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Biomedical subjects

J Sim

Publications and source records attributed to J Sim.

At least 19 recordsLinked to original sources
PubMed2006

Glucose and diabetes: effects on podocyte and glomerular p38MAPK, heat shock protein 25, and actin cytoskeleton.

Phosphorylated p38 (pp38) mitogen-activated protein kinase (MAPK) regulates heat shock protein 25 (HSP25), stabilizing fibrillar actin (FA) and preventing cleavage to G-actin (GA). Cultured podocytes (Pods) were exposed to glucose (5.5-50 mM)+/-p38MAPK inhibitor SB202190 (SB) or control SB202474 to assess the effects on FA/GA and Pod structure. The relationship of p38MAPK with in vivo Pod structure and albuminuria (Ualb) was assessed in rats with streptozotocin (SZ)-induced diabetes (DM) for 1 week, 1 month, and 4 months. High glucose induced concentration-dependent increases in pp38MAPK and phosphorylated HSP25 (pHSP25) maintained actin cytoskeleton. Inhibition by SB diminished pp38MAPK and pHSP25, decreased FA/GA, and altered FA and GA immunohistochemical appearance. In SZ-DM, glomerular pp38MAPK and biphosphorylated HSP25 were increased after 1 week, declining at 1 month, and at or below C values at 4 months. Glomerular FA/GA in DM was normal at 1 week, declining at 1 month, and low at 4 months. Ualb/creatinine was similar in DM vs C at 1 week, and increased at 1 and 4 months. Morphometry demonstrated progressively diminishing slit pore density in DM over time, denoting evolving effacement. There were strong correlations between slit membrane density and both glomerular biphosphorylated HSP25 and ln Ualb/cr ratio. The data suggest that increased pp38MAPK and pHSP25 comprise an acute adaptation to glycemic stress. Later depletion of DM may contribute to Pod structural alterations and Ualb.

Actins↗
PubMed2006

FCMAC-Yager: a novel Yager-inference-scheme-based fuzzy CMAC.

The cerebellum is a brain region important for a number of motor and cognitive functions. It is able to generate error correction signals to drive learning and for the acquisition of memory skills. The cerebellar model articulation controller (CMAC) is a neural network inspired by the neurophysiologic theory of the cerebellum and is recognized for its localized generalization and rapid algorithmic computation capabilities. The main deficiencies in the basic CMAC structure are: (1) it is difficult to interpret the internal operations of the CMAC network and (2) the resolution (quantization) problem arising from the partitioning of the input training space. These limitations lead to the synthesis of a fuzzy quantization technique and the mapping of a fuzzy inference scheme onto the CMAC structure. The discrete incremental clustering (DIC) technique is employed to alleviate the quantization problem in the CMAC structure, resulting in the fuzzy CMAC (FCMAC) network. The Yager inference scheme (Yager), which possesses firm fuzzy logic foundation and maps closely to the logical implication operations in the classical (binary) logic framework, is subsequently mapped onto the FCMAC structure. This results in a novel fuzzy neural architecture known as thefuzzy cerebellar model articulation controller-Yager (FCMAC-Yager) system. The proposed FCMAC-Yager network exhibits learning and memory capabilities of the cerebellum through the CMAC structure while emulating the human way of reasoning through the Yager. The new FCMAC-Yager network employs a two-phase training algorithm consisting of structural learning based on the DIC technique and parameter learning using hebbian learning (associative long-term potentiation). The proposed FCMAC-Yager architecture is evaluated using an extensive suite of real-life applications such as highway traffic-trend modeling and prediction and performing as an early warning system for bank failure classification and medical diagnosis of breast cancer. The experimental results are encouraging.

Algorithms↗
PubMed2005

The relationship between hand paraesthesia and occupational factors: results from a population study.

