semen analysis does not necessarily indicate satisfactory fertility potential. AIMS: (i) to examine the semen quality of patients undergoing treatment by assisted conception, (ii) to explore relationships between semen quality and treatment outcomes, and (iii) to look at inter-laboratory variation in the assessment of semen quality. METHODS: Semen quality in patients undergoing assisted conception treatment between 2001 and 2004 was reviewed. Data on female age, egg numbers and fertilization outcomes was obtained by case note review. RESULTS: The thresholds used to direct patients towards IVF or ICSI treatment were comparable with the normal values promulgated by WHO, with the exception of morphology. Semen quality was not predictive of fertilization rates. When the results of independent measurements of the same sample were compared, there was diagnostic disagreement in between 10%-29% of samples. CONCLUSIONS: The conventional criteria of semen quality are used to determine treatment strategy for couples undergoing assisted conception but are not reflected in fertilization rates, emphasising the limited utility of the conventional criteria of semen quality in the assessment of sperm function. There remains significant inter-laboratory variation in the results of semen analysis.


Subject(s)
Asthenozoospermia/diagnosis , Fertilization in Vitro , Fertilization/physiology , Oligospermia/diagnosis , Semen Analysis , Adult , Asthenozoospermia/complications , Asthenozoospermia/therapy , Cohort Studies , Female , Humans , Male , Observer Variation , Oligospermia/complications , Oligospermia/therapy , Predictive Value of Tests , Reproducibility of Results , Retrospective Studies
11.
Science ; 289(5480): 762-5, 2000 Aug 04.
Article in English | MEDLINE | ID: mdl-10926535

ABSTRACT

Two different UK limestone grasslands were exposed to simulated climate change with the use of nonintrusive techniques to manipulate local climate over 5 years. Resistance to climate change, defined as the ability of a community to maintain its composition and biomass in response to environmental stress, could be explained by reference to the functional composition and successional status of the grasslands. The more fertile, early-successional grassland was much more responsive to climate change. Resistance could not be explained by the particular climates experienced by the two grasslands. Productive, disturbed landscapes created by modern human activity may prove more vulnerable to climate change than older, traditional landscapes.


Subject(s)
Biomass , Climate , Ecosystem , Plant Development , Poaceae/growth & development , Rain , Temperature , United Kingdom
13.
EClinicalMedicine ; 7: 39-46, 2019 Jan.
Article in English | MEDLINE | ID: mdl-31008449

ABSTRACT

BACKGROUND: Many women who are at increased risk of breast cancer due to a mother or sister diagnosed with breast cancer aged under 40 do not currently qualify for surveillance before 40 years of age. There are almost no available data to assess whether mammography screening aged 35-39 years would be effective in this group, in terms of detection of breast cancer at an early stage or cost effective. METHODS: A cohort screening study (FH02) with annual mammography was devised for women aged 35-39 to assess the sensitivity and screening performance and potential survival of women with identified tumours. FINDINGS: 2899 women were recruited from 12/2006-12/2015. These women underwent 12,086 annual screening mammograms and were followed for 13,365.8 years. A total of 55 breast cancers in 54 women occurred during the study period (one bilateral) with 50 cancers (49 women) (15 CIS) adherent to the screening. Eighty percent (28/35) of invasive cancers were ≤ 2 cm and 80% also lymph node negative. Invasive cancers diagnosed in FH02 were significantly smaller than the comparable (POSH-unscreened prospective) study group (45% (131/293) ≤ 2 cm in POSH vs 80% (28/35) in FH02 p < 0.0001), and were less likely to be lymph-node positive (54% (158/290, 3 unknown) in POSH vs 20% (7/35) in FH02: p = 0.0002. Projected and actual survival were also better than POSH. Overall radiation dose was not higher than in an older screened population at mean dose on study per standard sized breast of 1.5 mGy. INTERPRETATION: Mammography screening aged 35-39 years detects breast cancer at an early stage and is likely to be as effective in reducing mortality as in women at increased breast cancer risk aged 40-49 years.

