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CLINICALLY RELEVANT EX VIVO FATTY ACID PROFILES FROM A LIPID MODEL FOR COLORECTAL ADENOCARCINOMANel, Amanda 23 October 2009 (has links)
The challenge we face today is identification of the mechanisms
through which dietary factors perturb fundamental fatty acid (FA) pathways in cancer cells.
In principle, insight into a lipid model for the cancer entity under assessment is required.
This prompted and investigation into FA role-players that drive cellular over-production
and apoptotic pathways under circumstances where environmental factors impede
essential fatty acid metabolism (EFAM) that contributes to colorectal cancer (CRC).
Ultimately, better understanding of FA metabolic pathways followed under colorectal
pathological conditions can contribute to improved therapies by which growth and
recurrence of this disease may be obviated. PURPOSE OF STUDY: The primary goal of
this study was to construct clinically relevant ex vivo FA profiles from a lipid model for
colorectal adenocarcinoma, not previously reported in the literature. Aims were to identify
prominent FA role-players and to debate their involvement in different signaling pathways.
The final purpose of this study was to present a rationale for adjuvant FA therapies to
improve the management of CRC. MATERIAL AND METHODS: The study group
consisted of CRC biopsies (TNM staging, mostly T2/T3) and normal colorectal mucosal
biopsies, (n8 of each group). Biopsy selection was hampered by difficult circumstances,
since most patients received treatment prior to surgery. All the lipid analyses were
personally conducted at the Biolipid Division of the Department Biochemistry at the
University of the Free State (UFS) as follows: lipids were extracted; total lipids (TLs) were
fractionated into neutral lipids (NLs) and phospholipids (PLs); phosholipid subclasses, i.e.
phosphatidylcholine, (PC), phosphatidylserine (PS), phosphatidylethanolamine (PE) and
phosphatidylinositol (PI), were separated; and fatty acid methyl esters of all the classes
and subclasses were analyzed. Lipid analyses were done according to well established
and internationally accepted gaschromatography (GLC) and thin layer chromatography
(TLC) techniques. Statistical analyses were performed by a biostatistician attached to the
UFS, and p-values and 95% confident intervals (95% CI) for median of differences, as
well as specific ratios were calculated. MAIN RESULTS AND DISCUSSION: The ex vivo
phospholipid FA profile for CRC cells revealed linoleic acid (LA), arachidonic acid (AA),
palmitic acid (PA) and oleic acid (OA) as main role-players involved in CRC. An extensive
literature study revealed that: prolonged inflammatory responses and oxidative events,
marked by the up-regulation of cyclooxygenases (COXs) and inducible nitric oxide
synthase (iNOS), contribute to colorectal carcinogenesis; and prolonged cytokine mediated responses, orchestrated by nuclear factor-kappa Beta (NF-κβ) with consequent
immunodeficiency, are prevalent in CRC patients. Past research revealed without doubt
that high dietary AA intake (meat) and COX-2 metabolism play a pivotal role during
colorectal carcinogenesis. CRC is a stress-related cancer and it is plausible that high iron
intake and lipids contribute to chronic inflammation and radical-mediated cell damage in
this age-related disease. Current research directions in CRC concern LOX metabolism
and peroxisome proliferator activator receptors (PPARs) are receiving much attention,
especially PPARδ/β that was an enigma and elicited controversial debate in adenomas
(polyps) and adenocarcinoma. Taken together at this point in time, the impact of
environmental factors on essential fatty acid metabolism (EFAM) that impede LA
conversion to AA via delta-6 and -5 desaturase (Î6d and Î5d) pathways with up-regulation
of the fatty acid synthase (FAS) and Î9d pathways, and the down-regulation of LA
oxidative metabolism via the 15 LOX-1 pathway with up-regulation of the COX-2 and 15-
LOX-2 pathways of AA, is characteristic of colorectal carcinogenesis. Seen in context, the
lipid findings of this study integrated with evidence-based information in the literature
encompasses the following: excessive dietary linoleic acid (LA) intake that can contribute
to cell proliferation, radical-mediated cell damage, and the production of conjugated
linoleic acid (CLA) in the gut; high dietary AA intake and COX-2 over-expression that play
a pivotal role during carcinogenesis and immune responses with consequent exhaustion
of the AA source; enhanced FAS and Î9d activities that contribute to, respectively,
enhanced palmitic acid (PA) and oleic acid (OA), is prevalent in CRC cells. The high PA
content in CRC cells apparently activates PPARδ/β and thereby suppresses apoptosis, a
crucial factor in the pathobiology of CRC. The link between OA and CRC still needs
proper clarification. It is conceivable that the high saturated fatty acid (SFA) content
observed in CRC cells, exogenous intake with red meat and endogenous production by
enhanced FAS activity, contribute to colorectal carcinogenesis and immunodeficiency in
CRC patients, since it can stimulate COX-2 expression (and PGE2 activity) and downregulate
the Th1 immune pathway that make CRC a Th2 dominant disease. Taken in
consideration that lipid rafts rich in SFAs down-regulate the Th1 cytokine subset,
particularly interleukin-2 (IL-2) that stimulates lymphocyte production, it is plausible that
management of the CRC patient is hampered by immunodeficiency. All the altered cell
signaling pathways in CRC debated in this study served as sound foundation for clinical
intervention with adjuvant FA therapeutic strategies to improve CRC management.
