2,685 research outputs found
Leading the Play: Development of a Method Supporting Expression and Control with Adults with Dementia
This paper explores the concept of client-led play with older adults with dementia and its possible impact on an individual’s ability to express enjoyment and sense of control. Expressive arts therapy is explored as a possible natural vehicle for providing client-led play groups to older adults with dementia. While research is limited regarding client-led play specifically, there has been significant research supporting the use of the creative arts with individuals with dementia, as it provides opportunities for non-verbal expression and spontaneous creativity. This paper argues that the arts have a natural connection to play through the use of the imagination and in-the-moment choice making. The author developed and implemented two play-based interventions with adults with dementia at an assisted living facility in Massachusetts. This paper will discuss the literature that informed the method, what took place during the implementation, and what was learned from observing and experiencing client-led play with adults with dementia
Emotion regulation among adults with asthma: Links with short-acting inhaler medication overuse and utilization of acute medical care
Effective control of asthma symptoms requires daily self-management activities, including use of short-acting or “rescue” inhaled medications. Overuse of short-acting inhaled medications, such as albuterol, can have negative side-effects, including respiratory infections and worse asthma symptom control. Existing research suggests that emotion plays an important role in airway inflammation and asthma symptom control. The objective of this study was to determine whether difficulties regulating emotion was associated with overuse of short-acting inhaled medications and acute medical care usage in adults with asthma. The sample included 401 adults with asthma recruited from an online panel of adults with chronic respiratory disease. Respondents completed a survey that included measures of short-acting medication use, acute medical service use, and emotion regulation (Difficulties in Emotion Regulation Scale [DERS]). Sequential binary logistic regression models were used to examine the association between DERS scores with two indicators of short-acting inhaled medication overuse: using \u3e3 canisters of short-acting inhaled medications in the past three months or self-reported overuse (i.e., using short-acting inhaled medications more than prescribed) while controlling for patient characteristics (current smoking and health insurance status) and comorbid mental health conditions (probable depression and probable anxiety). The results showed that greater difficulties in emotion regulation was significantly associated with greater odds of using more than three canisters in the past three months (AOR = 1.023, 95%CI [1.012, 1.035], p \u3c .001) and using short-acting inhaled medications more than prescribed (AOR = 1.024, 95%CI [1.014, 1.035], p \u3c .001) as well as with greater odds of emergency department visits (AOR = 1.018, 95%CI [1.009, 1.028], p AOR = 1.017, 95%CI [1.007, 1.028], p=.001) in the prior 12-months – even after adjusting for probable depression and probable anxiety, current smoking, and health insurance status. In conclusion, emotion dysregulation may play an important role in overuse of short-acting inhaled medications and acute medical care utilization among adults with asthma. Evidence-based interventions to reduce difficulties in emotion regulation may help improve problematic patterns of short-acting medication overuse among adults with asthma
Frequency over function : raised levels of CD127low/- regulatory T cells in the tumour microenvironment compared with the periphery of head and neck cancer patients
Objective: Regulatory T cells (Tregs) are known to infiltrate the tumour microenvironment of many cancers, including head and neck malignancies, and are thought to contribute to the host's impaired anti-tumour immune response. However, their immunosuppressive function remains poorly understood within the tumour microenvironment and this study aimed to address this. Methods: The frequency and suppressive capacity of two CD4?CD127low/- Treg populations, separated on the basis of different levels of CD25 expression (CD25inter and CD25high), from the tumour/node microenvironment and peripheral circulation of newly-presenting head and neck squamous cell carcinoma patients (n=19), were assessed using multicolour flow cytometry. Results: The proportion of Tregs (CD4?CD25high/?interCD127low/-) in the tumour/node microenvironment was significantly elevated compared with the peripheral circulation (p<0.001) and similar percentages were present in both the primary tumour and metastatic lymph node. The percentage of suppression induced by Tregs isolated from tumour associated nodes on the proliferation of nodal effector T cells was similar to that of peripheral Tregs on peripheral effector T cells. However, when the suppressive activity of both nodal and peripheral Tregs was compared on the same peripheral effectors, peripheral Tregs suppressed proliferation to a greater extent. Conclusion: This work shows that the recruitment and percentages of tumour infiltrating Tregs are key factors in modulating the immune environment of head and neck tumours
The Critical Middle Years and the Relationship of Early Access to Algebra on High School Math Course Completion and College Readiness