OBJECTIVES: To investigate the association of occupational factors, both physical and psychosocial, with hand paraesthesia, and whether any such associations differ according to the concurrent presence of neck and upper limb pain (NULP). METHODS: A questionnaire was mailed to an age-stratified random sample of 9596 adults. All subjects were asked about hand paraesthesia in the past 4 weeks. Information was obtained on respondents' main job (the job held for the longest time), whether this job involved any of six neck or upper limb activities on most or all days of the working week, and questions on the psychosocial aspects of the work environment. The questionnaire also asked about NULP according to a preshaded manikin. RESULTS: A total of 5133 people replied to the survey (adjusted response 53.5%). Of these, 1592 reported abnormal feelings in the hands (prevalence of 31.9%). Prolonged gripping, prolonged bending of the neck forwards, working with arms at/above shoulder height, low job control, many changes in tasks and low job support were independently associated with hand paraesthesia. Among responders also reporting NULP, working with arms at/above shoulder height and many changes in tasks were independently associated with hand paraesthesia; prolonged gripping was linked to hand paraesthesia in the absence of NULP. CONCLUSIONS: Hand paraesthesia is associated with physical and psychosocial workplace factors, although different work-related factors were associated with hand paraesthesia according to the concurrent presence of NULP, suggesting that these symptoms may not always be mediated in the same way.

Adolescent↗
PubMed2004

Reliability and validity of measures taken during the Chester step test to predict aerobic power and to prescribe aerobic exercise.

OBJECTIVES: To evaluate the reliability and validity of measures taken during the Chester step test (CST) used to predict VO(2)max and prescribe subsequent exercise. METHODS: The CST was performed twice on separate days by 7 males and 6 females aged 22.4 (SD 4.6) years. Heart rate (HR), ratings of perceived exertion (RPE), and oxygen uptake (VO(2)) were measured at each stage of the CST. RESULTS: RPE, HR, and actual VO(2) were the same at each stage for both trials but each of these measures was significantly different between CST stages (p<0.0005). Intertrial bias +/-95% limits of agreement (95% LoA) of HR reached acceptable limits at CST stage IV (-2+/-10 beats/min) and for RPE at stages III (0.2+/-1.4) and IV (0.5+/-1.9). Age estimated HRmax significantly overestimated actual HRmax of 5 beats/min (p = 0.016) and the 95% LoA showed that this error could range from an underestimation of 17 beats/min to an overestimation of 7 beats/min. Estimated versus actual VO(2) at each CST stage during both trials showed errors ranging between 11% and 19%. Trial 1 underestimated actual VO(2)max by 2.8 ml/kg/min (p = 0.006) and trial 2 by 1.6 ml/kg/min (not significant). The intertrial agreement in predicted VO(2)max was relatively narrow with a bias +/-95% LoA of -0.8+/-3.7 ml/kg/min. The RPE and %HRmax (actual) correlation improved with a second trial. At all CST stages in trial 2 RPE:%HRmax coefficients were significant with the highest correlations at CST stages III (r = 0.78) and IV (r = 0.84). CONCLUSION: CST VO(2)max prediction validity is questioned but the CST is reliable on a test-retest basis. VO(2)max prediction error is due more to VO(2) estimation error at each CST stage compared with error in age estimated HRmax. The HR/RPE relation at >50% VO(2)max reliably represents the recommended intensity for developing cardiorespiratory fitness, but only when a practice trial of the CST is first performed.

Adult↗
PubMed2003

Nondestructive evaluation of explosively welded clad rods by resonance acoustic spectroscopy.

A resonance acoustic spectroscopy technique is assessed for nondestructive evaluation of explosively welded clad rods. Each rod is modeled as a two-layered cylinder with a spring-mass system to represent a thin interfacial layer containing the weld. A range of interfacial profiles is generated in a set of experimental samples by varying the speed of the explosion that drives the copper cladding into the aluminum core. Excellent agreement is achieved between measured and calculated values of the resonant frequencies of the system, through appropriate adjustment of the interfacial mass and spring constants used in the wave scattering calculations. Destructive analysis of the interface in the experimental specimens confirms that key features of the interfacial profile may be inferred from resonance acoustic spectroscopy analysis applied to ultrasonic measurements.

Acoustics↗
PubMed2003

Intention-to-treat approach to data from randomized controlled trials: a sensitivity analysis.