CONCLUSION: The identification of prominent FA role-players in CRC cells that serve as
ligands for specific PPAR family members contributed to the assessment of FA driven
proliferation and apoptotic pathways characteristic of CRC. It is conceivable that enhanced PA (and LA) contributes to PPARδ/β over-expression that can suppress PPARγ
(and PPARα) activity and then tilts the scale in favor of apoptotic resistance and survival
of CRC cells. From an epidemiological viewpoint, excessive iron and SFAs seem to be
important co-factors in the multifactorial etiology of CRC. The biohydroxygenation of LA
to different CLA products in the gut and to what extent harmful CLA products may pose a
danger need to be fully explored, especially since the uptake of beneficial products is
apparently limited. Among current therapeutic options in the field of lipids, concurrent
therapy with a COX-2 inhibitor (Celecoxib) and docosahexaenoic acid (DHA) to improve
membrane fluidity and the impact of drug therapy entered clinical trials and although the
outcome is still awaited, the impact of DHA on lymphocyte production may be a concern.
Based on a mountain of evidence presented in this study, it is suffice to say that there is a
rationale for additional adjuvant FA therapies that can be included in the existing
therapeutic regime for CRC management. Firstly, CLA and EPA therapy for prevention of
polyp recurrence and improvement of immunocompetence in CRC patients and secondly,
GLA and EPA therapy in the management of patients with a history of polyp growths is
proposed.
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THE EVALUATION OF STRATEGIES FOR PRODUCING OPTIMAL INHALANT THERAPY IN PRESCHOOL CHILDREN (2-6 YEARS) WITH CHRONIC ASTHMASchultz, André 15 December 2010 (has links)
Background:
The dose of inhaled medication reaching a patient is dependent on drug formulation,
method of delivery, output and correct use of the delivery device and frequency of use.
The most commonly used aerosol drug delivery device in preschool children is the
pressurised metered-dose inhaler (pMDI) -spacer. This study evaluated strategies for
improving the delivery of inhalation therapy in preschool children by focusing on factors
affecting the optimal use of pMDI-spacers and on the frequency of their use as determined
by adherence to prescribed drug regimes.
The study was divided into two parts. Part 1 examined the number and type of breaths
needed for efficient drug delivery through a pMDI-spacer in preschool children. Part 2 was
a randomised, controlled, prospective clinical trial in which a comparison was made
between an incentive spacer device and a small volume spacer with respect to adherence,
correct device use (spacer technique) and clinical outcome.
Overall aims:
⢠To determine how many tidal breaths are required to effectively inhale medication
from different types of spacer/ valved holding chamber devices, and to determine the
efficacy of a single maximal inhalation for drug delivery in young children.
⢠To investigate the relationship between factors that determine dose delivery of
inhaled asthma maintenance therapy and symptom control in preschool asthmatic children.
⢠To determine the influence of an incentive inhalation delivery device on drug
delivery and clinical outcome in preschool asthmatic children. Part One (Chapters Two and Three):
Background: The pMDI-spacer combination is currently the most commonly used method
of drug delivery to preschool asthmatics. A patientâs competence in using a pMDI-spacer
is an important part of drug delivery. Preschool children are instructed to breathe normally
(tidally) through spacer devices. There is little evidence on the number of breaths required
for optimal drug delivery. Whether the single maximal breath technique has a place in
spacer use in preschool children also remains unclear. Due to a lack of data, authors of
asthma guidelines have been unable to give evidence-based instruction on how a preschool
child should breathe through a spacer.
Aims: To determine the optimal method of breathing through a spacer for preschool
asthmatic children to ensure effective drug delivery.
Hypothesis: Based on technical data on in vitro spacer performance and knowledge of tidal
flow patterns in young children the hypothesis is that a limited number of breaths would be
sufficient for efficient drug inhalation via spacer in preschool children.
Methods: A method for reliably recording and simulating breathing of patients using
pMDI-spacer devices was designed, constructed and validated. Breathing flow patterns
were recorded in preschool children inhaling placebo from spacers. The breathing patterns
were reproduced by a breathing simulator which was connected to spacer devices.
Breathing patterns previously recorded using each specific type of spacer, were simulated
with the corresponding spacer type. To estimate delivery, the mass of salbutamol was
measured on a filter interposed between the spacer and the simulator. Four different spacer
devices, the Aerochamber Plus®, Funhaler®, Volumatic® and a modified 500ml plastic
soft drink bottle were tested with a salbutamol pMDI. The effect of different numbers of
tidal breaths and that of a single maximal breath on drug delivery were compared.
Results: Drug delivery via the Funhaler® mean (95CI) was 39% (34-43) and 38% (35-42)
of total dose recovered from filter, pMDI and spacer, for two and nine tidal breaths
respectively. Drug delivery via the Aerochamber Plus mean (95CI) was 40% (34-46) and
41% (36-47) for two and nine tidal breaths respectively. There was no significant difference in drug delivery after three tidal breaths mean (95CI) 40% (36-44%) and nine
tidal breaths nine tidal breaths; mean (95CI) 37% (33-41) for the Volumatic®. With the
(unvalved) modified soft drink bottle, there was no significant difference in drug delivery
between two, five or nine tidal breaths.
