Long-lasting memory of jasmonic acid-dependent immunity requires DNA demethylation and ARGONAUTE1.

Stress can have long-lasting impacts on plants. Here we report the long-term effects of the stress hormone jasmonic acid (JA) on the defence phenotype, transcriptome and DNA methylome of Arabidopsis. Three weeks after transient JA signalling, 5-week-old plants retained induced resistance (IR) against herbivory but showed increased susceptibility to pathogens. Transcriptome analysis revealed long-term priming and/or upregulation of JA-dependent defence genes but repression of ethylene- and salicylic acid-dependent genes. Long-term JA-IR was associated with shifts in glucosinolate composition and required MYC2/3/4 transcription factors, RNA-directed DNA methylation, the DNA demethylase ROS1 and the small RNA (sRNA)-binding protein AGO1. Although methylome analysis did not reveal consistent changes in DNA methylation near MYC2/3/4-controlled genes, JA-treated plants were specifically enriched with hypomethylated ATREP2 transposable elements (TEs). Epigenomic characterization of mutants and transgenic lines revealed that ATREP2 TEs are regulated by RdDM and ROS1 and produce 21 nt sRNAs that bind to nuclear AGO1. Since ATREP2 TEs are enriched with sequences from IR-related defence genes, our results suggest that AGO1-associated sRNAs from hypomethylated ATREP2 TEs trans-regulate long-lasting memory of JA-dependent immunity.

Polarisation-sensitive optical coherence tomography measurement of retardance in fibrosis, a non-invasive biomarker in patients with systemic sclerosis.

Polarisation-sensitive optical coherence tomography (PS-OCT) offers a novel, non-invasive method of assessing skin fibrosis in the multisystem disease systemic sclerosis (SSc) by measuring collagen retardance. This study aimed to assess retardance as a biomarker in SSc. Thirty-one patients with SSc and 27 healthy controls (HC) underwent PS-OCT imaging. 'Skin score' was assessed by clinical palpation (0-3 scale). A subset of ten patients and ten age/sex-matched HC had a biopsy and longitudinal imaging. Histological assessment included quantification of epidermal thickness, collagen content (to assess fibrosis) and matrix metalloproteinase (MMP) activity (in situ zymography). PS-OCT images were assessed for epidermal thickness (structure) and fibrosis (retardance). Positive correlation was observed between epidermal thickness as measured by histology and structural PS-OCT (r = 0.79; p < 0.001). Retardance was: HC mean 0.21 (SD 0.21) radian/pixel; SSc skin score 0, 0.30 (0.19); skin score 1, 0.11 (0.16); skin score 2, 0.06 (0.12); skin score 3, 0.36 (0.35). Longitudinal retardance decreased at one-week across groups, increasing at one-month for HC/skin score 0-1; HC biopsy site retardance suggests scarring is akin to fibrosis. Relationships identified between retardance with both biopsy and skin score data indicate that retardance warrants further investigation as a suitable biomarker for SSc-related fibrosis.

The European baseline series: Criteria for allergen inclusion (with reference to formaldehyde releasers).

Existing criteria for inclusion in the European baseline series are summarized. Additional criteria are developed to aid decision making where the current criteria do not yield an unequivocal result. These include a consideration of whether an allergen (hapten) is better placed in a special series and the frequency with which an allergen cross-reacts with existing markers in the baseline series.

The evolution of pulmonary function in childhood onset Mucopolysaccharidosis type I.