14.
Hum Reprod ; 23(2): 421-6, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18084048

ABSTRACT

BACKGROUND: The role of LH in sensitizing antral follicles to FSH is unclear. LH is required for normal hormone production and normal oocyte and embryo development, but follicular responses to LH may depend upon the stage of development. Potential roles at the early follicular phase were explored in a clinical setting by employing a sequential approach to stimulation by recombinant human (r-h) LH followed by r-hFSH in women who were profoundly down-regulated by depo GnRH agonist. METHODS: We employed a multi-centre, prospective, randomized approach. Women (n = 146) were treated in a long course high-dose GnRH agonist (Decapeptyl, 4.2 mg s.c.) protocol and were randomized to receive r-hLH (Luveris, 300 IU/day) for a fixed 7 days, or no r-hLH treatment. This was followed by a standard r-hFSH stimulation regime (Gonal-F, 150 IU/day). Ultrasound and hormone assessments of responses were measured at the start of r-hLH treatment, on FSH stimulation Days 0 and 8 and at the time of HCG administration. RESULTS: The LH treatment was associated with increased small antral follicles prior to FSH stimulation (P = 0.007), and an increased yield of normally fertilized (2 PN) embryos (P = 0.03). There was no influence of the r-hLH pretreatment upon hormone profiles or ultrasound assessments during the FSH phase. Anti-mullerian hormone increased in both groups during the week prior to FSH stimulation (P = 0.002). CONCLUSIONS: This sequential approach to the use of r-hLH in standard IVF showed a possible modest clinical benefit. The results support other recent work exploring up-regulated androgen drive upon follicular metabolism indicating that clinical benefit may be obtainable after further practical explorations of the concept.


Subject(s)
Fertilization in Vitro , Follicle Stimulating Hormone, Human/pharmacology , Luteinizing Hormone/therapeutic use , Ovarian Follicle/drug effects , Ovarian Follicle/physiology , Adult , Anti-Mullerian Hormone/metabolism , Drug Administration Schedule , Embryo, Mammalian , Female , Fertilization , Humans , Luteinizing Hormone/administration & dosage , Ovarian Follicle/metabolism , Recombinant Proteins/administration & dosage , Recombinant Proteins/therapeutic use , Treatment Outcome
15.
Sex Transm Infect ; 84(1): 57-61, 2008 Feb.
Article in English | MEDLINE | ID: mdl-17911138

ABSTRACT

OBJECTIVES: To compare cervical concentrations of numerous cytokines/chemokines in women with bacterial vaginosis (BV) compared with the levels detected after BV resolution and determine if hormonal contraceptive use modulates the local inflammatory response to BV. METHODS: Cervical secretions from 81 women with BV at enrollment and normal flora at one-month follow-up were analysed for 10 different cytokines/chemokines using multiplexed fluorescent bead-based immunoassays. RESULTS: BV was associated with significantly higher concentrations of IL-1 beta, tumour necrosis factor (TNF), interferon-gamma, IL-2, IL-4, and IL-10 compared with the levels detected in the presence of normal vaginal flora. Analysis of results stratified by contraceptive practice demonstrated significantly lower levels of numerous cytokines among women with BV using hormonal contraceptives compared with those women with BV not using hormonal contraceptives. Hormonal contraceptive use was also associated with a statistically significant lesser change in TNF levels between the two study visits compared with the amount of change detected between visits among women who denied their use. CONCLUSIONS: Despite increases in the levels of both pro and anti-inflammatory cytokines in the lower genital tract of women with BV, the overall balance of these two types of molecules was maintained. The character of this local inflammatory response may help explain the typical absence of overt signs of inflammation among women with BV. In addition, hormonal contraceptive use was associated with significantly lower levels of the pro-inflammatory molecules TNF, interferon-gamma, and granulocyte macrophage colony-stimulating factor in women with BV, but did not significantly reduce the levels of IL-10, a key anti-inflammatory cytokine. These results suggest the possibility of an association between hormonal contraceptive use and altered genital tract immunity.


Subject(s)
Chemokines/metabolism , Contraceptives, Oral, Hormonal/immunology , Cytokines/metabolism , Uterine Cervicitis/immunology , Vaginosis, Bacterial/immunology , Adolescent , Adult , Cervix Uteri/chemistry , Female , Humans , Middle Aged
16.
Sci Total Environ ; 407(1): 603-14, 2008 Dec 15.
Article in English | MEDLINE | ID: mdl-18951614

ABSTRACT

Sequential extraction procedures (SEPs) are commonly used to determine speciation of trace metals in soils and sediments. However, the non-selectivity of reagents for targeted phases has remained a lingering concern. Furthermore, potentially reactive phases such as phyllosilicate clay minerals often contain trace metals in structural sites, and their reactivity has not been quantified. Accordingly, the objective of this study is to analyze the behavior of trace metal-bearing clay minerals exposed to the revised BCR 3-step plus aqua regia SEP. Mineral quantification based on stoichiometric analysis and quantitative powder X-ray diffraction (XRD) documents progressive dissolution of chlorite (CCa-2 ripidolite) and two varieties of smectite (SapCa-2 saponite and SWa-1 nontronite) during steps 1-3 of the BCR procedure. In total, 8 (+/-1) % of ripidolite, 19 (+/-1) % of saponite, and 19 (+/-3) % of nontronite (% mineral mass) dissolved during extractions assumed by many researchers to release trace metals from exchange sites, carbonates, hydroxides, sulfides and organic matter. For all three reference clays, release of Ni into solution is correlated with clay dissolution. Hydrolysis of relatively weak Mg-O bonds (362 kJ/mol) during all stages, reduction of Fe(III) during hydroxylamine hydrochloride extraction and oxidation of Fe(II) during hydrogen peroxide extraction are the main reasons for clay mineral dissolution. These findings underscore the need for precise mineral quantification when using SEPs to understand the origin/partitioning of trace metals with solid phases.