Inhalation volumes were almost double the expected tidal volumes. The inhalation volume
means (SD) of subjects using the Aerochamber Plus®, the Funhaler®, the Volumatic® and
the modified soft drink bottle were respectively 393ml (247), 432ml (225), 384ml (185),
445ml (167) during tidal breathing and 515ml (164), 550ml (239), 503ml (213), 448ml
(259) for the single maximal breath manoeuvre.
100% of seven year old children, 84% of six year olds, 76% of five year olds, 38% of four
year olds and 20% of three year olds could perform a single maximal breath manoeuvre.
Nine tidal breaths resulted in significantly greater drug delivery to filter than single
maximal inhalation for both the Funhaler® (p=0.04) and the Volumatic® (p=0.01). There
was no significant difference in drug delivery to filter between single maximal inhalation
and nine tidal breaths with both the Aerochamber Plus® and the modified soft drink bottle.
Conclusion: In preschool children, two tidal breaths were adequate for drug delivery
through small volume valved spacers and a 500ml modified soft drink bottle. For a large
volume spacer, three tidal breaths were adequate for drug delivery.
Part Two (Chapters Four and Five):
Background: Drug delivery by pMDI-spacer is determined by many different factors,
including spacer technique and adherence to prescribed medication. The effect of both
spacer technique and adherence on clinical outcome has been demonstrated in older
asthmatics. In this part of the thesis the influence of these factors on clinical outcome in
preschool asthmatics was firstly investigated. Thereafter, the additional influence of an
incentive spacer device on adherence, spacer technique and clinical outcome was also
assessed.
Aims:
⢠To investigate the effect of proficiency in spacer technique, as measured by
deposition of drug inhaled onto a filter, on clinical outcome in preschool asthmatic
children.
⢠To investigate the effect of adherence to prescribed inhaled asthma medication on
clinical outcome in preschool asthmatic children.
⢠To investigate the influence of the use of an incentive spacer device on inhaled drug
dose, adherence to prescribed treatment and clinical outcome in preschool asthmatic
children.
Hypothesis:
⢠Proficiency in spacer technique correlates positively with improved clinical
outcome.
⢠Good adherence to prescribed medication regimens correlates positively with
improved clinical outcome.
⢠Use of an incentive spacer device, the Funhaler® , improves both competency in
spacer technique and adherence to prescribed medication and thereby improves clinical
outcome in preschool children with asthma. Methods: A prospective randomised, controlled clinical trial was performed. Subjects
were two to six year old children who had doctor-diagnosed asthma and were on daily
maintenance therapy with inhaled corticosteroids. Maintenance therapy was delivered by
Funhaler® in the study group and Aerochamber Plus® in the control group. Subjects were
assessed for the following outcomes at three-monthly intervals for one year:
(1) Proficiency in spacer technique was measured at each study visit by measuring the
drug dose deposited on a filter interposed between the subject and the spacer.
(2) Adherence was monitored using an electronic monitoring device (Smartinhaler)
(3) Asthma symptoms were monitored using diary cards.
(4) Quality of life (QoL) was measured using the PedsQL questionnaires.
(5) Lung function was monitored using the forced oscillation technique.
The Funhaler group was then compared with the Aerochamber Plus group in terms of
determinants of drug delivery and markers of clinical outcome.
Results: One hundred and thirty two subjects were included in the study. One hundred and
eleven patients (84%) completed the study. By the six month follow-up, significantly more
subjects in the Funhaler group had dropped out of the study (p=0.04).
Throughout the clinical trial, there was large intra-subject variation in proficiency in spacer
technique, as measured by drug dose deposited on filter. Individual patient drug doses
recovered from the filters ranged from zero to 136μg (calculated as the mean of five 100μg
pMDI actuations). There was no significant correlation between proficiency in using the
delivery device and any measure of asthma control (p > 0.05). Correcting for age, gender,
and adherence to prescribed medication did not influence the results.
Inter subject variability in adherence to prescribed medication was extremely high
throughout the study. Adherence to prescribed medication ranged from 1% to 99%. There
was a significant correlation between adherence to prescribed medication and nights
without wheeze, throughout the study period (r = 0.01; p = 0.01). The correlation between
adherence to prescribed medication and nights without wheeze remained after correcting
for age, gender, proficiency in spacer technique, and the number of nights without wheeze
at the baseline visit (r = 0.01; p = <.01). There was also a significant correlation between
adherence to prescribed treatment and (daytime) days without wheeze (r = 0.01; p = 0.01).
The correlation ceased to be significant after correcting for age, gender, proficiency in spacer technique, and (daytime) days without wheeze at the time of the baseline visit.
There was a significant correlation between adherence to prescribed medication and
bronchodilator free days (r = 0.01; p = 0.02) throughout the study. After correcting for age,
gender, proficiency in spacer technique, and bronchodilator free days at baseline, the
correlation between adherence to prescribed medication and bronchodilator free days
remained significant (r = 0.01; p = 0.01). There was no significant correlation between
adherence and other markers of clinical outcome.
After correcting for age and gender, the Funhaler group demonstrated significantly higher
proficiency in spacer technique as determined by filter dose (p = 0.05). The improved
proficiency in spacer technique in the Funhaler group was limited to subjects who were
younger than 4 years of age at the baseline visit (p < 0.01).
There was no significant difference in adherence to prescribed medication between the
Funhaler group and the Aerochamber Plus group (p = 0.93). Correcting for age and gender
did not influence the results.