Respiratory outcomes in Mucopolysaccharidosis Type I (MPS I), have mainly focused on upper airway obstruction, with the evolution of the restrictive lung disease being poorly documented. We report the long-term pulmonary function outcomes and examine the potential factors affecting these in 2 cohorts of MPS I patients, those who have undergone Haematopoietic Stem Cell Transplantation (HSCT) and those treated with Enzyme Replacement Therapy (ERT). The results were stratified using the American Thoracic Society (ATS) guidelines. 66 patients, capable of adequately performing testing, were identified by a retrospective case note review, 46 transplanted (45 Hurler, 1 Non-Hurler) and 20 having ERT (17 Non-Hurler and 3 Hurler diagnosed too late for HSCT). 5 patients died; 4 in the ERT group including the 3 Hurler patients. Overall 14% of patients required respiratory support (non-invasive ventilation (NIV) or supplemental oxygen)) at the end of follow up. Median length of follow-up was 12.2 (range = 4.9-32) years post HSCT and 14.34 (range = 3.89-20.4) years on ERT. All patients had restrictive lung disease. Cobb angle and male sex were significantly associated with more severe outcomes in the HSCT cohort, with 49% having severe to very severe disease. In the 17 Non-Hurler ERT treated patients there was no variable predictive of severity of disease with 59% having severe to very severe disease. During the course of follow up 67% of the HSCT cohort had no change or improved pulmonary function as did 52% of the ERT patients. However, direct comparison between therapeutic modalities was not possible. This initial evidence would suggest that a degree of restrictive lung disease is present in all treated paediatrically diagnosed MPS I and is still a significant cause of morbidity, though further stratification incorporating diffusing capacity for carbon monoxide (DLCO) is needed.

Coronavirus disease 2019 communication: novel sign language system to aid surgical tracheostomy whilst wearing a respirator.

BACKGROUND: The coronavirus disease 2019 pandemic has necessitated rapid adaptations to all levels of clinical practice. Recently produced guidelines have suggested additional considerations for tracheostomy and advocated full personal protective equipment, including filtering facepiece code 3 masks. Air seal with filtering facepiece code 3 masks is often challenging, and full-face respirators and powered air-purifying respirators with hoods need to be employed. The infection prevention benefits of this equipment are accompanied by potential issues in communication. OBJECTIVE: In an attempt to minimise surgical error through miscommunication, the authors sought to introduce a simple sign language system that could be used as an adjunct during surgery. RESULTS: Following evaluation of pre-existing sign language platforms and consideration of multiple surgical factors, 14 bespoke hand signals were ultimately proposed. CONCLUSION: Whilst this novel sign language system aims to bridge the communicative gap created by additional personal protective equipment, further development and validation of the proposed tool might be beneficial.

Characterizing osmolyte chemical class hierarchies and functional group requirements for thermal stabilization of proteins.

Osmolytes are naturally occurring organic compounds that protect cellular proteins and other macromolecules against various forms of stress including temperature extremes. While biological studies have correlated the accumulation of certain classes of osmolytes with specific forms of stress, including thermal stress, it remains unclear whether or not these observations reflect an intrinsic chemical class hierarchy amongst the osmolytes with respect to effects on protein stability. In addition, very little is known in regards to the molecular elements of the osmolytes themselves that are essential for their functions. In this study, we use differential scanning fluorimetry to quantify the thermal stabilizing effects of members from each of the three main classes of protecting osmolytes on two model protein systems, C-reactive protein and tumor necrosis factor alpha. Our data reveals the absence of a strict chemical class hierarchy amongst the osmolytes with respect to protein thermal stabilization, and indicates differential responses of these proteins to certain osmolytes. In the second part of this investigation we dissected the molecular elements of amino acid osmolytes required for thermal stabilization of myoglobin and C-reactive protein. We show that the complete amino acid zwitterion is required for thermal stabilization of myoglobin, whereas removal of the osmolyte amino group does not diminish stabilizing effects on C-reactive protein. These disparate responses of proteins to osmolytes and other small molecules are consistent with previous observations that osmolyte effects on protein stability are protein-specific. Moreover, the data reported in this study support the view that osmolyte effects cannot be fully explained by considering only the solvent accessibility of the polypeptide backbone in the native and denatured states, and corroborate the need for more complex models that take into account the entire protein fabric.

Radiological characterisation of graphite components in Advanced Gas-cooled Reactor cores.

As the Advanced Gas-cooled Reactors approach the end of generation, research and characterisation are required to support the decommissioning strategy. Radiological data for AGR graphite are negligible and the radiological inventory of the AGR core and other graphite components rely on activation modelling. This is the first study of C-14 activity and its release behaviour in AGR core graphite and its associated carbonaceous deposits and provides valuable information that can support decommissioning activities. In combination with corresponding studies on Magnox core graphite, significant understanding is attained on the main C-14 precursors in the graphite and the deposits. In addition, this study reports C-14, H-3 and gamma spectrometry data on AGR graphite fuel sleeves. This is a waste stream that is currently stored in heavily engineered stores at a significant cost. The data indicate that alternative storage and disposal options with a lower environmental and financial impact are worth considering.