Subject(s)
Aluminum Silicates/chemistry , Chemistry Techniques, Analytical/methods , Iron/analysis , Magnesium/analysis , Chlorides/chemistry , Clay , Metals/analysis , Silicates/chemistry , Solutions , Trace Elements/analysis , X-Ray Diffraction
17.
J Clin Endocrinol Metab ; 92(1): 322-7, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17032711

ABSTRACT

CONTEXT: Ovarian surface epithelial (OSE) cells express multiple nuclear hormone receptor genes, including those encoding thyroid hormone and estrogen receptors (TR and ER, respectively). Ovarian cancer is hormone-dependent, and epidemiological evidence links hyperthyroidism, inflammation of the ovarian surface, and increased risk of ovarian cancer. OBJECTIVE: The objective of this study was to assess T3 action on human OSE cells in vitro, asking 1) is there evidence for (pre)receptor control, 2) is T3 inflammatory, and 3) does T3 affect ER expression? DESIGN: Immunohistochemical analysis of fixed human ovaries and in vitro analysis of human OSE primary cell cultures were performed. PATIENTS: Twelve women aged 29-50 yr (median, 41 yr) undergoing elective gynecological surgery for nonmalignant conditions were studied. RESULTS: Messenger RNA transcripts for TRalpha1, TRalpha2, TRbeta1, and T3 activating deiodinase 2 and inactivating deiodinase 3 were present in primary OSE cell cultures by RT-PCR. TRalpha and TRbeta proteins were also localized to intact OSE by immunohistochemistry. Treatment of OSE cell cultures for 24 h with T3 caused dose-dependent mRNA expression of inflammation-associated genes: cyclooxygenase-2, matrix metalloproteinase-9, and 11betahydroxysteroid dehydrogenase type 1, determined by quantitative RT-PCR. Finally, treatment with T3 dose dependently stimulated ERalpha mRNA expression without affecting ERbeta1 or ERbeta2. CONCLUSION: The ovarian surface is a potential T3 target. T3 exerts direct inflammatory effects on OSE cell function in vitro. OSE cell responses to T3 include increased expression of ERalpha mRNA, which encodes the ER isoform most strongly associated with ovarian cancer. This could help explain suggested epidemiological links between hyperthyroidism and ovarian cancer.


Subject(s)
Ovary/drug effects , Signal Transduction/physiology , Triiodothyronine/pharmacology , Adult , Cells, Cultured , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Female , Gene Expression Regulation/drug effects , Humans , Hyperthyroidism/complications , Iodide Peroxidase/genetics , Matrix Metalloproteinase 9/genetics , Middle Aged , Ovarian Neoplasms/etiology , Ovary/metabolism , RNA, Messenger/analysis , Receptors, Estrogen/genetics , Receptors, Thyroid Hormone/genetics
18.
Curr Biol ; 9(13): 691-4, 1999 Jul 01.
Article in English | MEDLINE | ID: mdl-10395543

ABSTRACT

Pyromorphite (Pb5(PO4)3Cl), the most stable lead mineral under a wide range of geochemical conditions [1], can form in urban and industrially contaminated soils [2] [3] [4] [5]. It has been suggested that the low solubility of this mineral could reduce the bioavailability of lead, and several studies have advocated pyromorphite formation as a remediation technique for lead-contaminated land [3] [5] [6], if necessary using addition of phosphate [6]. Many microorganisms can, however, make insoluble soil phosphate bioavailable [7] [8] [9] [10], and the solubilisation of insoluble metal phosphates by free-living and symbiotic fungi has been reported [11] [12] [13] [14] [15]. If pyromorphite can be solubilised by microbial phosphate-solubilising mechanisms, the question arises of what would happen to the released lead. We have now clearly demonstrated that pyromorphite can be solubilised by organic-acid-producing fungi, for example Aspergillus niger, and that plants grown with pyromorphite as sole phosphorus source take up both phosphorus and lead. We have also discovered the production of lead oxalate dihydrate by A. niger during pyromorphite transformation, which is the first recorded biogenic formation of this mineral. These mechanisms of lead solubilisation, or its immobilisation as a novel lead oxalate, have significant implications for metal mobility and transfer to other environmental compartments and organisms. The importance of considering microbial processes when developing remediation techniques for toxic metals in soils is therefore emphasised.