At the start of the clinical trial (baseline visit), the Funhaler group reported significantly
less days without wheeze (p = 0.03), and significantly less bronchodilator free days (p =
0.02) than the Aerochamber Plus group in the seven days before the baseline visit. The
Funhaler group also scored lower than the Aerochamber group in terms of QoL scores at
the time of randomisation (p = 0.05). Where needed, various measures were used to correct
for the significant differences at baseline, between the Funhaler group and the
Aerochamber Plus group. There was no significant difference between the Funhaler group
and the Aerochamber Plus group in terms any of clinical outcome measures used.
Correcting for age, gender did not influence the results.
Discussion: Use of the Funhaler® therefore appeared to specifically improve drug delivery
in those subjects who, with a conventional spacer, would have inhaled very low doses of
medication. The Funhaler® was therefore partially successful as an incentive device, as its
use positively influenced drug delivery in a specific sub-group of preschool children.
Proficiency in spacer technique did not translate to improved clinical outcomes. Various
reasons for the lack of association between proficiency in spacer technique and clinical outcome, including the inevitable inherent limitations in design in a clinical study, are
discussed.
Results suggest that adherence to prescribed medication regimens correlates positively with
improved clinical outcome in preschool children with asthma. Use of the Funhaler® did
not improve adherence to prescribed medication, or clinical outcome, in preschool children
with asthma. Funhaler® therefore failed as an incentive device to improve long term
adherence, and clinical outcome, in preschool asthmatic children. Future design for an
incentive device will need to consider providing feedback that is of more ongoing interest
to the child.
As the large variation, as observed in this study, in proficiency in spacer technique, and
adherence to prescribed medication, is likely to influence results of clinical trials, an
awareness of the variation in spacer technique and drug delivery may contribute towards
the accurate interpretation of results in future studies.
Finally, the wide variation in both proficiency in spacer technique, and adherence to
prescribed medication, both factors that determine drug delivery to patients, highlight the
importance of pursuing ways to improve inhalation drug delivery to preschool children in
order to eliminate the variability in prescribed medication that eventually reaches patients.
The delivery to the lungs of a constant, reliably repeatable inhaled drug dose should be a
continuing aim for aerosol scientists and physicians.
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Employee perceptions of affirmative action in the Faculty of Health Science (University of Witwatersrand)06 June 2008 (has links)
The South African government introduced Affirmative Action in 1998 to redress historical workplace discrimination. The South African moral imperative considers Affirmative Action to be a necessary instrument of change influencing social and economic equality, which impacts on the development of Blacks. Affirmative Action is being researched in academic circles for reasons other than moral concern, which calls for a new breed of scientist to take equitable academic demographics into consideration. The exploratory study in question aimed to identify employees’ perceptions on Affirmative Action within the Faculty of Health Sciences at the University of Witwatersrand. The survey method was utilized in the study and opinions were elicited from 108 respondents in the Faculty. The results were analysed both qualitatively and quantitatively in order to gain a comprehensive insight into the perceptions. The focus of the study included: profile of the respondents, staffing and standards, employee development and mentorship, attitudes, training and culture. The findings of the investigation indicated that progress achieved by Affirmative Action within the Faculty was generally perceived to be slow. However, there appeared to be no problems related to holistic practices established in support of Affirmative Action. / Prof. W. Backer
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The perceptions of and courase evaluation of the MPH degree by former Wits students who graduated in the period 2001-2007Mutloane, Thomas Albert Mothei 25 November 2008 (has links)
Background: In 1998 the Wits Faculty of Health Science began to offer a master’s
programme in public health, through the School of Public Health, called the Master of
Public Health. (MPH). The aim of the degree is to prepare “professionals to play
leadership roles in the management, improvement and evaluation of health and the health
care system” and to respond “to the needs of the people of South Africa and the African
continent in their various living and working conditions”. Eight objectives have been set
for the degree and these will be gone into in detail. Admission requirements to the
programme are a bachelor’s degree of a minimum of four years duration in dentistry,
medicine, nursing, occupational therapy, physiotherapy, etc. The programme can be
offered on a full- or part-time basis. The following core modules are offered: Primary
Health Care & Social Context of Health; Health Measurement I & II; Environmental &
Occupational Health; Public Health Law & Health Systems Integration; Health Policy
&Policy Analysis; Health Systems & Decentralization; Health Management Theory &
Practice; Epidemiology; Health Care Financing etc. The primary motivation for this study
was to determine the level of satisfaction of MPH graduates with the degree that they
studied.
Methods: The study was a cross-sectional study design. It was a survey that entailed
using a pretested interview schedule or questionnaire. The study population was all MPH
graduates up until June 2007 (N = 80). The participants were contacted telephonically or
by e-mail by the researcher. The initial idea was to interview the participants
telephonically, but most preferred to have the prepared interview schedule e-mailed to
them. A Pilot Study (using 8 students) was conducted before commencement of the
actual study. The pilot study revealed that the study questionnaire, although long and
cumbersome, was do-able. A sample of 70 graduates was used and of these, 60 responded
i.e. response rate of 86%. The researcher e-mailed the interview schedule and the
information sheet which explained what the study was about and also made it clear that
even if they had initially agreed to participate, they could still opt out if they later
changed their minds. The information sheet further explained that their participation
would be kept strictly anonymous, only codes would be used.
The data gathering sheet (questionnaire) is in two parts: Part One is the “Course
Evaluation” and Part Two is the “Value of the Masters in Public Health to Your Career”.