The intention-to-treat (ITT) approach to randomized controlled trials analyzes data on the basis of treatment assignment, not treatment receipt. Alternative approaches make comparisons according to the treatment received at the end of the trial (as-treated analysis) or using only subjects who did not deviate from the assigned treatment (adherers-only analysis). Using a sensitivity analysis on data for a hypothetical trial, we compare these different analytical approaches in the context of two common protocol deviations: loss to follow-up and switching across treatments. In each case, two rates of deviation are considered: 10% and 30%. The analysis shows that biased estimates of effect may occur when deviation is nonrandom, when a large percentage of participants switch treatments or are lost to follow-up, and when the method of estimating missing values accounts inadequately for the process causing loss to follow-up. In general, ITT analysis attenuates between-group effects. Trialists should use sensitivity analyses on their data and should compare the characteristics of participants who do and those who do not deviate from the trial protocol. The ITT approach is not a remedy for unsound design, and imputation of missing values is not a substitute for complete, good quality data.

Data Interpretation, Statistical↗
PubMed2002

Series of incidents of Listeria monocytogenes non-invasive febrile gastroenteritis involving ready-to-eat meats.

AIMS: A series of cases and outbreaks of febrile noninvasive gastrointestinal disease involving 31 identified cases was investigated in terms of the numbers and types of Listeria monocytogenes present in the suspect foods (ready-to-eat meats) and clinical samples from cases. METHODS AND RESULTS: Foods and faecal samples involved in the incidents were tested for the presence and number of L. monocytogenes. Isolates were typed by macrorestriction analysis using pulsed-field gel electrophoresis. The foods contained high levels of L. monocytogenes, in one case 1.8 x 10(7) g-1. Faecal samples contained L. monocytogenes for up to 15 d after the contaminated food was consumed. All isolates from the food and faecal samples were of serotype 1/2 and were indistinguishable from one another by macrorestriction typing. CONCLUSIONS: It is likely that the meats were contaminated either during their manufacture after they had been cooked or by underprocessing. The long shelf lives on these products would have allowed the contaminating L. monocytogenes to grow to the high numbers measured in this study, causing food poisoning as described. SIGNIFICANCE AND IMPACT OF THE STUDY: Outbreaks of febrile noninvasive listeriosis are relatively rare. This report adds ready-to-eat meats to the range of foods that have acted as vehicles for such outbreaks.

Bacterial Typing Techniques↗
PubMed2002

Viral hepatitis in South African healthcare workers at increased risk of occupational exposure to blood-borne viruses.

The prevalence of hepatitis A, B and C antibodies was measured in a group of healthcare workers (HCWs) at increased risk of occupational acquisition of blood-borne viruses (N=402) from a large, urban referral hospital in South Africa. The aims of this study were to determine the immunity of HCWs to these agents and to recommend policy for the protection of HCWs against occupational exposure to viral hepatitis in this country. Race, sex and age were shown to be important factors influencing the presence of hepatitis A (HAV) antibodies. Most black HCWs (96.2%) are protected from HAV infection. Females have significantly higher HAV antibodies compared with males and antibodies increase with increasing age. Hepatitis B antibodies (anti-HBs) were found in 30.6% of HCWs. Anti-HBs levels were significantly associated with a past history of HBV vaccination. However, only a small proportion of HCWs (21.2%) could remember ever being immunized against HBV. For those individuals that did receive HBV vaccination (N=83), the mean number of years since their last vaccine was 6.2 years (SD +/- 3.5). HCV antibodies were found in 1.8% of HCWs at increased risk of occupational exposure. It was not possible to define whether these infections were occupationally acquired but genotyping of the HCV (in two of seven cases) showed genotype 5, the predominant South African genotype. New recommendations for the prevention of viral hepatitis in HCWs in South Africa are made, including pre-employment screening for HAV based on self-selection criteria, universal anti-HBs screening with HBV booster vaccination. HCV recommendations are based on appropriate education of HCWs about this infection and its prevention and a standardized post-exposure testing protocol.

Adult↗
PubMed2001

Mutation of N304 to leucine in Streptomyces clavuligerus deacetoxycephalosporin C synthase creates an enzyme with increased penicillin analogue conversion.

