382 research outputs found
Illness Stigma, Social Connectedness, and Health in People living with Chronic Illness: A Structural Equation Model
The complexity of chronic or unexplained conditions may lead to potential stigma for those suffering long-term symptoms as they do not follow the expected pattern of recovery following diagnosis and treatment. Experiencing such illness-related stigma has potential for leading to a belongingness identity of detachment with implications for health across physical, social, and psychological dimensions. This study aimed to examine the relationship between stigma, social connection, mental health, physical health, and social functioning in a group of 231 participants with ongoing symptoms of chronic illness through structural equation modeling. The fit indices all suggest that the model reasonably fits the data with greater stigma predicting poorer social connectedness, which in turn mediated quality of life across all areas of mental, social, and physical health. The pathway through social connection provided stronger results than the direct path for mental health and social functioning suggesting that social connectedness has a greater influence on these factors than stigma alone. Findings situate social connectedness as a psychosocial factor that is inversely associated with illness-related stigma and support theoretical predictions that this aspect of belongingness predicts all aspects of physical, social and mental health. Further theoretical development on stigma within the realm of health psychology may prove advantageous to increasing knowledge and producing more efficacious interventions
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Biphasic bone graft substitute in revision total hip arthroplasty with significant acetabular bone defects : a retrospective analysis.
AIMS: Large acetabular bone defects encountered in revision total hip arthroplasty (THA) are challenging to restore. Metal constructs for structural support are combined with bone graft materials for restoration. Autograft is restricted due to limited volume, and allogenic grafts have downsides including cost, availability, and operative processing. Bone graft substitutes (BGS) are an attractive alternative if they can demonstrate positive remodelling. One potential product is a biphasic injectable mixture (Cerament) that combines a fast-resorbing material (calcium sulphate) with the highly osteoconductive material hydroxyapatite. This study reviews the application of this biomaterial in large acetabular defects. METHODS: We performed a retrospective review at a single institution of patients undergoing revision THA by a single surgeon. We identified 49 consecutive patients with large acetabular defects where the biphasic BGS was applied, with no other products added to the BGS. After placement of metallic acetabular implants, the BGS was injected into the remaining bone defects surrounding the new implants. Patients were followed and monitored for functional outcome scores, implant fixation, radiological graft site remodelling, and revision failures. RESULTS: Mean follow-up was 39.5 months (36 to 71), with a significant improvement in post-revision function compared to preoperative function. Graft site remodelling was rated radiologically as moderate in 31 hips (63%) and strong in 12 hips (24%). There were no cases of complete graft site dissolution. No acetabular loosening was identified. None of the patients developed clinically significant heterotopic ossification. There were twelve reoperations: six patients developed post-revision infections, three experienced dislocations, two sustained periprosthetic femur fractures, and one subject had femoral component aseptic loosening. CONCLUSION: Our series reports bone defect restoration with the sole use of a biphasic injectable BGS in the periacetabular region. We did not observe significant graft dissolution. We emphasize that successful graft site remodelling requires meticulous recipient site preparation.Cite this article: Bone Jt Open 2022;3(12):991-997
Neuroinflammatory Gene Expression Alterations in Anterior Cingulate Cortical White and Gray Matter of Males With Autism Spectrum Disorder
Evidence for putative pathophysiological mechanisms of autism spectrum disorder (ASD), including peripheral inflammation, blood–brain barrier disruption, white matter alterations, and abnormal synaptic overgrowth, indicate a possible involvement of neuroinflammation in the disorder. Neuroinflammation plays a role in the development and maintenance of the dendritic spines involved in glutamatergic and GABAergic neurotransmission, and also influences blood–brain permeability. Cytokines released from microglia can impact the length, location or organization of dendritic spines on excitatory and inhibitory cells as well as recruit and impact glial cell function around the neurons. In this study, gene expression levels of anti- and pro-inflammatory signaling molecules, as well as oligodendrocyte and astrocyte marker proteins, were measured in both gray and white matter tissue in the anterior cingulate cortex from ASD and age-matched typically developing (TD) control brain donors, ranging from ages 4 to 37 years. Expression levels of the pro-inflammatory gene, HLA-DR, were significantly reduced in gray matter and expression levels of the anti-inflammatory gene MRC1 were significantly elevated in white matter from ASD donors as compared to TD donors, but neither retained statistical significance after correction for multiple comparisons. Modest trends toward differences in expression levels were also observed for the pro-inflammatory (CD68, IL1β) and anti-inflammatory genes (IGF1, IGF1R) comparing ASD donors to TD donors. The direction of gene expression changes comparing ASD to TD donors did not reveal consistent findings implicating an elevated pro- or anti-inflammatory state in ASD. However, altered expression of pro- and anti-inflammatory gene expression indicates some involvement of neuroinflammation in ASD.