Under Part One the candidates gave their views on the following: the content of various
courses or modules offered; the teaching methods applied by the School; academic
quality; administrative support; and research report support. Questions in each of these
subsections were such that a rating on a scale of 1 to 5 (5 being excellent and 1 poor) had
to be given and next to the score (rating) the candidate could also give a comment to
explain the rating or how they felt about what was asked. At the end of each of the subsections
are a number of open-ended questions that gave the candidate more scope for
further written or verbal input. Similarly, Part Two has a rating on a scale of 1 to 5 (5
being extremely valuable and 1 less valuable) in terms of the value the particular course
or module mentioned in the career of the graduate. There is also a “comment” portion
accompanying every question. And at the end of this part are six open-ended questions
aimed at eliciting more qualitative information based on the experiences of graduates post
graduation and specifically focusing on the working environment. One very important
question in this section is: “Would you or have you recommended this masters
programme to others”. There are only two possible answers to this question: “Yes” –
which signifies satisfaction with the programme, and “No” – which signifies unhappiness
with the programme. It is a very important question in gauging client satisfaction.
Results: On a rating of 1 to 5 (1 being poor whilst 5 is excellent the top rated modules were rated as follows under course evaluation: (i) Primary Health Care & Social Context
of Health: All respondents (60 i.e. 100%) rated this module and gave it a rating of 4.13
(83%) (ii) Health Policy and Policy Analysis: Although 40 (67%) out of 60 people
responded to this question, they gave it a rating of 4.25 (85%) (iii) Project Management
for Public Health Practitioners: It was given a 4.27 (85%) rating by 44 (73%) out of 60
participants. (iv) Management in Health and Health Services: This module was given a
rating of 3.83 (77%) by 58 (97%) out of 60 participants and (v) Introduction to
Management in Theory and Practice: It was rated at 3.82 (76%) by 32 (53%) of the 60
participants. The same top-rated above modules were rated as follows under “Value of
the Masters in Public Health (MPH) to your career” i.e. Part II of the questionnaire. (i)Primary Health Care & Social Context of Health: 3.26 (65%) as rated by 46 (77%) out 60
participants. (ii) Health Policy and Policy Analysis: 3.96 (79%) by 46 (77%) respondents
out of 60. (iii) Project Management for Public Health Practitioners: 3.26 (65%) as rated
by 46 (77%) out 60 participants. (iv) Management in Health and Health Services: 3.96
(79%) by 54 (90%) out of 60 participants.
Discussion: Various laudable written comments made by participants about each
module have been captured and recorded. These will be seen later. (i) Primary Health
Care & Social Context of Health: This module received a very high from all the
participants of the research study. The concepts of Primary Health Care and Social
Context of Health have clearly been taught and grasped. (ii) Health Policy and Policy
Analysis: This was the track that most graduates followed. It helped graduates understand
and be able to analyse various policy issues in their respective organizations. Emphasis
has not only been laid on policy formulation but also on policy implementation. (iii)
Project Management for Public Health Practitioners: This module scored a very high
rating under course evaluation. There is a perception that some public health services
could be run as projects in an endeavour to increase efficiency. (iv) Management in
Health and Health Services: A number of the students who come from the public health
sector to do MPH are in management positions already, although they may not have a
formal management qualification. Those who are not in management positions are
preparing themselves to go into management positions in future. This module is of great
assistance in preparing them for careers in management.
The study has revealed that 98% of participants have stated that they would or have
recommended the Wits MPH to others. And 80% of the participants have also stated that
there has been a positive change in their careers since acquiring the MPH qualification.
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Toll-like receptor genes and their pathway : role in susceptibility to pulmonary tuberculosis in a South African populationLucas, Lance Andrew 03 1900 (has links)
Thesis (MScMedSc)--Stellenbosch University, 2012. / Bibliography / ENGLISH ABSTRACT: The communicable disease tuberculosis (TB) is responsible for millions of deaths each year, on a
global scale. At present the contribution of host genetics in TB is generally accepted and, together
with environmental aspects (e.g. nutrition and crowding) and the causative bacterium,
Mycobacterium tuberculosis (M. tuberculosis); it will possibly have a hand in the outcome of
disease. Clearly, TB is a multifaceted disease and the repercussions for studying genetic
susceptibility are that many genes will potentially be implicated.
To date a variety of genes such as NRAMP1 and HLA have been implicated in influencing the host
response to TB, albeit with varying effects in different populations. Some of the more recently
implicated genes are the pattern recognition receptors, the Toll-like receptors (TLRs). Genetic
variation in theses genes has been associated with a myriad of different diseases, including those of
an infectious nature, such as TB. In the case of TB, TLR2 is the most prominent candidate with
TLR8 and 9 more recently implicated. One of the more well known genes implicated with TB is the
vitamin D receptor (VDR), as the antimicrobial gene cathelicidin (CAMP), one of the most
important agents of mycobacterial killing, has a VDR response element in its promoter. TLR2, VDR
and CAMP are all connected in a complex pathway essential for the host defence against M.
tuberculosis.
Nine single nucleotide polymorphisms (SNPs) in three TLR genes (TLR2,8 & 9) were investigated
via a case-control approach to determine their potential role in human genetic susceptiblity to TB in
the Coloured population of South Africa. The effect of the VDR polymorphism Cdx2 on the
expression of cathelicidin mRNA and protein expression was also investigated.
