Compression garment wear and sensory variables after burn: a single-site study.

OBJECTIVE: Compression garments are well accepted as routine practice for scar management after burn. In a recent systematic review, six main reasons for compression garment non-adherence were identified including sensory disturbances. To further understand the impact of sensory issues, the aim of the present study is to investigate associations between sensory variables and compression garment wear. METHOD: Adults (N = 117) attending a quaternary adult burns outpatient clinic completed: The Adolescent/Adult Sensory Profile; a custom-designed compression garment wear questionnaire; and three quantitative sensory testing procedures (Two-Point Discrimination, Mechanical Detection Threshold and Pressure Pain Threshold). RESULTS: Patients who reported lower Pressure Pain Threshold or Mechanical Detection Threshold, higher acuity for Two Point Discrimination, and higher than average sensory avoiding and sensory sensitivity patterns were less adherent with garment wear. CONCLUSIONS: Overall, sensory factors assessed using both self-report and quantitative sensory testing were associated with compression garment adherence. This knowledge suggests the value in developing and evaluating sensory-informed treatment strategies to improve compression garment wear.

A qualitative exploration of South African men's perceived effects of Androgen Deprivation Therapy (ADT) as a treatment for advanced prostate cancer.

OBJECTIVE: We undertake qualitative research with men treated in a Pretoria, South Africa Oncology clinic to address men's self-reported experiences on androgen deprivation therapy (ADT). METHODS: Analyses rely upon 22 men's responses to open-ended questions during interviews. These men were 63-78 years of age, and almost all married (three widowed), had children and were no longer engaged in paid work. RESULTS: In addressing questions about the anticipated and experienced positive and broader side effects of ADT, men referred to its treatment for prostate cancer, with several generally specifying health or life. Patients also referred to a variety of more specific effects such as pain, nausea, difficulties urinating, gaining weight, low energy and sleep disruptions that appeared to reflect a mixture of influences of prostate cancer, ADT and oncological treatment. In addressing a question about the effects of ADT on romantic/sex life, 16 of 19 married men referred to deleterious impacts on their sex lives. With respect to perceived family, work or broader social life impacts, some men noted others' worries and social support. CONCLUSION: Findings are situated within discussions of existing research on ADT largely from North American or European samples, and broader views of testosterone and male social behavior.

Non-adherence with compression garment wear in adult burns patients: A systematic review and meta-ethnography.

OBJECTIVE: Up to 40% of adult burn-injured patients are non-adherent with prescribed compression garment wear. The aim of this paper is to systematically review the literature to understand barriers to adherence with compression garment wear. METHOD: Papers were included if they: investigated adults who required compression garment wear for the management of burns scars; focussed on reasons for non-adherence to compression garment wear; and were available in English. The process of meta-ethnography was then followed to synthesise the findings. RESULTS: The factors impacting adherence to compression garment wear were grouped into six themes: sensory factors, psychological state, the impact of the garment on the patient's function, the availability of social support, the degree of choice, and the education provided to patients by their therapists. A model of compression garment adherence was developed detailing how these factors fit within the continuum of treatment for a burn-injured patient. CONCLUSIONS: Adherence to compression garment wear post-burn injury is a complex, dynamic phenomenon impacted by a range of factors. Findings from this review may inform approaches to support more consistent and/or extended garment wear, potentially improving scar outcomes and quality-of-life. Further research is recommended to investigate how each of the six identified themes impact adherence.

Embedded research: a promising way to create evidence-informed impact in public health?

Background: Embedded research (ER) is recognized as one way to strengthen the integration of evidence into public health (PH) practice. In this paper, we outline a promising example of the co-production of research evidence between Fuse, the UKCRC Centre for Translational Research in Public Health and a local authority (LA) in north east England. Methods: We critically examine attempts to share and use research findings to influence decision-making in a LA setting, drawing on insights from PH practitioners, managers, commissioners and academic partners involved in this organizational case study. We highlight what can be achieved as a co-located embedded researcher. Results: The benefits and risks of ER are explored, alongside our reflections on the added value of this approach and the institutional prerequisites necessary for it to work. We argue that while this is not a new methodological approach, its application in PH as a way to facilitate evidence use is novel, and raises pragmatic and theoretical questions about the nature of impact and the extent to which it can be engineered. Conclusion: With increased situated understanding of organizational culture and norms and greater awareness of the socio-political realities of PH, ER enables new co-produced solutions to become possible.

Behaviour of 4- to 5-year-old nondisabled ELBW children: Outcomes following group-based physiotherapy intervention.