Superimposition of deacetoxycephalosporin C synthase (DAOCS) and isopenicillin N synthase (IPNS) structures revealed that R74, R160, R266 and N304 are strategically located in the catalytic cavity of Streptomyces clavuligerus DAOCS (scDAOCS) and are crucial for orchestrating different substrates. Substitutions at these sites to a hydrophobic leucine residue were expected to stabilize the hydrophobic substrate bound state. Substantial improvements in the biotransformation of penicillin G, ampicillin and amoxicillin to their respective cephalosporin moieties were observed using the N304L mutant scDAOCS. Thus, our results have demonstrated the enhancement of scDAOCS activity via critical computational analysis and site-directed mutagenesis of endogenous ligands.

Amino Acid Substitution↗
PubMed2001

The effect of introduction of universal childhood hepatitis B immunization in South Africa on the prevalence of serologically negative hepatitis B virus infection and the selection of immune escape variants.

The effect of universal hepatitis B vaccination on the prevalence of serologically negative hepatitis B virus infection (HBV) and the emergence of HBsAg variants is unknown. We prospectively studied two different cohorts of 12--24 month old children in South Africa. They consisted of the unvaccinated children (n=459) born before the introduction of universal vaccination and the vaccinated children (n=1213) between 1 and 2 years after the introduction of the vaccination program. The frequency of detecting HBV DNA by PCR was reduced from 6.5% in unvaccinated children to 0.3% in vaccinated children (P<0.00001). There were no unique amino acid substitutions within the major hydrophilic region of the S sequence in both pre- and post-vaccination samples. Universal childhood vaccination reduced the frequency of serologically negative HBV infection and did not necessarily lead to selection of escape variants.

Amino Acid Sequence↗
PubMed2001

The invariant F283 and its strategic position in the hydrophobic cleft of Streptomyces jumonjinensis isopenicillin N synthase active site are functionally important.

Isopenicillin N synthase (IPNS) and related non-haem iron-binding enzymes including deacetoxycephalosporin C synthase (DAOCS) are proposed to have structurally similar active centers. Sequence alignment and computational structural analyses of predicted structures revealed 11 highly conserved hydrophobic amino acid residues in 134 IPNS-related enzymes form a contiguous hydrophobic patch in the IPNS active center, wherein F283 is strategically positioned. The investigation of single and double mutations at F283, adjacent (L284) and proximal sites (N285 and S216) of Streptomyces jumonjinensis IPNS advocate the explicit importance of the phenyl ring at position 283. A similarly placed phenylalanine (F264) in DAOCS was found to be also crucial for its enzyme activity.

Amino Acid Sequence↗
PubMed2001

Differential assembly of rat purinergic P2X7 receptor in immune cells of the brain and periphery.

ATP-gated P2X(7) purinoceptors are found in most immune cells of the periphery and the brain where their activation leads to multiple downstream events such as cell permeabilization, apoptosis, and/or cytokine release. P2X(7) receptors do not form heteromeric receptors with any of the other six P2X subunits, and it is not known what type of homomeric assemblies the P2X(7) subunit makes. We constructed and purified an ectodomain protein of the rat P2X(7) receptor (amino acids 60-323) and used this to generate a monoclonal antibody (Ab) with which to probe P2X(7) receptors in central and peripheral immune cells. In HEK cells expressing rat P2X(7) receptors, the Ab increased the maximum current evoked by BzATP by 3-8-fold with a 5-fold leftward shift in EC(50) concentration. This Ab recognized only a non-denatured, multimeric form of the receptor on blue native-PAGE but did not recognize the denatured form on SDS-PAGE. A C-terminal polyclonal P2X(7) Ab recognized both monomeric subunits on SDS-PAGE and a multimeric complex on blue native-PAGE in this heterologous expression system. With Western blotting using these two Abs, native P2X(7) receptors in peritoneal macrophage and bone marrow cells are shown to exist as a strongly bound multimeric complex, whereas P2X(7) receptors in brain glia and/or astrocytes appear to form only as monomeric subunits.