Three genes were found to contribute significantly to genetic host susceptibility in the Coloured
population of South Africa. An allelic association (p = 0.031) was observed for the TLR8 (located
on the X-chromosome) SNP rs3761624, with the A-allele being more prominent in females. Four
haplotypes of TLR8 were found to be significantly linked to TB susceptibility with the three SNP
haplotype rs3761624-rs3764879-rs3764880, specifically the allelic combination of G/C/A [p =
0.004, OR = 2.67(95% CI: 1.90-3.74)], showing a marked association (p = 0.001). The TLR9 introexon2
boundary SNP rs352139 was significantly associated with TB susceptiblity on a genotypic (P
= 0.02) and allelic scale [p = 0.05, OR=0.70; (95% CI: 0.55–0.90)], with the T allele more frequent in controls. The TLR9 two SNP haplotype consisting of rs5743836 and rs352139 was linked (p =
0.037) to TB susceptibility, specifically the combination of the alleles A/T [p = 0.013, OR=0.71;
(95% CI: 0.55–0.92)]. No gene-gene interaction between TLR2, TLR8 and TLR9 was observed. No
significant conclusions could be drawn from the analysis of the mRNA and protein expression of
CAMP in samples harbouring the different genotypes of the VDR polymorphism Cdx2.
Genetic variations in the TLR8 and 9 genes were identified as potential factors that influence
genetic host susceptibility to tuberculosis in the Coloured population of South Africa. / AFRIKAANSE OPSOMMING: Die oordragbare siekte tuberkulose (TB) is elke jaar verantwoordelik vir miljoene sterftes
wêreldwyd. Die invloed van die gasheer genoom op TB vatbaarheid word huidiglik aanvaar,
tesame met die invloed van omgewingsfaktore (dieet, oorbevolking ens.) en die bakterium
Mycobacterium tuberculosis (M. tuberculosis). Dit is duidelik dat TB ‘n veelvlakkigesiekte is wat
beïnvloed sal word deur ‘n menigte verskillende gene.
‘n Verskeidenheid gene is al betrek by TB genetiese vatbaarheid, onder andere NRAMP1 en HLA,
hoewel hul effekte in uiteenlopende bevolkings verskil. Sommige van die onlangse gene wat betrek
is in TB genetiese vatbaarheid is die Toll-like reseptore (TLRs). Genetiese variasie in hierdie gene
is geassosieer met ‘n wye verskeidenheid van siektes, insluitend aansteeklik van aard, onder andere
TB. In die geval van TB speel TLR2 ‘n prominente rol, terwyl TLR8 en TLR9 meer onlangs
geïmpliseer is. Een van die meer bestudeerde TB vatbaarheidsgene is die vitamiene D reseptor
geen (VDR). VDR is direk betrokke in die uitdrukking van die anti-mikrobiale geen cathelicidin
(CAMP),’n integrale komponent in die vernietiging van mikobakterieë. Die CAMP geen het ‘n
VDR respons-element in sy promotor. Die TLR2, VDR en CAMP gene word verbind deur ‘n
komplekse netwerk wat integraal is tot die liggaam se vermoë om TB af te weer.
Nege enkel nukleotied polimorfismes (ENPs) in drie gene (TLR2,8 & 9) is vir hierdie studie
ondersoek, deur gebruik te maak van ‘n pasiënt-kontrole assosiasiestudies, om te bepaal watter rol
hul speel in genetiese vatbaarheid vir TB in die Kleurling bevoling van Suid-Afrika, al dan nie. Die
invloed van die VDR polimorfisme Cdx2 op die uitdrukking van die mRNS (boodskapper
ribonukleïensuur) en proteïen van die geen CAMP is ook ondersoek.
Ons het gevind dat drie gene beduidend bygedra het tot genetiese vatbaarheid vir TB in die
Kleurling populasie. ‘n Alleel verwante assosiasie (p = 0.031) was gevind vir die TLR8 SNP
rs3761624, waar die A-alleel meer algemeen was in vroue. Vier haplotipes vir TLR8 het
beduidende assosiasies met TB vatbaarheid getoon. Die drie SNP haplotipe rs3761624-rs3764879-
rs3764880, spesifiek die alleel kombinasie C/G/A [p = 0.004, OR = 2.67(95% CI: 1.90-3.74)] het
sterk assosiasie (p = 0.001) met TB getoon. Die TLR9 intron-ekson2 grens SNP, rs352139 het
beduidende assosiasie met TB getoon op ‘n genotipiese (p = 0.02) sowel as alleliese skaal [p =
0.05, OR=0.70; (95% CI: 0.55–0.90)], met die T alleel meer algemeen in kontroles. Die twee SNP haplotipe bestaande uit rs5743836 en rs352139 het TB vatbaarheid beïnvloed (p = 0.037), spesifiek
die alleliese kombinasie van A/T [p = 0.013, OR=0.71; (95% CI: 0.55–0.92)]. Geen
noemenswaardige interaksies tussen TLR2, 8 en 9 is gevind nie. So ook is geen beduidende
resultate gevind vir die effek van die VDR SNP Cdx2 op die uitdrukking van CAMP mRNS en
proteïen nie.