BACKGROUND: Extreme prematurity or extremely low birth weight (ELBW) can adversely affect behaviour. Nondisabled ELBW children are at risk of behavioural problems, which may become a particular concern after commencement of formal education. This study explored the frequency of behavioural and emotional problems amongst nondisabled ELBW children at 4 to 5 years of age and whether intervention had a positive influence on behaviour. The relationship between behaviour, gender, and other areas of performance at 5 years was explored. METHODS: Fifty 4-year-old children (born <28 weeks gestation or birth weight <1,000 g) with minimal/mild motor impairment were randomly allocated to intervention (n = 24) or standard care (n = 26). Intervention was 6 group-based physiotherapy weekly sessions and home programme. Standard care was best practice advice. The Child Behavior Checklist (CBCL) for preschool children was completed at baseline and at 1-year post-baseline. Other measures at follow-up included Movement Assessment Battery for Children Second Edition, Beery Visual-Motor Integration Test 5th Edition, and Peabody Picture Vocabulary Test 4th Edition. RESULTS: The whole cohort improved on CBCL total problems score between baseline (mean 50.0, SD 11.1) and 1-year follow-up (mean 45.2, SD 10.3), p = .004. There were no significant differences between groups over time on CBCL internalizing, externalizing, or total problems scores. The intervention group showed a mean difference in total problems score of -3.8 (CI [1.5, 9.1]) between times, with standard care group values being -4.4 (CI [1.6, 7.1]). Males had higher total problems scores than females (p = .026), although still performed within the "normal" range. CBCL scores did not correlate with other scores. CONCLUSIONS: The behaviour of nondisabled ELBW children was within the "normal" range at 4 to 5 years, and both intervention and standard care may have contributed to improved behavioural outcomes. Behaviour was not related to performance in other developmental domains.

CRIPTO and its signaling partner GRP78 drive the metastatic phenotype in human osteotropic prostate cancer.

CRIPTO (CR-1, TDGF1) is a cell surface/secreted oncoprotein actively involved in development and cancer. Here, we report that high expression of CRIPTO correlates with poor survival in stratified risk groups of prostate cancer (PCa) patients. CRIPTO and its signaling partner glucose-regulated protein 78 (GRP78) are highly expressed in PCa metastases and display higher levels in the metastatic ALDHhigh sub-population of PC-3M-Pro4Luc2 PCa cells compared with non-metastatic ALDHlow. Coculture of the osteotropic PC-3M-Pro4Luc2 PCa cells with differentiated primary human osteoblasts induced CRIPTO and GRP78 expression in cancer cells and increases the size of the ALDHhigh sub-population. Additionally, CRIPTO or GRP78 knockdown decreases proliferation, migration, clonogenicity and the size of the metastasis-initiating ALDHhigh sub-population. CRIPTO knockdown reduces the invasion of PC-3M-Pro4Luc2 cells in zebrafish and inhibits bone metastasis in a preclinical mouse model. These results highlight a functional role for CRIPTO and GRP78 in PCa metastasis and suggest that targeting CRIPTO/GRP78 signaling may have significant therapeutic potential.

Tumor microenvironment heterogeneity: challenges and opportunities.

The tumor microenvironment (TME) has been recognized as an integral component of malignancies in breast and prostate tissues, contributing in confounding ways to tumor progression, metastasis, therapy resistance and disease recurrence. Major components of the TME are immune cells, fibroblasts, pericytes, endothelial cells, mesenchymal stroma/stem cells (MSCs), and extracellular matrix (ECM) components. Herein, we discuss the molecular and cellular heterogeneity within the TME and how this presents unique challenges and opportunities for treating breast and prostate cancers.

Activin A/BMP2 chimera AB235 drives efficient redifferentiation of long term cultured autologous chondrocytes.

Autologous chondrocyte implantation (ACI) depends on the quality and quantity of implanted cells and is hindered by the fact that chondrocytes cultured for long periods of time undergo dedifferentiation. Here we have developed a reproducible and efficient chondrogenic protocol to redifferentiate chondrocytes isolated from osteoarthritis (OA) patients. We used morphological, histological and immunological analysis together with a RT-PCR detection of collagen I and collagen II gene expression to show that chondrocytes isolated from articular cartilage biopsies of patients and subjected to long-term culture undergo dedifferentiation and that these cells can be redifferentiated following treatment with the chimeric Activin A/BMP2 ligand AB235. Examination of AB235-treated cell pellets in both in vitro and in vivo experiments revealed that redifferentiated chondrocytes synthesized a cartilage-specific extracellular matrix (ECM), primarily consisting of vertically-orientated collagen fibres and cartilage-specific proteoglycans. AB235-treated cell pellets also integrated into the surrounding subcutaneous tissue following transplantation in mice as demonstrated by their dramatic increase in size while non-treated control pellets disintegrated upon transplantation. Thus, our findings describe an effective protocol for the promotion of redifferentiation of autologous chondrocytes obtained from OA patients and the formation of a cartilage-like ECM that can integrate into the surrounding tissue in vivo.

