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Background: The Cancer Research UK Cancer Awareness Measure Survey (2022) found older age as a risk factor for cancer to be low (around 2-4% across UK nations). However, 89 in 100 cancers are in those aged 50 years and older, and the majority of health-communications are targeted to these higher risk groups. This research aimed to understand the potential impact on health behaviours of communicating messages on relative increased risk of cancer with older age on participant's capability, motivation, and opportunity (COM-B model) in relation to positive early diagnosis health behaviours (body vigilance, intention to take part in cancer screening, preventative measures)., Methods: In this qualitative study, we conducted 60 min semi-structured paired-depth interviews of people aged 25-74 years from across the UK (20 pairs; n=40; age: mean 58·5 years, range 25-74; 19 [47%] men and 21 [53%] women; 27 [67%] White and 13 [33%] from Black or Asian minority ethnic groups). Participants were recruited via a recruitment agency and provided with an incentive of £60 for their time. To assess potential longer-term impact, participants filled a survey 2 weeks later on their views on the messages tested, and on self-reported actions taken as a result of the messages tested. The three different messages tested were rotated. Data were analysed using rapid thematic techniques, two moderators reviewed the data, and a framework analysis style assessed themes against capability, opportunity, and motivation (COM-B model)., Findings: Message 2 was the most preferred, as it was clear and easy to understand. Results suggested that including this messaging in health campaigns could encourage some positive early diagnosis heath behaviours. The post survey identified self-reported behaviour changes in nine (23%) of the 40 participants and sustained intentions in 29 (73%). Results overlayed with COM-B, identified messaging could support behaviour change by increasing awareness (psychological capability), providing a social cue (social opportunity), and encouraging emotions related to not wanting to get cancer or that they should be doing specific behaviours (reflective motivation)., Interpretation: Findings suggest communicating this message might have a positive effect on help-seeking behaviours in older adults (age ≥50 years). However, considerations include ensuring that the message is clear and understandable and that it doesn't induce fear. Although this study design allowed for more in-depth exploration, results are limited due to the small sample size., Funding: Cancer Research UK., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Cancer Research UK ran a mass-media campaign for 6 weeks from Sept 1, 2022, to Sept 13, 2022, targeted to people aged 50 years and older and from a lower social-grade (C2DE) in Northern Ireland. The campaign was developed to target barriers to help-seeking for the target audience. With this evaluation, we aimed to compare reported barriers and self-reported help-seeking before and after the campaign to assess changes potentially related to the campaign., Methods: We ran cross-sectional surveys that collected data from independent participants before the campaign (wave 1; n=1262; July 18-Aug 31, 2022) and after the campaign (wave 2; n=1250; Oct 3-Nov 3, 2022; N=2512). A recruitment agency recruited participants to be representative of Northern Ireland by age, gender, and social grade (Office for National Statistics, 2011; quota sampling). After wave 2, age range was 16-94 years (mean 51 years) and gender breakdown was 46% male (n=1152), 54% female (n=1356), and <1% other (n=3). Participants gave written informed consent, and the survey was administered using Computer Assisted Personal Interviewing (CAPI) at waves 1 and 2, and Computer Assisted Telephone Interviewing (CATI) at wave 1. Ethics approval was given by Queens University Belfast. Data were analysed in SPSS., Findings: 78% of the targeted audience (354/451) reported remembering the TV campaign. Of people who reported no symptoms, more reported "nothing would put them off or delay seeking medical attention" at wave 2 (447 [41%] of 1084 participants) than at wave 1 (221 [24%] of 936 participants), and this difference was significant (t(939.796)=2·243, p=0·025; 95% CI 0·083 to 1·244). Participants who reported experiencing a symptom (wave 1 n=186; wave 2 103) were less likely to report that they did not seek help from their GP or doctor in wave 2 (n=63 [61%]) than in wave 1 (n=157 [85%]); however, this difference was not significant (t(214.167)=1·133, p=0·258, 95% CI -0·051 to 0·188)., Interpretation: Decreases in barriers reported "nothing putting them off seeking help" and decreases in not seeking help from a GP or doctor to help seeking for actual symptoms experienced suggests this campaign might have resulted in some positive shifts in self-reported help-seeking behaviours for actual symptoms. However, these findings should be interpreted in light of the limitations of this research. Although this was a large sample, additional consideration should be given to the use of independent samples (rather than repeated surveys with the same population), self-reported data, and different data collection methods., Funding: Community Foundation for Northern Ireland through the Department of Health