After CNS injury, axon regeneration is blocked by an inhibitory environment consisting of the highly upregulated tenascin-C and chondroitin sulfate proteoglycans (CSPGs). Tenascin-C promotes growth ...of axons if they express a tenascin-binding integrin, particularly α9β1. Additionally, integrins can be inactivated by CSPGs, and this inhibition can be overcome by the presence of a β1-binding integrin activator, kindlin-1. We examined the synergistic effect of α9 integrin and kindlin-1 on sensory axon regeneration in adult rat spinal cord after dorsal root crush and adeno-associated virus transgene expression in dorsal root ganglia. After 12 weeks, axons from C6-C7 dorsal root ganglia regenerated through the tenascin-C-rich dorsal root entry zone into the dorsal column up to C1 level and above (>25 mm axon length) through a normal pathway. Animals also showed anatomical and electrophysiological evidence of reconnection to the dorsal horn and behavioral recovery in mechanical pressure, thermal pain, and ladder-walking tasks. Expression of α9 integrin or kindlin-1 alone promoted much less regeneration and recovery.
The study demonstrates that long-distance sensory axon regeneration over a normal pathway and with sensory and sensory-motor recovery can be achieved. This was achieved by expressing an integrin that recognizes tenascin-C, one of the components of glial scar tissue, and an integrin activator. This enabled extensive long-distance (>25 mm) regeneration of both myelinated and unmyelinated sensory axons with topographically correct connections in the spinal cord. The extent of growth and recovery we have seen would probably be clinically significant. Restoration of sensation to hands, perineum, and genitalia would be a significant improvement for a spinal cord-injured patient.
Summary
Background
All organ transplant populations are predisposed to increased rates of keratinocyte carcinoma (KC). Since this increased risk was first appreciated, immunosuppressive regimens have ...changed and organ transplant recipients (OTRs) have been aggressively screened for KC. There is a perception that these measures have impacted on KC incidence but there is a paucity of population‐based studies on post‐transplant rates of basal cell carcinoma (BCC).
Objectives
To identify trends in incidence rates for KC following solid organ transplantation over the past two decades.
Methods
This nationwide, population‐based study included all solid OTRs transplanted between 1994 and 2014. Patient data were matched to national cancer registry data to determine the standardized incidence ratio (SIR) of KC in solid OTRs compared with the general population.
Results
In total 3580 solid OTRs were included. The total follow‐up time was 28 407 person‐years (median follow‐up 7·11 years). The overall SIRs for squamous cell carcinoma (SCC) and BCC were 19·7 and 7·0, respectively. Our study documents a progressive fall in the SIRs for SCC and BCC from peak SIRs (95% confidence intervals) in 1994–1996 of 26·4 (21·5–32·4) and 9·1 (7·4–11·3) to 6·3 (2·3–16·7) and 3·2 (1·4–7·1) in 2012–2014, respectively. The ratio of SCC to BCC has remained at 3 to 1 over the last two decades.
Conclusions
Our study is the first to demonstrate a significant reduction over the past two decades in the incidences of both SCC and BCC following solid organ transplantation. The SCC‐to‐BCC ratio was maintained, demonstrating that both are reducing equally. This trend coincided with temporal changes in immunosuppressive protocols and the introduction of skin cancer prevention programmes.
What's already known about this topic?
Prior studies have shown that the risk of cutaneous squamous cell carcinoma (SCC) has declined over recent decades following solid organ transplantation.
It is not known whether the risk of basal cell carcinoma (BCC) has reduced in line with this.
What does this study add?
Our study documents a progressive fall in the risk of SCC and BCC following solid organ transplantation over the last two decades.
The SCC‐to‐BCC ratio was maintained, demonstrating that both are reducing equally.
The trends observed in our study coincided with temporal changes in immunosuppressive protocols and the introduction of cancer prevention programmes, suggesting that these factors have positively impacted on the risk of keratinocyte carcinoma in this cohort.
Linked Editorial: Gjersvik. Br J Dermatol 2019; 181:879–880
Plain language summary available online
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This study was commissioned to assess if there are regional differences in the acceptability of beef between consumers from Northern Ireland (NI), Republic of Ireland (ROI) and Great Britain (GB). ...Palatability traits were affected by socioeconomic and behavioural factors such as preferred cooking endpoint, animal welfare, value, health aspects of beef product, ease of preparation as well as consumption frequency for specific cuts. “Willingness to pay” (WTP) was influenced by income, preferred cooking endpoint, value of beef product, ease of preparation and consumption frequency for frying steak.
Results showed that GB consumers scored higher for the same striploin steak compared to NI and ROI consumers. This may be due to differences in the motivation for beef choice and/or consumption habits. GB consumers were less concerned about the healthiness of beef product and beef origin. In addition, a higher consumption frequency for rump was reported in GB, which may explain the higher sensory scores observed among GB consumers for striploins.
Autism spectrum disorder (ASD) is a developmental disorder characterised by deficits in social interactions and communication, with stereotypical and repetitive behaviours. Recent evidence suggests ...that maternal immune dysregulation may predispose offspring to ASD. Independent samples t-tests revealed downregulation of IL-17A concentrations in cases, when compared to controls, at both 15 weeks (p = 0.02), and 20 weeks (p = 0.02), which persisted at 20 weeks following adjustment for confounding variables. This adds to the growing body of evidence that maternal immune regulation may play a role in foetal neurodevelopment.