The Effect of Fish Oil, Vitamin D and Protein on URTI Incidence in Young Active People.

Upper respiratory tract infections (URTI) are a frequent illness among athletes. We investigated the effect of a multi-nutrient supplement (vitamin D, fish oil and protein) on the occurrence of URTI in young active people. 42 young recreational athletes were randomly assigned to receive either supplementation (550 mg DHA, 550 mg EPA, 10 µg vitamin D3 and 8 g whey protein) or placebo for 16 weeks. Unstimulated saliva samples were collected by passive drool. Samples were analysed for IgA (sIgA) concentration and the secretion rate extrapolated by multiplying concentration by saliva flow rate. Physical activity levels and URTI incidence were monitored by questionnaire. Training status was not different between the 2 groups. There were no differences in the incidence, severity and duration of URTI. However the number of symptom days was lower in the supplemented compared to the control group (1.72±1.67 vs. 2.79±1.76; P<0.05). sIgA concentration and secretion rate did not differ between groups. This study demonstrates that 16 weeks of supplementation with fish oil, vitamin D and protein did not modify the incidence, severity and duration of URTI, although the total number of symptom days was reduced, in a healthy active population.

A novel intronic splice site deletion of the IL-2 receptor common gamma chain results in expression of a dysfunctional protein and T-cell-positive X-linked Severe combined immunodeficiency.

X-linked severe combined immunodeficiency is caused by mutations in the IL-2 receptor common gamma chain and classically presents in the first 6 months of life with predisposition to bacterial, viral and fungal infections. In most instances, affected individuals are lymphopenic with near complete absence of T cells and NK cells. We report a boy who presented at 12 months of age with Pneumocystis jiroveci pneumonia and a family history consistent with X-linked recessive inheritance. He had a normal lymphocyte count including the presence of T cells and a broad T-cell-receptor diversity, as well as normal surface expression of the common gamma chain (CD132) protein. He however had profound hypogammaglobulinaemia, and IL-2-induced STAT5 phosphorylation was absent. Sequencing of IL-2RG demonstrated a 12-base pair intronic deletion close to the canonical splice site of exon 5, which resulted in a variety of truncated IL2RG mRNA species. A review of the literature identified 4 other patients with T-cell-positive X-SCID, with the current patient being the first associated with an mRNA splicing defect. This case raises the question of how a dysfunctional protein incapable of mediating STAT5 phosphorylation might nonetheless support T-cell development. Possible explanations are that STAT5-mediated signal transduction may be less relevant to IL7-receptor-mediated T-cell development than are other IL7R-induced intracellular transduction pathways or that a low level of STAT5 phosphorylation, undetectable in the laboratory, may be sufficient to support some T-cell development.

Systems Epidemiology: What's in a Name?

Systems biology is an interdisciplinary effort to integrate molecular, cellular, tissue, organ, and organism levels of function into computational models that facilitate the identification of general principles. Systems medicine adds a disease focus. Systems epidemiology adds yet another level consisting of antecedents that might contribute to the disease process in populations. In etiologic and prevention research, systems-type thinking about multiple levels of causation will allow epidemiologists to identify contributors to disease at multiple levels as well as their interactions. In public health, systems epidemiology will contribute to the improvement of syndromic surveillance methods. We encourage the creation of computational simulation models that integrate information about disease etiology, pathogenetic data, and the expertise of investigators from different disciplines.

Proton beam therapy and localised prostate cancer: current status and controversies.

Proton therapy is a promising, but costly, treatment for prostate cancer. Theoretical physical advantages exist; yet to date, it has been shown only to be comparably safe and effective when compared with the alternatives and not necessarily superior. If clinically meaningful benefits do exist for patients, more rigorous study will be needed to detect them and society will require this to justify the investment of time and money. New technical advances in proton beam delivery coupled with shortened overall treatment times and declining device costs have the potential to make this a more cost-effective therapy in the years ahead.

Fos-activation of FoxP2 and Lmx1b neurons in the parabrachial nucleus evoked by hypotension and hypertension in conscious rats.