Cancer Charities Fund., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: 'Overweight and obesity' is the second biggest preventable cause of cancer after smoking. In 2018, Cancer Research UK launched an awareness raising campaign about the link between overweight and obesity and cancer risk. This study aimed to evaluate the reach and impact of the campaign., Study Design: This study was a repeated cross-sectional online survey., Methods: The campaign consisted of six elements including the main message that 'Obesity is a cause of cancer'. UK adults and Members of Parliament (MPs) were surveyed before the campaign (W1; n = 2124 and n = 151), 1 month (W2; n = 2050 and n = 151) and 3 months after the campaign (W3; n = 2059 and MPs not surveyed). Outcome measures were campaign reach, awareness of overweight and obesity as risk factors for cancer, attitudes towards individuals who are overweight or obese, support for policies to reduce obesity and reactions to the campaign., Results: Overall, 76.2% of MPs and just under half of the public (47.5% in W2 and 36.8% in W3) reported having seen the campaign. Unprompted awareness of obesity as a risk factor increased among the public from 17.1% at W1 to 43.3% in W2 (odds ratio 3.71, 95% confidence interval 3.18-4.33) and 30.3% in W3 (odds ratio 2.11, 95% confidence interval 1.80-2.47). A similar pattern was seen for prompted awareness and among MPs. There were no consistent changes in attitudes towards overweight individuals or support for policies to reduce obesity., Conclusions: This evaluation suggests that the campaign achieved the primary objective of increasing awareness of the link between obesity and cancer without increasing negative attitudes towards individuals who are overweight or obese., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Despite growing evidence that e-cigarettes are likely less harmful than cigarettes, perceptions of equal or more harm have increased worldwide. This study aimed to identify the most common reasons behind adults' perceptions of the (i) relative harm of e-cigarettes compared with cigarettes and (ii) effectiveness of e-cigarettes for smoking cessation., Methods: Adults (N = 1646) from Northern England were recruited through online panels from December-March 2017/2018, using quota sampling to guarantee socio-demographic representativeness. Qualitative content analysis of open-ended responses was performed with codes representing reasons for a given perception about e-cigarettes. Percentages of participants who gave each reason for each perception were calculated., Results: 823 (49.9%) participants agreed that e-cigarettes were less harmful than cigarettes, 283 (17.1%) disagreed, and 540 (32.8%) were undecided. The most common reasons for agreeing that e-cigarettes were less harmful than cigarettes were that they produce no smoke (29.8%) and fewer toxins (28.9%). Those who disagreed were most concerned about a perceived lack of trustworthy research (23.7%) and safety issues (20.8%). Lacking knowledge (50.4%) was the most common reason for being undecided. 815 (49.5%) of participants agreed that e-cigarettes were an effective smoking cessation aid, 216 (13.2%) disagreed, and 615 (37.4%) were undecided. The most common reasons participants gave for agreeing were related to e-cigarettes being successful smoking replacements (50.3%) and advice from family, friends or health professionals (20.0%). Respondents who disagreed were most concerned about e-cigarettes being addictive (34.3%) and containing nicotine (15.3%). Lacking knowledge (45.2%) was the most common reason for being undecided., Conclusions: Negative perceptions of e-cigarette harm were driven by concerns about a perceived lack of research and safety issues. Adults who viewed e-cigarettes as ineffective for smoking cessation feared that they perpetuate nicotine addiction. Campaigns and guidelines that address these concerns may help promote informed perceptions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Recent studies suggest that the soluble N-ethylmaleimide-sensitive factor attached protein (SNAP) receptor (SNARE)-mediated membrane fusion system is involved in vesicle fusion in the plasma membrane that allows expansion for neurite elongation. There have been several reports analyzing the effects of neurite outgrowth by inhibition of SNAREs. In this study, we took the opposite approach by overexpressing green fluorescent protein (GFP)-fusion SNAREs, including VAMP-2, SNAP-25A, and syntaxin1A, in PC12 cells to investigate the role of SNAREs in the neurite outgrowth of PC12 cells. Neurite outgrowth analysis demonstrated that: (1) GFP-VAMP-2 increased the length of individual neurites, without changing the number of neurites per cell; (2) GFP-SNAP-25A increased the number of neurites per cell, with no change in the length of the individual neurites. In both cases, the total length of neurites per cell was increased; (3) GFP-syntaxin1A resulted in no significant change, either in neurite length, or in the number of neurites per cell. These findings suggest that when overexpressed in PC12 cells, VAMP-2 can promote neurite elongation, while SNAP-25A can stimulate neurite sprouting. On the other hand, overexpression of syntaxin1A neither promotes nor inhibits neurite outgrowth. Thus VAMP-2 and SNAP-25A play different roles in neurite elongation and sprouting.