Animals↗
PubMed2001

Inhaled corticosteroids decrease vascularity of the bronchial mucosa in patients with asthma.

BACKGROUND: Increased vascularity in airway mucosa is a distinctive feature of airway remodelling in asthma. While corticosteroids have proved most effective in modifying airway inflammation, the effect of inhaled corticosteroids on increased airway mucosal vascularity in asthmatics has been little studied. OBJECTIVE: We examined the effect of inhaled corticosteroid on airway vascularity in bronchial biopsy specimens taken from asthmatic patients. SUBJECTS AND METHODS: We studied bronchial biopsies from 28 asthmatic patients before and after treatment with inhaled beclomethasone dipropionate (BDP) 800 microg/daily, or placebo, for 6 months in a double-blind manner. Biopsy specimens were evaluated for number of vessels and percentage of area occupied by vessels, using computerized image analysis after staining for type IV collagen in vessel walls. Specimens were also examined for extent of collagen III in the subepithelial basement membrane. In addition, we compared asthmatic specimens with biopsy specimens taken from non-asthmatic control subjects. RESULTS: There was a significant increase in number of vessels (P < 0.01) and percent vascularity (P < 0.001) in the submucosa of asthmatic patients compared with control subjects. After 6 months of treatment, we observed significant improvements in forced expiratory volume in 1 s (FEV1), FEV1% and airway responsiveness (P < 0.05, each) in the BDP treatment group compared with the placebo group. This was accompanied by significant decreases in both vessel number and percent vascularity in the airways of BDP-treated patients (P < 0.05, each). We also observed a significant correlation between change in percent vascularity and change in collagen III thickness in the BDP-treated patients (rs = 0.90, P < 0.001). Furthermore, the change in percent vascularity was inversely correlated with both FEV1 (rs = -0.49, P < 0.05) and airway responsiveness (rs = -0.36, P < 0.05). CONCLUSION: These findings suggest that inhaled corticosteroid treatment of asthma reduced airway wall vascularity during airway remodelling.

Adolescent↗
PubMed2001

Nurses' perceptions of physiotherapists as rehabilitation team members.

OBJECTIVE: To investigate nurses' perceptions of physiotherapists as members of the rehabilitation team. This study arose from the current emphasis that is placed on good multidisciplinary teamwork for effective rehabilitation and the awareness that different team members often have different perceptions of their respective roles within the team. DESIGN: Semi-structured interviews, the results of which were then subject to content analysis. SETTING AND SUBJECTS: Experienced rehabilitation nurses in two rehabilitation wards within a National Health Service Trust. RESULTS: Nurses perceived the role of physiotherapists as being concerned with mobility and movement, and valued the therapists' knowledge and skills in these areas. They felt, however, that physiotherapists had insufficient understanding of the demands and pressures of nursing practice and lacked recognition of the nurses' professional autonomy in decision-making in rehabilitation. Nurses viewed nursing and physiotherapy as two quite distinct and different roles within rehabilitation, despite some role overlap. Physiotherapy was perceived as specific and measurable, while nursing was perceived as generalized and undefined. These perceptions extended to their views on patient-staff interactions and organizational structures. Some of the differences, such as organizational structures, created barriers to rehabilitation. Others, such as physiotherapy expertise in mobility, were valued for their contribution to rehabilitation. Areas were identified where the two professions can assist each other in professional skills. CONCLUSION: Nurses valued the role and contribution of physiotherapists, but identified areas in which barriers existed to effective interprofessional working, particularly in relation to organizational factors and interprofessional relationships.

Adult↗
PubMed2000

'You'll never walk alone': CCTV surveillance, order and neo-liberal rule in Liverpool city centre.

This paper is concerned to chart the establishment and uses of CCTV within the location of Liverpool city centre. In doing this the paper seeks to contextualize CCTV within contemporary 'partnership' approaches to regeneration which are reshaping the material and discursive form of the city. Thus CCTV schemes along with other security initiatives are understood as social ordering strategies emanating from within locally powerful networks which are seeking to define and enact orderly regeneration projects. In focusing on the normative aspects of CCTV, the paper raises questions concerning the efficacy of understanding contemporary forms of 'social ordering practices' primarily in terms of technical rationalities while neglecting other, more material and ideological processes involved in the construction of social order.