The parabrachial nucleus (PB) is a brainstem cell group that receives a strong input from the nucleus tractus solitarius regarding the physiological status of the internal organs and sends efferent projections throughout the forebrain. Since the neuroanatomical organization of the PB remains unclear, our first step was to use specific antibodies against two neural lineage transcription factors: Forkhead box protein2 (FoxP2) and LIM homeodomain transcription factor 1 beta (Lmx1b) to define the PB in adult rats. This allowed us to construct a cytoarchitectonic PB map based on the distribution of neurons that constitutively express these two transcription factors. Second, the in situ hybridization method combined with immunohistochemistry demonstrated that mRNA for glutamate vesicular transporter Vglut2 (Slc17a6) was present in most of the Lmx1b+ and FoxP2+ parabrachial neurons, indicating these neurons use glutamate as a transmitter. Third, conscious rats were maintained in a hypotensive or hypertensive state for 2h, and then, their brainstems were prepared by the standard c-Fos method which is a measure of neuronal activity. Both hypotension and hypertension resulted in c-Fos activation of Lmx1b+ neurons in the external lateral-outer subdivision of the PB (PBel-outer). Hypotension, but not hypertension, caused c-Fos activity in the FoxP2+ neurons of the central lateral PB (PBcl) subnucleus. The Kölliker-Fuse nucleus as well as the lateral crescent PB and rostral-most part of the PBcl contain neurons that co-express FoxP2+ and Lmx1b+, but none of these were activated after blood pressure changes. Salt-sensitive FoxP2 neurons in the pre-locus coeruleus and PBel-inner were not c-Fos activated following blood pressure changes. In summary, the present study shows that the PBel-outer and PBcl subnuclei originate from two different neural progenitors, contain glutamatergic neurons, and are affected by blood pressure changes, with the PBel-outer reacting to both hypo- and hypertension, and the PBcl signaling only hypotensive changes.

Is Roifman syndrome an X-linked ciliopathy with humoral immunodeficiency? Evidence from 2 new cases.

Roifman syndrome is a rare syndrome of bone dysplasia, growth retardation, retinal dystrophy and humeral immunodeficiency. Six cases have been reported to date, all of whom are male. We report a boy with clinical features of Roifman syndrome, whose older sister has skewed X-inactivation and a milder phenotype of the same disorder, supporting the hypothesis that this is an X-linked recessive condition. Both children had previously had a provisional diagnosis of Jeune dysplasia, and the boy had neonatal hip X-rays which demonstrated 'acetabular spurs' which are seen in a number of diseases thought to be caused by dysfunction of nonmotile cilia, including Jeune asphyxiating thoracic dystrophy. This finding in combination with other features such as retinal dystrophy, hepatic and renal disease suggests that the gene which is affected in Roifman syndrome may be involved with the function of nonmotile cilia and that Roifman syndrome may be the first example of a ciliopathy with associated immunodeficiency.

Unusual and severe lesions of proventricular dilatation disease in cockatiels (Nymphicus hollandicus) acting as healthy carriers of avian bornavirus (ABV) and subsequently infected with a virulent strain of ABV.

A flock of 14 apparently healthy cockatiels, purchased from a single aviary, was tested for the presence of avian bornavirus (ABV). Twelve birds were found to be intermittently shedding ABV, predominantly genotype 4. Four of the cockatiels known to be shedding ABV4 were subsequently challenged with the tissue culture derived, virulent M24 strain of ABV4. The challenged birds remained in apparent good health until day 92 when one was found dead. The remaining three birds began to exhibit severe neurologic signs, ataxia and convulsions on day 110 and were euthanized. On necropsy, all four birds showed mild proventricular enlargement. In contrast, histopathological examination showed unusually severe and widespread tissue lesions. These included massive lymphocytic infiltration and lymphoid nodule formation within and around the ganglia throughout the gastrointestinal tract. There were similar lesions in the medullary cords of the adrenal gland, heart, spleen, liver, kidney, lungs, pancreas, testes and ovary. Immunohistochemistry demonstrated ABV P antigen not only in the cells of the central and autonomic nervous systems, but also within the mononuclear cells infiltrating the various organs. Two healthy cockatiels, one of which was a known ABV carrier, were inoculated with uninfected tissue culture cells and euthanized on day 150. These birds showed no gross lesions of proventricular dilatation disease but had a mild lymphocytic infiltration in their liver, spleen, and kidneys. Prior infection with ABV did not therefore confer significant immunity on these birds, and may have resulted in increased disease severity following challenge.