A qualitative study of the role of Australian general practitioners in the surgical management of obesity.

General practitioners (GPs) are increasingly managing patients with class 2 and 3 obesity (body mass index [BMI] > 35 and 40 kg/m2 , respectively). Bariatric surgery is considered for patients with class 2 obesity and comorbidities or class 3 obesity where sustained weight loss using non-surgical interventions has not been achieved. In Australia, GPs facilitate access to surgery through referral processes, but the nature of GP involvement in bariatric pre- and post-surgery care is currently unclear. This qualitative study involved 10 in-depth interviews with GPs and 20 interviews with adults who had all undergone laparoscopic adjustable gastric banding (LAGB) for weight management in Tasmania, Australia. Interviews were transcribed and analysed thematically. Referrals for bariatric surgery commonly occurred at the patient's request or to manage comorbidity. Consistent with previous studies, for GPs, referral patterns were influenced by previous case experience and patients' financial considerations. Accessibility of surgery was also a consideration. Post-surgery, there was a lack of clarity about the role of GPs, with patients generally preferring the surgical team to manage the LAGB. In bariatric surgery, patient preference for surgery, access and comorbidity are key drivers for referral and post-surgical monitoring and support. Greater role clarity and enhanced collaboration between surgeons, GPs and patients following surgery is likely to enhance the experience and outcomes for patients.

Effectiveness of extensive sinus surgery with post-operative medical management for chronic rhinosinusitis.

OBJECTIVE: To prospectively assess treatment outcomes of chronic rhinosinusitis patients undergoing functional endoscopic sinus surgery and post-operative medical treatment over a prolonged follow-up period. METHODS: Patients undergoing functional endoscopic sinus surgery in the tertiary referral practice of a single surgeon were studied prospectively. Symptoms were scored by patients pre-operatively and over a minimum follow-up period of 12 months. RESULTS: The study comprised 200 non-consecutive patients. The median pre-operative symptom score was 16 (out of a maximum of 25) (95 per cent confidence interval = 15 to 17). Symptom scores reduced to a median of 7 (95 per cent confidence interval = 6 to 8) after 12 months of follow up (p < 0.0001). The median symptom score improved for all symptoms and across all patient subgroups. CONCLUSION: Extensive functional endoscopic sinus surgery offers significant and durable symptom improvement in patients with chronic rhinosinusitis refractory to medical treatment. This improvement extends to all patient subgroups. Prolonged medical therapy is recommended after functional endoscopic sinus surgery.

The support needs of patients waiting for publicly funded bariatric surgery - implications for health service planners.

The objective of this study was to investigate the experience of waiting for publicly funded bariatric surgery in an Australian tertiary healthcare setting. Focus groups and individual interviews involving people waiting for or who had undergone publicly funded bariatric surgery were audio-recorded, transcribed and analysed thematically. A total of 11 women and 6 men engaged in one of six focus groups in 2014, and an additional 10 women and 9 men were interviewed in 2015. Mean age was 53 years (range 23-66); mean waiting time was 6 years (range 0-12), and mean time since surgery was 4 years (range 0-11). Waiting was commonly reported as emotionally challenging (e.g. frustrating, depressing, stressful) and often associated with weight gain (despite weight-loss attempts) and deteriorating physical health (e.g. development of new or worsening obesity-related comorbidity or decline in mobility) or psychological health (e.g. development of or worsening depression). Peer support, health and mental health counselling, integrated care and better communication about waitlist position and management (e.g. patient prioritization) were identified support needs. Even if wait times cannot be reduced, better peer and health professional supports, together with better communication from health departments, may improve the experience or outcomes of waiting and confer quality-of-life gains irrespective of weight loss.

Relationships between range access as monitored by radio frequency identification technology, fearfulness, and plumage damage in free-range laying hens.