Many students who enroll in higher education are unprepared to meet the challenges of postsecondary education. The probability that students will make a successful transition from high school to college is linked to the degree to which their secondary educational experiences have prepared them for the expectations and demands they will encounter in college. National findings provide continuing evidence that focusing on improving student achievement in mathematics will positively impact college readiness. The main problem addressed in this quantitative study was how educators can best prepare students for college readiness. Since college readiness is highly dependent upon math achievement in middle schools, postsecondary educators need additional research that explores how math curricula may ultimately impact the readiness of their college students. Therefore, seemingly benign decisions about placement of students in middle school math may ultimately impact greatly on their college readiness. In addition, the study focused on the implications of those placement decisions. Chi-square Automatic Interaction Detection (CHAID) was used to determine those variables that were most significantly associated with students\u27 math-related college readiness as evidenced by advanced mathematics coursework taken beyond Algebra I
Measuring the response of human head and neck squamous cell carcinoma to irradiation in a microfluidic model allowing customized therapy
Radiotherapy is the standard treatment for head and neck squamous cell carcinoma (HNSCC), however, radioresistance remains a major clinical problem despite significant improvements in treatment protocols. Therapeutic outcome could potentially be improved if a patient's tumour response to irradiation could be predicted ex vivo before clinical application. The present study employed a bespoke microfluidic device to maintain HNSCC tissue whilst subjecting it to external beam irradiation and measured the responses using a panel of cell death and proliferation markers. HNSCC biopsies from five newly-presenting patients [2 lymph node (LN); 3 primary tumour (PT)] were divided into parallel microfluidic devices and replicates of each tumour were subjected to single-dose irradiation (0, 5, 10, 15 and 20 Gy). Lactate dehydrogenase (LDH) release was measured and tissue sections were stained for cytokeratin (CK), cleaved-CK18 (cCK18), phosphorylated-H2AX (λH2AX) and Ki.67 by immunohistochemistry. In addition, fragmented DNA was detected using terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL). Compared with non.irradiated controls, higher irradiation doses resulted in elevated CK18-labelling index in two lymph nodes [15 Gy; 34.8% on LN1 and 31.7% on LN2 (p=0.006)] and a single laryngeal primary tumour (20 Gy; 31.5%; p=0.014). Significantly higher levels of DNA fragmentation were also detected in both lymph node samples and one primary tumour but at varying doses of irradiation, i.e., LN1 (20 Gy; 27.6%; p=0.047), LN2 (15 Gy; 15.3%; p=0.038) and PT3 (10 Gy; 35.2%; p=0.01). The λH2AX expression was raised but not significantly in the majority of samples. The percentage of Ki.67 positive nuclei reduced dose-dependently following irradiation. In contrast no significant difference in LDH release was observed between irradiated groups and controls. There is clear interand intra-patient variability in response to irradiation when measuring a variety of parameters, which offers the potential for the approach to provide clinically valuable information
Prelicensure Nursing Students’ Perceptions of a Rapid Transition to an Online Learning Environment
The transition to a fully online environment after the spread of the COVID-19 pandemic left all educators with the need to quickly transition didactic classes to the online environment and attempt to understand and utilize online teaching modalities. Online learning has only recently become integrated into nursing education, creating a gap in literature in relation to the most appropriate strategies for online course delivery, specifically in prelicensure nursing. This chapter explores the background to the project, types of learning environments, definitions of terms utilized, and purpose of the secondary analysis
Maintenance of head and neck tumor on-chip: gateway to personalized treatment?
Aim: Head and neck squamous cell carcinomas (HNSCC) are solid tumors with low overall survival (40–60%). In a move toward personalized medicine, maintenance of tumor biopsies in microfluidic tissue culture devices is being developed. Methodology/ results: HNSCC (n = 15) was dissected (5–10 mg) and either analyzed immediately or cultured in a microfluidic device (37°C) for 48 h. No difference was observed in morphology between pre- and postculture specimens. Dissociated samples were analyzed using trypan blue exclusion (viability), propidium iodide flow cytometry (death) and MTS assay (proliferation) with no significant difference observed highlighting tissue maintenance. Computational fluid dynamics showed laminar flow within the system. Conclusion: The microfluidic culture system successfully maintained HNSCC for 48 h, the culture system will allow testing of different treatment modalities with response monitoring. Lay abstract: Head and neck cancers often have a poor treatment outcome. In order to study the response of the tissue, a miniaturized culture system has been developed to keep a small piece of tumor alive. In the current study, we show that small pieces of cancer tissue can be maintained in the system, using tissue structure and viability of single cells as a guide. In future work, patient equivalent treatments can be applied to these microculture systems to investigate individual patient tumor responses, which could help to guide treatment selection
Survival estimates of Northern Gannets Morus bassanus in Alderney: big data but low confidence
Inhibition of Human Immunodeficiency virus replication through small RNA-induced gene silencing of HIV-1 Tat specific factor 1
Ph.D., Faculty of Health Sciences, University of the Witwatersrand, 2011The
HIV-‐1
pandemic
continues
unabated.