Excimer laser (KrF excimer laser, 248 nm wavelength) was used to damage cellular components in the dorsal funiculus at the lumbar level (L2) of the rat spinal cord. An open lesion was not found at the irradiation site on the spinal cord. However, the cytological examination revealed that cellular components were damaged to the depth of 200-500 microm from the pial surface. The characteristic feature was that at the border of the lesion, many axons remained naked but intact after their myelin sheaths had been completely disintegrated. Such naked axons were subsequently remyelinated by mature or immature glial cells. Mature oligodendrocytes, while retaining their cytoplasmic processes connected with the myelin sheaths of unaffected axons, extended new cytoplasmic processes on nearby naked axons and made new myelin sheaths around them. In contrast, 7 days after the irradiation, numerous immature glial cells appeared in association with naked axons, and some of them were differentiated into oligodendrocytes forming thin myelin sheaths on naked axons. These findings suggest that demyelinated axons can cause the proliferation and probably dedifferentiation of the oligodendrocyte lineage. The use of lasers provides a unique experimental model of demyelination and remyelination in the central nervous system of adult mammals.

Peripheral nerve regeneration comprises the formation of axonal sprouts, their outgrowth as regenerating axons and the reinnervation of original targets. This review focuses on the morphological features of axonal sprouts at the node of Ranvier and their subsequent outgrowth guided by Schwann cells or by Schwann cell basal laminae. Adhesion molecules such as N-CAM, L1 and N-cadherin are involved in the axon-to-axon and axon-to-Schwann cell attachment, and it is suggested that integrins such as alpha 1 beta 1 and alpha 6 beta 1 mediate the attachment between axons and Schwann cell basal laminae. The presence of synaptic vesicle-associated proteins such as synaptophysin, synaptotagmin and synapsin I in the growth cones of regenerating axons indicates the possibility that exocytotic fusion of vesicles with the surface axolemma supplies the membranous components for the extension of regenerating axons. Almost all the subtypes of protein kinase C have been localized in growth cones both in vivo and in vitro. Protein kinase C and GAP-43 are implicated to be involved in at least some part of the adhesion of growth cones to the substrate and their growth activity. The significance of tyrosine kinase in growth cones is emphasized. Tyrosine kinase plays an important role in intracellular signal transduction of the growth of regenerating axons mediated by both nerve trophic factors and adhesion molecules. Growth factors such as NGF, BDNF, CNTF and bFGF are also discussed mainly in terms of the influence of Schwann cells on regenerating axons.

Rabphilin-3A is a putative target protein for Rab3A small GTP-binding protein which is implicated in neurotransmitter release. Rabphilin-3A is expressed mainly in brain, but its subcellular localization remains to be clarified. Immunohistochemical analysis has revealed that Rabphilin-3A is most abundant in the synaptic area of the rat cerebellum, retina, and neuromuscular junction. Ultrastructural analysis of the neuromuscular junction using the immunogold method indicates that Rabphilin-3A is localized on the synaptic vesicle. Subcellular fractionation analysis of rat brain has shown that Rabphilin-3A is most highly concentrated in the purified synaptic vesicle fraction. These results indicate that Rabphilin-3A is localized on the synaptic vesicle in the presynapse.

Rab3A/Smg 25A, a small GTP-binding protein, is highly concentrated in presynapse of neurons and implicated in neurotransmitter release. We have recently identified a putative target protein for Rab3A, isolated its cDNA, and designated it as Rabphilin-3A. To examine whether Rabphilin-3A as well as Rab3A is localized at the sites of Ca(2+)-dependent exocytosis, we investigated here localization of Rabphilin-3A and Rab3A in comparison with the sites of exocytosis in the differentiated PC12 cells. Rabphilin-3A as well as Rab3A was highly concentrated at the tips of the neurites where Ca(2+)-dependent exocytosis took place. Inversely, neither Rabphilin-3A nor Rab3A was concentrated at the tips of the neurites where Ca(2+)-dependent exocytosis did not take place. These results suggest that Rabphilin-3A as well as Rab3A constitutes a part of the machinery necessary for neurotransmitter release.