Severe feather-pecking (SFP), a particularly injurious behaviour in laying hens (Gallus gallus domesticus), is thought to be negatively correlated with range use in free-range systems. In turn, range use is thought to be inversely associated with fearfulness, where fearful birds may be less likely to venture outside. However, very few experiments have investigated the proposed association between range use and fearfulness. This experiment investigated associations between range use (time spent outside), fearfulness, plumage damage, and BW. Two pens of 50 ISA Brown laying hens (n=100) were fitted with radio frequency identification (RFID) transponders (contained within silicone leg rings) at 26 weeks of age. Data were then collected over 13 days. A total of 95% of birds accessed the outdoor run more than once per day. Birds spent an average duration of 6.1 h outside each day over 11 visits per bird per day (51.5 min per visit). The top 15 and bottom 15 range users (n=30), as determined by the total time spent on the range over 13 days, were selected for study. These birds were tonic immobility (TI) tested at the end of the trial and were feather-scored and weighed after TI testing. Birds with longer TI durations spent less time outside (P=0.01). Plumage damage was not associated with range use (P=0.68). The small group sizes used in this experiment may have been conducive to the high numbers of birds utilising the outdoor range area. The RFID technology collected a large amount of data on range access in the tagged birds, and provides a potential means for quantitatively assessing range access in laying hens. The present findings indicate a negative association between fearfulness and range use. However, the proposed negative association between plumage damage and range use was not supported. The relationships between range use, fearfulness, and SFP warrant further research.

UK rates of occupational skin disease attributed to rubber accelerators, 1996-2012.

BACKGROUND: Natural and synthetic rubbers containing rubber accelerators are well-known causes of allergic contact dermatitis (ACD). Latex contact urticaria (CU) has been widely reported, especially when powdered latex glove use was commonplace. Consequently, interventions to reduce latex exposure by altering glove manufacture were introduced. OBJECTIVE: This study aimed to analyse trends in UK-reported incidence of occupational skin disease associated with rubber accelerators. METHOD: We analysed cases reported to EPIDERM (part of The Health and Occupation Research network) of occupational ACD caused by natural and synthetic rubber products, between 1996 and 2012. RESULTS: For the studied period, a decreasing incidence of ACD associated with rubber products was found, with an average annual change of -1.2% [95% confidence interval (CI) -3.1 to 0.7]. The number of cases of latex CU (n = 580) significantly declined. The number of cases of ACD caused by mercapto mix and mercaptobenzothiazole (n = 177) and thiuram mix (n = 603) also declined. Reports of ACD associated with carba mix and its constituents (n = 219) increased significantly, by an average annual percentage of 10.1% (95%CI: 6.1-14.2). Twenty-six cases of ACD caused by rarer rubber compounds were identified, highlighting skin disease attributable to less widely recognized chemicals. CONCLUSIONS: These data show a falling reported incidence of occupational ACD attributed to rubber chemicals, but within this a significant rise attributable to the constituents of the carba mix. Clinicians should recognize the changing diversity of chemicals used in rubber manufacturing, and consider including carba mix in their baseline series and testing beyond this in suspect cases to avoid false-negative results.

Hand eczema and stratum corneum ceramides.

BACKGROUND: Hand eczema (HE) is a multifactorial disease, comprising different aetiological conditions and different morphologies. There are two aetiologically distinct groups of HE recognised: exogenous, such as contact dermatitis (allergic and/or irritant HE) and endogenous, such as the classic hyperkeratotic HE. Differences in the skin barrier properties of these two conditions could theoretically be expected. AIM: To examine whether differences exist in the lipid profile and the susceptibility of the stratum corneum (SC) in patients with allergic/irritant HE and those with hyperkeratotic HE. METHODS: Using cyanoacrylate, SC samples were taken from 23 patients with allergic/irritant HE and 15 with hyperkeratotic HE for lipid analysis by high-performance thin-layer chromatography (HPTLC). Samples were also taken from adjacent, unaffected skin. Severity of HE was assessed by the Hand Eczema Severity Index (HECSI), and skin barrier susceptibility was assessed by measuring transepidermal water loss (TEWL) after a 24-hour patch test with sodium lauryl sulfate (SLS). RESULTS: No statistically significant difference was found between groups for the lipid analysis or for skin susceptibility to SLS. We found a significantly higher HECSI score for hyperkeratotic HE compared with irritant or allergic HE (P = 0.02). CONCLUSIONS: There appears to be no difference in skin barrier between allergic/irritant HE (exogenous eczema) and hyperkeratotic HE (endogenous eczema) with regard to SC lipids or susceptibility to SLS.