Authoritarianism↗
PubMed2000

Ratings of perceived exertion in braille: validity and reliability in production mode.

OBJECTIVES: (a) To assess the validity and reliability of producing and reproducing a given exercise intensity during cycle ergometry using a braille version of Borg's standard 6-20 rating of perceived exertion (RPE) scale, and (b) to determine whether the exercise responses of blind participants, at a given produced RPE, were similar to those reported in recognised guidelines for sighted subjects. METHODS: Ten healthy registered blind volunteer participants (four women, six men; mean (SD) age 23.2 (9.0) years) performed an initial graded exercise cycle test to determine maximal heart rate (HRMAx) and maximal oxygen uptake (VO2MAX). Three trials of three exercise bouts at RPEs 9, 11, and 13 were then performed in random order on three separate days of the same week, with expired air and heart rate measured continuously. Each exercise bout was followed by 10 minutes of rest. The validity of the scale as a means of producing different exercise intensities was assessed using a two factor (RPE x trial) repeated measures analysis of variance. Intertrial reliability was assessed using intraclass correlation coefficients (ICC) and the bias +/-95% limits of agreement (95%LoA) procedure. RESULTS: Participants reported no difficulty in using the braille RPE scale. When asked to produce exercise intensities equating to RPE 9, 11, and 13, they elicited mean %VO2MAX values of 47%, 53%, and 63% respectively. Analysis of variance showed no significant differences in either %HRMAx or %VO2MAX between trials at each of the three RPEs, but there was a significant difference (p<0.001) in both %HRMAx and %VO2MAX between the three RPE levels. All pairwise comparisons of the three different RPEs were significantly different (p<0.016). The ICC between the second and third trial for %HRMAx was significant (p <0.05) for all three RPEs. Similarly for %VO2MAX, the ICC was significant for RPE 9 and 11 but not 13. The 95%LoA decreased for both %HRMAx and %VO2MAX with each successive trial. CONCLUSIONS: Blind participants were successful in using a braille RPE scale to differentiate exercise intensity on a cycle ergometer. In every trial at RPE 13, all participants achieved %HRMAX and %VO2MAX levels, which fell within the recommendedrange for developing cardiorespiratory fitness. Using %HRMAx as a judge of intertrial reliability, the participants were able to repeat similar exercise intensities after two trials at each of the three RPEs (9, 11,13). The same was true for RPE 9 and 11, when %VO2MAX was used as a judge, but further trials were required to achieve similar reliability at RPE 13. A braille RPE scale can be used by healthy blind people during cycle ergometry, with similar effect to the visual analogue scale recommended for use in healthy sighted people.

Adult↗
PubMed2000

Confidentiality within physiotherapy: perceptions and attitudes of clinical practitioners.

OBJECTIVES: This study examined the issue of confidentiality in relation to i) undergraduate curriculum content in physiotherapy, and ii) the awareness, experiences and attitudes of clinical physiotherapists. DESIGN: Postal survey of universities and focus group interviews with physiotherapists. SETTING: Twenty-five universities in the UK and Ireland and 44 therapists in five hospitals in southern England. RESULTS: The survey of universities indicated that legal and ethical aspects of confidentiality featured in virtually all preregistration courses that responded. However, whereas its inclusion was rated as extremely important, the degree of coverage of confidentiality varied considerably between courses. Within the focus groups, 35 informants recollected coverage of confidentiality in their preregistration education, and 12 in postregistration in-service training; in neither case was this coverage in great detail. Informants identified environmental factors and working practices as barriers to preserving confidentiality. Disclosure to others also gave rise to difficulties. Informants were only aware in general terms of the relevant sections of the Chartered Society of Physiotherapy's Rules of Professional Conduct. CONCLUSIONS: Aspects of hospital-based physiotherapy practice were seen to create specific problems in relation to confidentiality. More detailed sources of education and guidance on this issue appear to be required.

Adult↗