Lay Summary: The anterior cingulate cortex is an integral brain region in modulating social behaviors including nonverbal communication. The study found that inflammatory gene expression levels were altered in this brain region. We hypothesize that the inflammatory changes in this area could impact neuronal function. The finding has future implications in using these molecular markers to identify potential environmental exposures and distinct cell differences in autism
Mathematical Morsels: Solutions to Tasks From the Fall Issue
In this column, we share solutions submitted by our readers for tasks provided in
the Mathematical Morsels column of our Fall issue. The editors wish to thank those who took
the time to submit tasks and YouTube solutions
Advances in genetics: widening our understanding of prostate cancer
Prostate cancer is a leading cause of cancer-related death in Western men. Our understanding of the genetic alterations associated with disease predisposition, development, progression, and therapy response is rapidly improving, at least in part, owing to the development of next-generation sequencing technologies. Large advances have been made in our understanding of the genetics of prostate cancer through the application of whole-exome sequencing, and this review summarises recent advances in this field and discusses how exome sequencing could be used clinically to promote personalised medicine for prostate cancer patients.</ns4:p
Performance of the CMS Cathode Strip Chambers with Cosmic Rays
The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device
in the CMS endcaps. Their performance has been evaluated using data taken
during a cosmic ray run in fall 2008. Measured noise levels are low, with the
number of noisy channels well below 1%. Coordinate resolution was measured for
all types of chambers, and fall in the range 47 microns to 243 microns. The
efficiencies for local charged track triggers, for hit and for segments
reconstruction were measured, and are above 99%. The timing resolution per
layer is approximately 5 ns
Germline whole exome sequencing and large-scale replication identifies FANCM as a likely high grade serous ovarian cancer susceptibility gene.
We analyzed whole exome sequencing data in germline DNA from 412 high grade serous ovarian cancer (HGSOC) cases from The Cancer Genome Atlas Project and identified 5,517 genes harboring a predicted deleterious germline coding mutation in at least one HGSOC case. Gene-set enrichment analysis showed enrichment for genes involved in DNA repair (p = 1.8×10-3). Twelve DNA repair genes - APEX1, APLF, ATX, EME1, FANCL, FANCM, MAD2L2, PARP2, PARP3, POLN, RAD54L and SMUG1 - were prioritized for targeted sequencing in up to 3,107 HGSOC cases, 1,491 cases of other epithelial ovarian cancer (EOC) subtypes and 3,368 unaffected controls of European origin. We estimated mutation prevalence for each gene and tested for associations with disease risk. Mutations were identified in both cases and controls in all genes except MAD2L2, where we found no evidence of mutations in controls. In FANCM we observed a higher mutation frequency in HGSOC cases compared to controls (29/3,107 cases, 0.96 percent; 13/3,368 controls, 0.38 percent; P=0.008) with little evidence for association with other subtypes (6/1,491, 0.40 percent; P=0.82). The relative risk of HGSOC associated with deleterious FANCM mutations was estimated to be 2.5 (95% CI 1.3 - 5.0; P=0.006). In summary, whole exome sequencing of EOC cases with large-scale replication in case-control studies has identified FANCM as a likely novel susceptibility gene for HGSOC, with mutations associated with a moderate increase in risk. These data may have clinical implications for risk prediction and prevention approaches for high-grade serous ovarian cancer in the future and a significant impact on reducing disease mortality
Putting Life in Years (PLINY): a randomised controlled trial and mixed-methods process evaluation of a telephone friendship intervention to improve mental well-being in independently living older people
YesBackground: Social isolation in older adults is associated with morbidity. Evaluating interventions to
promote social engagement is a research priority.