Although
treatments
exist
that
can
substantially
alleviate
the
morbidity
and
mortality
associated
with
HIV,
there
is
still
a
need
for
improved
anti-‐HIV
treatments
that
reduce
toxicities
and
administration
frequency
and
mediate
sustained
inhibition
of
viral
replication.
Given
the
high
mutability
and
variability
of
the
virus,
a
strategy
that
is
garnering
increasing
focus
is
the
targeting
of
host
factors
that
the
virus
requires
to
replicate,
so-‐called
HIV-‐dependency
factors
(HDFs).
It
is
hoped
this
will
reduce
the
emergence
of
viral
drug
resistance.
A
number
of
genome-‐wide
screens
have
been
performed
to
identify
HDFs,
although
many
remain
to
be
validated,
particularly
in
relevant
cells
lines.
An
objective
of
this
thesis
was
to
validate
three
host
factors
as
HDFs,
in
both
TZM-‐bl
reporter
and
T
cell-‐derived
cell
lines,
and
to
examine
their
potential
as
anti-‐HIV-‐1
therapeutic
targets
through
exploitation
of
the
cellular
gene
silencing
pathway,
RNA
interference
(RNAi).
These
were
HIV-‐1
Tat
specific
factor
1
(HTATSF1),
DEAD
(Asp-‐Glu-‐Ala-‐Asp)
box
polypeptide
3,
X-‐
linked
(DDX3X)
and
SWI/SNF
related,
matrix
associated,
actin
dependent
regulator
of
chromatin,
subfamily
b,
member
1
(SMARCB1),
selected
because
they
had
been
previously
implicated
in
HIV-‐
1
pathogenesis.
The
well-‐characterised
HDF,
PC4
and
SFRS1
interacting
protein
1
(PSIP1)/lens
epithelium-‐derived
growth
factor
(LEDGF)/p75,
was
included
in
the
study
as
a
positive
control.
Cassettes
expressing
short
hairpin
RNAs
(shRNAs)
targeting
the
four
host
proteins
were
generated,
although
shRNAs
did
not
suppress
endogenous
ddx3x
mRNA
levels.
The
ability
of
shRNAs
to
inhibit
HIV-‐1
replication
in
the
reporter
cell
line,
TZM-‐bl,
was
examined.
These
HeLa-‐
derived
cells
are
permissive
for
R5-‐tropic
HIV-‐1
infection
and
contain
an
integrated
luciferase
gene
driven
by
the
viral
promoter.
shRNAs
mediated
a
dose-‐dependent
inhibition
of
luciferase
activity
in
cells
infected
with
a
HIV-‐1
subtype
B
molecular
clone
and,
although
production
of
the
viral
protein
p24
was
unaltered,
infectious
particle
production
was
decreased
in
cells
treated
with
a
shRNA
suppressing
HTATSF1.
Little
effect
was
observed
with
a
shRNA
targeting
SMARCB1,
suggesting
that
this
may
not
function
as
an
HDF
under
these
conditions.
No
effect
on
infectious
particle
production
was
seen
with
the
shRNA
targeting
PSIP1,
which
was
a
result
of
the
long
half-‐
life
of
this
protein,
highlighting
a
limitation
of
using
such
reporter
systems
for
HDF
validation.
Importantly,
shRNAs
were
not
associated
with
any
cytotoxic
effects
in
TZM-‐bl
cells.
Whether
HTATSF1
is
a
potential
therapeutic
target
was
interrogated
further
in
the
more
relevant
T
cell-‐derived
SupT1
cell
line.
Lentiviruses
were
used
to
generate
populations
where
>90%
had
one
copy
of
the
integrated
shRNA
expression
cassette.
Replication
of
the
subtype
B
molecular
clone
p81A-‐4
was
significantly
inhibited
in
the
shH1-‐expressing
SupT1
cell
line,
which
targets
HTATSF1,
for
over
14
days
post-‐infection,
although
inhibition
was
not
as
pronounced
asthat
observed
in
the
shP1-‐expressing
SupT1
cell
line,
which
targets
PSIP1.