Subject(s)
Fungi/metabolism , Lead/pharmacokinetics , Aspergillus niger/metabolism , Biotransformation , Hydrogen-Ion Concentration , Oxalates/metabolism , Phosphates/metabolism , Phosphorus/metabolism , Solubility
19.
Cochrane Database Syst Rev ; (4): CD005397, 2007 Oct 17.
Article in English | MEDLINE | ID: mdl-17943853

ABSTRACT

BACKGROUND: Unilateral peripheral vestibular dysfunction (UPVD) can occur as a result of disease, trauma or post-operatively. The dysfunction is characterized by complaints of dizziness, visual or gaze disturbances and balance impairment. Current management includes medication, physical manoeuvres and exercise regimes, the latter known collectively as vestibular rehabilitation (VR). OBJECTIVES: To assess the effectiveness of vestibular rehabilitation in the adult, community dwelling population of people with symptomatic unilateral peripheral vestibular dysfunction. SEARCH STRATEGY: The search included the Cochrane Ear, Nose and Throat Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library Issue 1 2007, MEDLINE (1950 to 2007) and EMBASE (1974 to 2007). The date of the last search was March 2007. SELECTION CRITERIA: Randomised trials of adults living in the community, diagnosed with symptomatic unilateral peripheral vestibular dysfunction. Comparisons sought were: Vestibular rehabilitation versus control (placebo etc.). Vestibular rehabilitation versus other treatment (non-vestibular rehabilitation e.g. pharmacological). Vestibular rehabilitation versus another form of vestibular rehabilitation. Outcome measures that were considered included: frequency and severity of dizziness or visual disturbance; changes in balance impairment, function or quality of life; measure/s of physiological status with known functional correlation. DATA COLLECTION AND ANALYSIS: Both authors independently extracted data and assessed trials for quality. MAIN RESULTS: Thirty-two trials were identified and eleven were excluded because of mixed/unclear vestibular pathology, leaving twenty-one trials in the review. Included studies addressed the effectiveness of vestibular rehabilitation against control/sham interventions, non-vestibular rehabilitation interventions or other forms of vestibular rehabilitation, by comparing the subjects in each group who had significant resolution of symptoms and/or improved function. Individual and pooled data showed a statistically significant effect in favour of the vestibular rehabilitation over control or no intervention. The exception to this was when movement based vestibular rehabilitation was compared to physical manoeuvres for benign paroxysmal positional vertigo, where the latter was shown to be superior in cure rate in the short term. There were no reported adverse effects. AUTHORS' CONCLUSIONS: There is moderate to strong evidence that vestibular rehabilitation is a safe, effective management for unilateral peripheral vestibular dysfunction, based on a number of high quality randomised controlled trials. There is moderate evidence that vestibular rehabilitation provides a resolution of symptoms in the medium term. However there is evidence that for the specific diagnostic group of benign paroxysmal positional vertigo, physical (repositioning) manoeuvres are more effective in the short term than exercise based vestibular rehabilitation. There is insufficient evidence to discriminate between differing forms of vestibular rehabilitation.


Subject(s)
Vestibular Diseases/rehabilitation , Vestibule, Labyrinth , Dizziness/rehabilitation , Exercise Movement Techniques , Humans , Postural Balance , Randomized Controlled Trials as Topic , Sensation Disorders/rehabilitation , Vertigo/rehabilitation , Vestibular Diseases/physiopathology , Vestibule, Labyrinth/physiopathology
20.
Ultramicroscopy ; 179: 73-80, 2017 08.
Article in English | MEDLINE | ID: mdl-28433736

ABSTRACT

The simulation of (scanning) transmission electron microscopy images and diffraction patterns is most often performed using the forward-scattering approximation where the second-order derivative term in z is assumed to be small with respect to the first-order derivative term in the modified Schrödinger equation. This assumption is very good at high incident electron energies, but breaks down at low energies. In order to study the differences between first- and second-order methods, convergent beam electron diffraction patterns were simulated for silicon at the [111] zone-axis orientation at 20 keV and compared using electron intensity difference maps and integrated intensity profiles. The geometrical differences in the calculated diffraction patterns could be explained by an Ewald surface analysis. Furthermore, it was found that solutions based on the second-order derivative equation contained small amplitude oscillations that need to be resolved in order to ensure numerical integration stability. This required the use of very small integration steps resulting in significantly increased computation time compared to the first-order differential equation solution. Lastly, the efficiency of the numerical integration technique is discussed.

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