Methods: A parallel-group randomised controlled trial was planned to evaluate whether telephone
friendship (TF) improves the well-being of independently living older people. An internal pilot aimed to
recruit 68 participants by 30 September 2012, with 80% retained at 6 months. Randomisation was web
based and only analysts were blind to allocation. A service provider was contracted to train 10 volunteer
facilitators by 1 April 2012 and 10 more by 1 September 2012. Participants were aged > 74 years with
good cognitive function and living independently in an urban community. The intervention arm of the
trial consisted of manualised TF with standardised training: (1) one-to-one befriending (10- to 20-minute
calls once per week for up to 6 weeks made by volunteer facilitators) followed by (2) TF groups of
six participants (1-hour teleconferences once per week for 12 weeks facilitated by the same volunteer).
Friendship groups aimed to enhance social support and increase opportunities for social interaction
to maintain well-being. This was compared with usual health and social care provision. The primary
clinical outcome was the Short Form questionnaire-36 items (SF-36) mental health dimension score at
6 months post randomisation. Qualitative research assessing intervention acceptability (participants)
and implementation issues (facilitators) and an intervention fidelity assessment were also carried out.
Intervention implementation was documented through e-mails, meeting minutes and field notes.
Acceptability was assessed through framework analysis of semistructured interviews. Two researchers
coded audio recordings of telephone discussions for fidelity using a specially designed checklist.
Results: In total, 157 people were randomised to the TF group (n = 78) or the control group (n = 79).
Pilot recruitment and retention targets were met. Ten volunteers were trained by 1 September 2012; after
volunteer attrition, three out of the 10 volunteers delivered the group intervention. In total, 50 out of the
78 TF participants did not receive the intervention and the trial was closed early. A total of 56 people
contributed primary outcome data from the TF (n = 26) and control (n = 30) arms. The mean difference in SF-36 mental health score was 9.5 (95% confidence interval 4.5 to 14.5) after adjusting for age, sex and
baseline score. Participants who were interviewed (n = 19) generally declared that the intervention was
acceptable. Participant dissatisfaction with closure of the groups was reported (n = 4). Dissatisfaction
focused on lack of face-to-face contact and shared interests or attitudes. Larger groups experienced better
cohesion. Interviewed volunteers (n = 3) expressed a lack of clarity about procedures, anxieties about
managing group dynamics and a lack of confidence in the training and in their management and found
scheduling calls challenging. Training was 91–95% adherent with the checklist (39 items; three groups).
Intervention fidelity ranged from 30.2% to 52.1% (28–41 items; three groups, three time points),
indicating that groups were not facilitated in line with training, namely with regard to the setting of
ground rules, the maintenance of confidentiality and facilitating contact between participants.
Conclusions: Although the trial was unsuccessful for a range of logistical reasons, the experience gained is
of value for the design and conduct of future trials. Participant recruitment and retention were feasible.
Small voluntary sector organisations may be unable to recruit, train and retain adequate numbers of
volunteers to implement new services at scale over a short time scale. Such risks might be mitigated by
multicentre trials using multiple providers and specialists to recruit and manage volunteers.Funding for this study was provided by the Public Health Research programme of the National Institute for Health Research
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