Genetiese variasie in die TLR8 en 9 gene is geïdentifiseer as moontlike faktore wat gasheer
genetiese vatbaarheid vir TB in die Kleurlingbevolking van Suid-Afrika beïnvloed. / WW Roome Trust
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Undergraduate teaching and assessment needs in ethics and professionalism on clinical ward rounds involving medical students, Faculty of Health Sciences, Stellenbosch University (SU) : a nonexperimental descriptive study.Heyns, Louis 12 1900 (has links)
Thesis (MPhil)--Stellenbosch University, 2011. / ENGLISH ABSTRACT: Background: The theoretical / cognitive component of ethics and professionalism teaching to
undergraduate medical students at Stellenbosch University (SU) is well developed, but a concern exists
about the need for teaching and assessment of clinical ethics and professionalism on ward rounds. Some
teaching does take place during clinical rotations in the form of role modelling as part of the hidden
curriculum. Opportunities should be created for explicit teaching of ethics and professionalism beyond
the hidden curriculum. Assessment of the cognitive component of ethical and professionalism occurs,
but assessment of clinical ethics and professionalism during clinical rotations remains a challenge.
Methods: This was a non-experimental study and included three subgroups of undergraduate medical
students in their clinical years as well as a random sample of educators involved in clinical training.
Questionnaires were distributed to the students and educators. This was followed by focus group
interviews among the students.
Results: A majority of the students (88%) had indicated that they had experienced ethical and
professional dilemmas while working in the wards or during ward rounds. The main dilemmas revolved
around inadequate consent processes, lack of confidentiality and privacy, disrespect for patients, poor
communication and students being expected to perform tasks they were not trained for. An average of
64% of students indicated that ethical and professional issues were not discussed during the clinical
rotations in hospitals. Seventy-eight percent of students indicated that they did not feel free to discuss
their own feelings or beliefs on ward rounds. All of the educators felt that there was a need for
increased teaching and assessment of the medical students during their clinical rotations. Conclusions: Deliberate opportunities need to be created for teaching ethics and professionalism on
clinical ward rounds. This could be a shared responsibility between the clinical departments with
continuous input throughout the clinical years of study. Strong institutional support and commitment
are necessary to make the teaching sustainable and successful. Structured opportunities need to be
developed where students can discuss ethical and professional issues in a safe environment. Further
research is needed for the development of an appropriate curriculum and assessment tools. / AFRIKAANSE OPSOMMING: Geen opsomming
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Profesní kariéra a názory na studium prvních absolventů bakalářského studia oboru Všeobecná sestra na Zdravotně sociální fakultě Jihočeské univerzity. / The proffesional career and opinions about studies of the first graduates of bachelor studies General nurses at The Faculty of Health and Social Studies of The University of South Bohemia.JIRÁKOVÁ, Marcela January 2013 (has links)
The diploma work deals with the proffesional development of the first graduates of bachelor studies The General Nurse at The Faculty of Health and Social Studies of the University of South Bohemia since their graduation till the present. The goal of this work was to ascertain the opinions about the bachelor studies of the discipline General Nurse at the The Faculty of Health and Social Studies of the University of South Bohemia, namely of the first graduates of this discipline. The goal was to find out, how the studies and their succesfull graduation affected their proffesional career and social credit. Moreover to ascertain the attitude of the first graduates of the discipline The General Nurse at the The Faculty of Health and Social Studies of the University of South Bohemia to follow-up master's degree study Nursing care by selected clinical branches at The University of South Bohemia. The diploma work is divided into two parts ? the theoretic and empiric. The theoretic part deals with nursing and the conclusive part is educational. It includes the history and equipment of the nursing and the education of nurses in the Czech Republic, afterwards the problems of the profession of nurses and the related legislation . The educational part deals with the attitude as a social problem and the evaluation of the university education of the students themselves. In the empiric part of the diploma work were chosen both the quantitive and qualitative methods of an investigation research. The quantitive research had the form of a anonymous questionnaire for the first graduates of bachelor studies The General Nurse at The Faculty of Health and Social Studies of the University of South Bohemia. There were determined four assumptions. The results of the investigation have been processed into charts and tables. For the qualitative part of the survey research has been used in-depth unstructured interview, which was realised with the selected graduates. The results of the qualitative investigation have been adapted in the form of transcription of the interview. The results of this work can be used as an informational materiál for students and tutors of The Department of Nursing at The Faculty of Health and Social Studies of the University of South Bohemia. The results can help to be well informed in the education of nurses and to realise, which field of study needs to be strengthened.
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Postoje studentů denní formy studia Zdravotně sociální fakulty Jihočeské univerzity k vlastní uplatnitelnosti na trhu práce / Attitudes of Students selected fields Faculty of Health and Social Studies University of South Bohemia in České Budějovice for their own employability in the Labor MarketKOIŠOVÁ, Lenka January 2017 (has links)
In my thesis, I am finding out about the attitudes of students of the health and social faculty towards their own future occupation prospects. Although the unemployment situation in the Czech Republic as well as the situation in the South Region is favorable, graduates and young people are among the most vulnerable groups in the labor market. The first chapter describes the theoretical background of this issue. This part defines the overall unemployment problems of the Czech Republic, unemployment in the South Region. It describes the labor market and students situation is described based on the educational attainment and then their situation in the Czech Republic is compared to the similar situation abroad. Then it also describes the faculty and defines the issues of helping professions covered by the fields of the faculty. The aim of my thesis was to find out what the students of the faculty imagine when asked of their future occupation. They would like to stay in the field which they graduated from and then why they would want to stay in it or why not. The results show that students of the faculty want to stay in the field they graduated from on the labor market in the future. The research was conducted via questionnaire. In the practical part of the thesis I compared the attitudes of students of health and social fields. I also compared the attitudes of students who are studying in bachelor's program and students who continue their studies in the follow-up study. When it comes to comparison between the social and health studies, it is possible to see the differences in the attitudes of students, as well as the comparison of bachelor and master programs. Thesis may be beneficial for the employment deparment of Czech Republic and for the health and social faculty. Furthermore it may also be beneficial for representatives of state administration who monitor and control the whole system of tertiary education.