In
contrast
to
a
previous
report,
no
change
in
the
ratio
of
unspliced
to
singly-‐
or
multiply-‐spliced
HIV-‐1
transcripts
were
detected
in
shH1-‐expressing
SupT1
cells,
suggesting
that
HTATSF1
does
not
function
as
a
splicing
cofactor
in
this
system.
A
slight
rebound
in
p24
levels
at
14
days
post-‐infection
was
accompanied
by
increased
HTATSF1
expression
and
a
decrease
in
the
percentage
of
cells
with
transgene
expression
in
the
population.
In
addition,
there
was
a
slight
decrease
in
shH1-‐derived
guide
strand
expression,
but
no
change
in
transcription
rates
of
the
htatsf1
gene,
suggesting
that
cells
within
the
population
with
shH1
expression
and
HTATSF1
suppression
may
have
a
growth
disadvantage.
Thus,
although
this
work
demonstrates
for
the
first
time
that
HTATSF1
functions
as
an
HDF
in
T
cell-‐derived
SupT1
cells,
it
may
not
constitute
a
viable
therapeutic
target.
A
second
objective
of
this
thesis
was
to
examine
the
feasibility
of
transcriptional
gene
silencing
(TGS)
of
HDFs
as
an
anti-‐HIV
strategy.
TGS
is
a
small
RNA-‐induced
gene
silencing
pathway
that
operates
through
chromatin
remodelling
with
the
potential
to
mediate
long-‐term
silencing
of
gene
expression.
Thus,
its
application
may
reduce
the
frequency
of
drug
administration
and
associated
toxicities.
Short
interfering
RNAs
(siRNAs)
targeting
the
htatsf1
promoter
were
able
to
reduce
target
mRNA
expression,
which
was
accompanied
by
decreased
htatsf1
transcription
rates
in
HEK293T
cells,
suggesting
silencing
via
a
TGS
mechanism.
The
htatsf1
silencing
inhibited
infectious
HIV-‐1
particle
production
from
TZM-‐bl
cells.
This
work
provides
proof
of
principle
that
TGS
induction
at
a
HDF
may
inhibit
HIV-‐1
replication.
siRNAs
targeting
the
ddx3x
promoter
did
not
induce
TGS.
To
examine
whether
gene
susceptibility
to
TGS
may
be
influenced
by
promoter
architectures,
49
promoter
features
were
examined
for
enrichment
in
genes
at
which
small
RNA-‐induced
TGS
has
been
reported.
Initially,
the
TGS
group
was
compared
to
a
random
set
of
2,000
promoters
and
then
all
other
promoters
in
the
genome.
To
control
for
gene
activation,
two
further
analyses
were
performed
comparing
the
TGS
group
features
to
those
from
promoters
active
in
the
THP-‐1
cell
line
and
housekeeping
genes.
Whilst
difficult
to
ascribe
differences
between
the
TGS
group
and
the
control
groups
to
anything
beyond
a
variation
in
the
proportion
of
active
genes
within
each
group,
there
was
enrichment
for
certain
promoter
features
that
are
independent
of
activity;
the
TGS
group
was
characterised
by
broad
transcription
start
regions,
high
CpG
content
and
a
single
expression
profile.
Moreover,
the
fraction
of
promoters
with
reported
non-‐coding
RNA
overlap
was
greater
in
the
TGS
group
than
the
control
groups.
Thus,
there
is
some
evidence
that
a
number
of
promoter
features
are
associated
with
TGS
susceptibility.
It
is
hoped
this
novel
analysis
will
facilitate
selection
of
future
TGS
targets,
including
HDFs.
In
summary,
the
work
presented
in
this
thesis
paves
the
way
for
development
of
improved
anti-‐HIV
therapies
involving
HDF-‐targeted
TGS-‐based
gene
therapies
that
mediate
sustained
inhibition
of
the
virus
The Role of Chemokines in Thyroid Carcinoma
© Copyright 2017, Mary Ann Liebert, Inc. 2017. The global incidence of thyroid cancer is increasing, and metastatic spread to the lymph nodes is common in papillary thyroid carcinoma. The metastatic course of thyroid carcinoma is an intricate process involving invasion, angiogenesis, cell trafficking, extravasation, organ specific homing, and growth. A key aspect in this process involves a multitude of interactions between chemokines and their receptors. Chemokines are a group of small proteins, which act to elicit normal physiologic and immune responses principally through recruitment of specific cell populations to the site of infection or malignancy. Thyroid cancer cells, like other tumors, possess the ability to corrupt the chemokine system to their advantage by altering cell movement into the tumor microenvironment and affecting all aspects of thyroid cancer progression
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