Ultrastructural localization of protein kinase C (PKC) beta-subspecies in neuromuscular junctions of the rat lumbrical muscle was investigated by the immunoperoxidase and immunofluorescence methods. By light microscopy, PKC beta-like immunoreactivity (PKC beta-LIR) was found in the axon terminal expansions as well as in the preterminal axons. By confocal laser scanning microscopy, the staining for PKC beta-like immunoreactivity was more intense in the presynaptic regions just in contact with the acetylcholine receptor stained by FITC-alpha-bungarotoxin. By electron microscopy, PKC beta-like immunoreactivity was distributed non-uniformly in the terminal expansions. In the terminal expansions, PKC beta-like immunoreactivity was accumulated in the presynaptic regions in contact with the post-synaptic folds. This accumulation was approximately 0.1-0.2 microns in diameter, which comprised a part of the presynaptic plasma membrane and a group of synaptic vesicles adjacent to it. Weak immunoreactivity was also found diffusely in the axoplasmic matrix. The discrete presynaptic accumulation of PKC beta-subspecies may represent the strategical localization specialized for the effective regulation of neurotransmitter release.

smg p25A is a small G protein which has been suggested to regulate neurotransmitter release from the synapses. We investigated here the ultrastructural localization of this small G protein in the rat neuromuscular junction by an immunoperoxidase method. The results showed that smg p25A was distributed non-uniformly on the presynaptic plasma membrane and among the synaptic vesicles with the focal accumulation on the discrete presynaptic sites which corresponded to the active zones, the regions of the presynaptic plasma membrane specialized for the exocytosis of the synaptic vesicles. This unique distribution of smg p25A suggests that it plays an important role in the attachment and fusion of the synaptic vesicles with the active zones.

Cytological changes in mouse decidual cells during the early stages from 4.5th to 11th day of pregnancy were examined by electron microscopy with special reference to gap junctions. The most noticeable feature of decidual cells was that there was an abundance of various-shaped gap junctions such as flat, undulated, omega-shaped, and annular-shaped gap junctions. Serial sectioning revealed that annular-shaped gap junctions were separated from the decidual cell plasma membrane. Intramembranous particles (IMPs) of the gap junctions as seen by freeze-fracture displayed a well-packed arrangement and a homogeneous size. Degenerative changes first appeared in decidual cells directly contiguous with trophoblasts on the 7th day, and spread to the deeper area as clearly seen on the 8th day. Along with degeneration of decidual cells, annular-shaped gap junctions were enfolded and gradually degraded by lysosomes. IMPs of such degenerative gap junctions were irregularly arranged and heterogenous in size. The decidual tissue became thin with elongated decidual cells as the placental disc grew on the 10th day. Extremely long undulated gap junctions were present in decidual cells, and a small number of annular-shaped gap junctions were also found in the cytoplasm. The presence of abundant gap junctions as demonstrated in the present study suggests that decidual cells will be able to develop as well as to function synchronously. In addition, it is suggested that redundant gap junctions become annular-shaped to be finally degraded by lysosomes.

The present report reviews the physiological and morphological specializations of Pacinian corpuscles and other mechanoreceptors that are present in the skin and connective tissues of the body as well as the cochlea. The remarkable sensitivity of Pacinian corpuscles is such that the only form of mechanical energy that could be perceived by a Pacinian corpuscle is a sound wave. In fact the human finger as demonstrated by Munger and Ide (1987) can perceive sound waves when water is the coupling agent. The structural specializations are equally remarkable with extensive membrane specializations of both the inner core and inner portion of the outer core. The halves of the inner core are each coupled with gap junctions and the inner portion of the outer core joined with numerous tight junctions. The cleft regions have specializations involving the axolemma that consist of numerous axonal spines containing bundles of filaments projecting into the cleft of the inner core. These structural specializations are thought to represent specializations for mechano-electric transduction analogous in many respects to the hair cells of the cochlea. A hypothesis for mechano-electric transduction is presented that may account in part for the extreme sensitivity of Pacinian corpuscles and other mechanoreceptors.