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Application of zirconium-coated titanium wires as restorative orthodontic materialsAli, Khaled Abedela Mahdi January 2013 (has links)
Thesis submitted in fulfillment of the requirements for the degree
Magister of Technology: Dental Technology
In the Faculty of Health & Wellness Sciences
At the Cape Peninsula University of Technology
2013 / Orthodontic archwires are made from different alloys. It is now possible to match phases of treatment with orthodontic archwires according to its mechanical properties. On this basis, the titanium molybdenum alloys (TMA) in its beta phase have an excellent combination of strength and flexibility when used as archwires to apply biomechanical forces that affect tooth movement. It has recently gained increased popularity in orthodontic treatment. There are, however, disadvantages associated with the use of orthodontic archwires, such as high surface roughness, which increases friction at the archwire-brackets interface during the sliding process. The surface roughness of dental materials is of utmost importance. Properties such as desirable tensile strengths, load deflection, hardness and low modulus of elasticity and resistance against corrosion & wear determine the area of the contact surface, thereby influencing the friction.
The main object of this study was to improve the strength and surface roughness of the beta-titanium orthodontic archwires (β-Ti III) and timolium archwires (TIM), taking into account of retention of the archwires strength. The following tasks were performed. Layers of Zr were deposited on the β-Ti archwires and compared with the archwire strength before and after Zr deposition. The structure of selected archwires and its composition and surface roughness was investigated before and after Zr deposition, using scanning electron microscopy (SEM) and atomic force microscopy (AFM). The force of selected archwires before and after deposition with layers of Zr by Hounsfield deflection testing was studied.
Two commercially available orthodontic archwires were used in this study, namely, β-Ti III and TIM orthodontic archwires. The archwires were cut into 25 mm long specimens. In this study, the electron beam-physical vapour deposition (EB-PVD) technique was applied to deposit pure Zr (thicknesses of 5, 10, 25 and 50 nm) on selected archwires and the effects thereof were investigated using AFM, SEM and the Hounsfield deflection test. Results of SEM and AFM analysis and deflection tests showed significant differences between Zr-coated archwires compared with uncoated archwires. Zr-coated archwires (5, 10, 25 and 50 nm depositions) had reduced surface roughness compared with uncoated archwires. A high load deflection rate was exhibited by the coated β-Ti III archwires and a low load deflection rate was exhibited by the coated TIM archwires. There was a difference in load deflection rate between the coated and uncoated archwires. Deposition of 5, 10, 25 and 50 nm Zr on both types of β-Ti orthodontic archwires is recommended for even sliding mechanics due to resulting reduced surface roughness with a good load deflection rate compared with uncoated β-Ti orthodontic archwires.
KEYWORDS
Surface roughness
Zirconium
Titanium
Deflection test
Beta titanium orthodontic archwires
Orthodontic archwires alloys
Coated materials
Electron beam-physical vapour deposition
Scanning electron microscopy
Atomic force microscopy
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Subjektivní vliv sociální reklamy na studenty Jihočeské univerzity v Českých Budějovicích. / Subjective Influence of Social Advertising to Students of University of South Bohemia in České Budějovice.ZAJACOVÁ, Veronika January 2018 (has links)
The diploma thesis deals with the less known type of advertising - the social advertising. The social advertising uses mostly emotional appeals to raise awareness about societal problems, bad habits of people and strives for the behavioural change aiming to make the contemporary world better. The diploma thesis consists of a theoretical and a practical part, whilst the theoretical part offers a comprehensive view not only on the social advertising but partly on the advertising in general as well. It explains the term of social advertising, compares it to the commercial advertising, describes its historical development and defines the subjects of the social advertising. The theoretical part further explains how the social advertising influences the society, which is mostly done by the emotional expression of the given problem and by advertising appeals. Approached are also the specific advertising campaigns - by the most common typologisation of social advertising themes. The research was conducted using surveys aiming to find out whether there are any differences in the awareness of social advertising by students of the HSS SBU and the FE SBU all together with finding out whether it is possible to talk about a higher social advertising influence on students of the HSS SBU. The results were in accordance with these hypothesises which can prove the existence of knowledge differences of students about the social advertising based on their field of study and the fact that the social advertising has bigger influence on students of the health and social fields of study. Answers of respondents from both faculties were often different. On the other hand, students from both HSS SBU and FE SBU have shown the same answers regarding the attitude towards the social advertising. It is possible to make a statement that the social advertising seems beneficial to both HSS SBU and FE SBU students as well and they would like to be in contact with it more often. The students of HSS SBU have chosen to perform the helping professions for their carrier which demands also personal traits that can be e.g. the social feeling and the desire to help. The research brought the finding, that the students care about the social problems and that the social advertising fulfils its purpose which is raising awareness about the societal problems that should get known by people this way.
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