Notch receptors function in highly conserved intercellular signalling pathways that direct cell-fate decisions, proliferation and apoptosis in metazoans. Fringe proteins can positively and negatively ...modulate the ability of Notch ligands to activate the Notch receptor. Here we establish the biochemical mechanism of Fringe action. Drosophila and mammalian Fringe proteins possess a fucose-specific beta1,3 N-acetylglucosaminyltransferase activity that initiates elongation of O-linked fucose residues attached to epidermal growth factor-like sequence repeats of Notch. We obtained biological evidence that Fringe-dependent elongation of O-linked fucose on Notch modulates Notch signalling by using co-culture assays in mammalian cells and by expression of an enzymatically inactive Fringe mutant in Drosophila. The post-translational modification of Notch by Fringe represents a striking example of modulation of a signalling event by differential receptor glycosylation and identifies a mechanism that is likely to be relevant to other signalling pathways.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The effect of supplementation of beef cattle diets with tea catechins (TC) (1000
mg/animal/day) and rosemary extract (RE) (1000
mg/animal/day), for 103 days preceding slaughter, on the oxidative ...stability of
M. longissimus dorsi (LD) steaks was evaluated. Dietary supplementation with TC and RE did not increase plasma total antioxidant status (TAS), LD α-tocopherol concentrations or pH. In LD steaks stored aerobically or in modified atmosphere packs (80% O
2:20% CO
2) (MAP) for up to 8 days at 4
°C, surface redness (CIE ‘
a’ redness value) and lipid stability (TBARS, mg MDA (malondialdehyde)/kg muscle) were not significantly improved as a result of supplementation with TC and RE. Similarly no improvement in the sensory properties and lipid stability of cooked LD slices, stored aerobically or in 30% CO
2:70% N
2 for up to 11 days at 4
°C, was observed. An in vitro fermentation study demonstrated that TC and RE were not fermented to any great extent under simulated rumen conditions. Direct addition of TC (1000
ppm) and RE (1000
ppm) significantly (
P
<
0.05) improved the colour and lipid stability in LD patties stored in 80% O
2:20% CO
2 for up to 8 days at 4
°C, thus, demonstrating the antioxidant potential of TC and RE supplements employed in the present study.
To assess the utility of a volumetric low-dose computed tomography (CT) thorax (LDCTT) protocol at a dose equivalent to a posteroanterior (PA) and lateral chest radiograph for surveillance of cystic ...fibrosis (CF) patients.
A prospective study was undertaken of 19 adult patients with CF that proceeded to LDCTT at 12 and 24 months following initiation of ivacaftor. A previously validated seven-section, low-dose axial CT protocol was used for the 12-month study. A volumetric LDCTT protocol was developed for the 24-month study and reconstructed with hybrid iterative reconstruction (LD-ASIR) and pure iterative reconstruction (model-based IR LD-MBIR). Radiation dose was recorded for each scan. Image quality was assessed quantitatively and qualitatively, and disease severity was assessed using a modified Bhalla score. Statistical analysis was performed and p-values of <0.05 were considered statistically significant.
Volumetric LD-MBIR studies were acquired at a lower radiation dose than the seven-section studies (0.08 ± 0.01 versus 0.10 ± 0.02 mSv; p=0.02). LD-MBIR and seven-section ASIR images had significantly lower levels of image noise compared with LD-ASIR images (p<0.0001). Diagnostic acceptability scores and depiction of bronchovascular structures were found to be acceptable for axial and coronal LD-MBIR images. LD-MBIR images were superior to LD-ASIR images for all qualitative parameters assessed (p<0.0001). No significant change was observed in mean Bhalla score between 1-year and 2-year studies (p=0.84).
The use of a volumetric LDCTT protocol (reconstructed with pure IR) enabled acquisition of diagnostic quality CT images, which were considered extremely useful for surveillance of CF patients, at a dose equivalent to a PA and lateral chest radiograph.
•CF may be evaluated with CT at a radiation dose equivalent to a chest radiograph.•Low dose thoracic CT may be acquired with a mean ED of 0.08 ± 0.01mSv.•Compared with ASIR, MBIR images demonstrate superior objective image parameters.
Summary
Age-specific and age-standardized associations between socioeconomic status (SES) and fractures in adults showed a social gradient of fracture, irrespective of fracture site. Compared to the ...highest SES, males in the lowest SES group had a sixfold increased odds for any fracture, whilst females had a twofold increased odds.
Introduction
The effective identification of predisposing risk factors for fracture requires understanding any association with SES. These investigations should consider both sexes, span the adult age range and include any fractures. We investigated age- and sex-specific and age-standardized associations between SES and fractures at any skeletal site in Australians aged ≥50 years.
Methods
Incident fractures that occurred 2006–2007 for adults aged ≥50 years were identified from radiological reports extracted for the Barwon Statistical Division, in south-eastern Australia. SES was determined by cross-referencing residential addresses with Australian Bureau of Statistics census data and then categorized in quintiles. We compared frequencies of observed vs. expected fractures for SES quintiles using
χ
2
comparison, calculated age-specific fracture incidence across SES and compared age-standardized fracture rates in SES quintile 1 to quintile 5.
Results
We identified 3943 incident fractures (69.4 % female); 47.4 % had occurred at major osteoporotic fracture (MOF) sites (hip, humerus, spine and forearm/wrist). Differences existed in observed vs. expected fractures across SES quintiles (
p
≤ 0.001, sexes combined); all fractures showed an inverse association with SES (
p
≤ 0.001, sexes combined). Compared to the highest SES quintile, individuals from the lowest SES quintile had between two to six times greater standardized fracture rates.
Conclusions
Disadvantaged men and women have an increased fracture incidence compared to their less disadvantaged counterparts. The large differences in fracture rates between SES groups warrant further research into designing appropriate, targeted interventions for those demographics at most risk.
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