Investigating work-related neoplasia associated with solar radiation.

BACKGROUND: Both solar and non-solar exposures associated with occupation and work tasks have been reported as skin carcinogens. In the UK, there are well-established surveillance schemes providing relevant information, including when exposures took place, occupation, location of work and dates of symptom onset and diagnosis. AIMS: To add to the evidence on work-related skin neoplasia, including causal agents, geographical exposure and time lag between exposure and diagnosis. METHODS: This study investigated incident case reports of occupational skin disease originating from clinical specialists in dermatology reporting to a UK-wide surveillance scheme (EPIDERM) by analysing case reports of skin neoplasia from 1996 to 2012 in terms of diagnosis, employment, suspected causal agent and symptom onset. RESULTS: The suspected causal agent was 'sun/sunlight/ultraviolet light' in 99% of the reported work-related skin neoplasia cases. Most cases reported (91%) were in males, and the majority (62%) were aged over 65 at the time of reporting. More detailed information on exposure was available for 42% of the cases, with the median time from exposure to symptom onset ranging from 44 (melanoma) to 57 (squamous cell carcinoma) years. Irrespective of diagnostic category, the median duration of exposure to 'sun/sunlight/ultraviolet light' appeared longer where exposures occurred in the UK (range 39-51 years) rather than outside the UK (range 2.5-6.5 years). CONCLUSIONS: It is important to provide effective information about skin protection to workers exposed to solar radiation, especially to outdoor workers based outside the UK.

Trial for Reducing Weight Retention in New Mums: a randomised controlled trial evaluating a low intensity, postpartum weight management programme.

BACKGROUND: Failure to return to pregnancy weight by 6 months postpartum is associated with long-term obesity, as well as adverse health outcomes. This research evaluated a postpartum weight management programme for women with a body mass index (BMI) > 25 kg m(-2) that combined behaviour change principles and a low-intensity delivery format with postpartum nutrition information. METHODS: Women were randomised at 24-28 weeks to control (supported care; SC) or intervention (enhanced care; EC) groups, stratified by BMI cohort. At 36 weeks of gestation, SC women received a 'nutrition for breastfeeding' resource and EC women received a nutrition assessment and goal-setting session about post-natal nutrition, plus a 6-month correspondence intervention requiring return of self-monitoring sheets. Weight change, anthropometry, diet, physical activity, breastfeeding, fasting glucose and insulin measures were assessed at 6 weeks and 6 months postpartum. RESULTS: Seventy-seven percent (40 EC and 41 SC) of the 105 women approached were recruited; 36 EC and 35 SC women received a programme and 66.7% and 48.6% completed the study, respectively. No significant differences were observed between any outcomes. Median [interquartile range (IQR)] weight change was EC: -1.1 (9.5) kg versus SC: -1.1 (7.5) kg (6 weeks to 6 months) and EC: +1.0 (8.7) kg versus SC: +2.3 (9) kg (prepregnancy to 6 months). Intervention women breastfed for half a month longer than control women (180 versus 164 days; P = 0.10). An average of 2.3 out of six activity sheets per participant was returned. CONCLUSIONS: Despite low intervention engagement, the high retention rate suggests this remains an area of interest to women. Future strategies must facilitate women's engagement, be individually tailored, and include features that support behaviour change to decrease women's risk of chronic health issues.

Systematic review of lifestyle interventions to limit postpartum weight retention: implications for future opportunities to prevent maternal overweight and obesity following childbirth.

Postpartum weight retention can predict future weight gain and long-term obesity. Moreover, failure to lose weight gained during pregnancy can lead to increased body mass index for subsequent pregnancies, increasing the risk of adverse maternal and foetal pregnancy outcomes. This systematic review evaluates the effectiveness of lifestyle interventions aimed at reducing postpartum weight retention. Seven electronic databases were searched for intervention studies and trials enrolling women with singleton pregnancies and published in English from January 1990 to October 2012. Studies were included when postpartum weight was a main outcome and when diet and/or exercise and/or weight monitoring were intervention components. No limitations were placed on age, body mass index or parity. Eleven studies were identified as eligible for inclusion in this review, of which 10 were randomized controlled trials. Seven studies were successful in decreasing postpartum weight retention, six of which included both dietary and physical activity components, incorporated via a range of methods and delivered by a variety of health practitioners. Few studies utilized modern technologies as alternatives to traditional face-to-face support and cost-effectiveness was not assessed in any of the studies. These results suggest that postpartum weight loss is achievable, which may form an important component of obesity prevention in mothers; however, the optimal setting, delivery, intervention length and recruitment approach remains unclear.

The ToT study: helping with Touch or Talk (ToT): a pilot randomised controlled trial to examine the clinical effectiveness of aromatherapy massage versus cognitive behaviour therapy for emotional distress in patients in cancer/palliative care.

UNLABELLED: Distress associated with cancer often presents with symptoms of depression and/or anxiety. Cognitive Behaviour Therapy (CBT) is one of the most effective psychological treatments. Complementary therapies, especially aromatherapy massage (AM), are also popular and alleviate anxiety. No studies have directly compared these two treatments. AIMS: The aim of this study is to (1) test the feasibility of recruitment into a randomised controlled trial of AM versus CBT in patients with cancer; (2) test and modify the intervention; (3) determine whether changes in outcomes were consistent with published data. METHODS: Patients at all stages of cancer, recruited from oncology outpatient clinics and screening eight or more for anxiety and/or depression on the HADS, were randomised to Treatment as Usual (TAU) plus up to eight sessions weekly of either AM or CBT, offered within 3 months. The POMS was collected at baseline and 3 and 6 months post baseline. RESULTS: Of those suitable, over 60% (39/63) participated (AM, n = 20; CBT, n = 19) and over 90% (36/39) were followed up. Both packages were well received. The preference was for AM, with more sessions were taken up; (Mean number sessions AM = 7.2 (SD 2.0) and CBT = 5.4 (SD 3.1); P<0.05). Significant improvements in POMS (Total Mood, depression and anxiety scores) occurred with both interventions. Between-group comparison showed a non-significant trend towards greater improvement in depression with CBT. CONCLUSIONS: Recruitment was feasible; the interventions acceptable and engagement with treatment was high. Improvements with both interventions were observed. The beneficial effects on depression with CBT appeared to be sustained.

Lung cancer mortality in a cohort of UK cotton workers: an extended follow-up.

BACKGROUND: A recent systematic review and meta-analysis suggested that occupational exposure to endotoxins protects against lung cancer. To explore this hypothesis further, the follow-up of mortality of a cohort of 3551 workers, who were employed in the British cotton industry during 1966-1971, was extended by 23 years. METHODS: Subjects had originally been recruited to a survey of respiratory disease, which collected information about occupation and smoking habits. Cumulative exposures to endotoxins were estimated from data on endotoxin levels by work areas in cotton mills. Risks of lung cancer were estimated using survival modelling. RESULTS: During follow-up, 2018 deaths were recorded before the age of 90 years, including 128 deaths from lung cancer. After adjustment for smoking, hazard ratios (95% confidence intervals) for cumulative endotoxin exposures of ≤30,000, >30,000 and ≤200,000, >200,000 and ≤400,000, >400,000 and ≤600,000 and >600,000 endotoxin units (EU) m(-3) years were 1, 0.8 (0.5-1.6), 0.7 (0.4-1.3), 0.6 (0.3-1.0) and 0.5 (0.3-0.9), respectively (P for trend=0.005). CONCLUSION: Our findings strengthen the evidence that occupational exposure to endotoxins protects against lung cancer, and suggest that the effect depends on cumulative dose and persists after exposure ceases.

Acquired port-wine stain occurring in association with a congenital lesion.

Acquired port-wine stains (PWSs) are rare but well recognized, and have often been reported in association with localized trauma. Various drugs have also been implicated as aetiological factors. We report the case of a 71-year-old man with an extensive congenital PWS affecting the left side of the face, upper chest and upper back. At the age of 69 years, he began to develop similar areas on his right hand and forearm, left hand and left knee. This corresponded temporally to being started on simvastatin and metformin, both of which may promote angiogenesis.