Abstract
Background
High estradiol (E
2
) levels are linked to an increased risk of venous thromboembolism; however, the underlying molecular mechanism(s) remain poorly understood. We previously ...identified an E
2
-responsive microRNA (miR), miR-494–3p, that downregulates protein S expression, and posited additional coagulation factors, such as tissue factor, may be regulated in a similar manner via miRs.
Objectives
To evaluate the coagulation capacity of cohorts with high physiological E
2
, and to further characterize novel E
2
-responsive miR and miR regulation on tissue factor in E
2
-related hypercoagulability.
Methods
Ceveron Alpha thrombin generation assay (TGA) was used to assess plasma coagulation profile of three cohorts. The effect of physiological levels of E
2
, 10 nM, on miR expression in HuH-7 cells was compared using NanoString nCounter and validated with independent assays. The effect of tissue factor-interacting miR was confirmed by dual-luciferase reporter assays, immunoblotting, flow cytometry, biochemistry assays, and TGA.
Results
Plasma samples from pregnant women and women on the contraceptive pill were confirmed to be hypercoagulable (compared with sex-matched controls). At equivalent and high physiological levels of E
2
, miR-365a-3p displayed concordant E
2
downregulation in two independent miR quantification platforms, and tissue factor protein was upregulated by E
2
treatment. Direct interaction between miR-365a-3p and
F3-
3′UTR was confirmed and overexpression of miR-365a-3p led to a decrease of (1) tissue factor mRNA transcripts, (2) protein levels, (3) activity, and (4) tissue factor-initiated thrombin generation.
Conclusion
miR-365a-3p is a novel tissue factor regulator. High E
2
concentrations induce a hypercoagulable state via a miR network specific for coagulation factors.
Sarcopenic obesity (SO) is associated with poorer physical outcomes and functional status in the older adult. A proinflammatory milieu associated with central obesity is postulated to enhance muscle ...catabolism. We set out to examine associations of the chemokine monocyte chemoattractant protein-1 (MCP-1) in groups of older adults, with sarcopenia, obesity, and the SO phenotypes.
A total of 143 community dwelling, well, older adults were recruited. Cross-sectional clinical data, physical performance, and muscle mass measurements were collected. Obesity and sarcopenia were defined using revised National Cholesterol Education Program (NCEP) obesity guidelines and those of the Asian Working Group for Sarcopenia. Serum levels of MCP-1 were measured by enzyme-linked immunosorbent assay (ELISA).
In all, 25.2% of subjects were normal, 15.4% sarcopenic, 48.3% obese, and 11.2% were SO. The SO groups had the lowest appendicular lean mass, highest percentage body fat, and lowest performance scores on the Short Physical Performance Battery and grip strength. The MCP-1 levels were significantly different, with the highest levels found in SO participants (P<0.05).
Significantly raised MCP-1 levels in obese and SO subjects support the theory of chronic inflammation due to excess adiposity. Longitudinal studies will reveal whether SO represents a continuum of obesity causing accelerated sarcopenia and cardiovascular events, or the coexistence of two separate conditions with synergistic effects affecting functional performance.
Mission: “the role the medical student sees for him- or her-self in relation to others” Goldie’s social psychological levels of analysis 16 Goldie’s social psychological levels of analysis builds on ...the Personality and Social Structure Perspective (PSSP) model, involving the application of identity formation and identity maintenance process. Social identity: “at this level, the student is most influenced by the pressure to fit into the available identity ‘moulds’ created by cultural and role-related pressures” Jarvis-Sellinger’s conceptual framework of professional identity formation 65 A model of action, based on grounded theory, that illustrates how the interactions between context, focus and catalyst aid medical students in processing their emerging professional identities. Within this framework, context refers to the “details medical students use to describe an encounter or activity that has provoked reflection”; focus refers to what the medical students pay attention to in the encounter or activity; catalyst refers to a stimulus such as a learning event that triggers conscious thinking about professional identity within a specific context; while the process “signifies the ways in which medical students experience and describe navigating or negotiating their own emerging professional identities”. Socialization is influenced by multiple factors including the healthcare system; learning environment; role models and mentors; clinical and non-clinical experiences; self-assessment; formal teaching and assessment; symbols and rituals; family and friends; attitudes of patients, peers, health care professionals and the public; and isolation from peers.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•Inter-muscular adipose tissue mass (IMAT) is highest in sarcopenic obese and obese groups.•IMAT is significantly inversely correlated with muscle strength and gait speed in obese subgroup.•IMAT ...independently predicted poorer grip strength and Short Physical Performance Battery scores.•Sarcopenic Obesity is independently associated with muscle strength.•A significant correlation of IMAT with Monocyte Chemoattractant Protein-1, a novel biomarker of adipose tissue inflammation, is also observed.
The presence of concomitant sarcopenia and obesity in sarcopenic obesity (SO) confers worse functional, morbidity and mortality outcomes compared to either alone. Excess adiposity and central redistribution of fats are associated with systemic inflammation and ectopic tissue fat infiltration in forms of Intermuscular adipose tissue (IMAT). Our study examines the profile of IMAT across a spectrum of body compositions and associations with physical performance and inflammatory biomarkers including Monocyte Chemoattractant Protein-1 (MCP-1), a novel biomarker of adipose tissue inflammation.
187 community dwelling elderly participants were recruited and classified into 4 subgroups: normal, obese, sarcopenia and SO, using validated criteria for sarcopenia and waist circumference to define central obesity. We performed magnetic resonance imaging of mid-thigh sections to segment IMAT and muscle. Participants were assessed for muscle strength, physical performance and blood inflammatory biomarkers of interleukin-6, C-Reactive Protein and MCP-1. We examined correlation of IMAT(ratio) with muscle function measures and blood biomarkers. Multiple regression analyses were used to examine the association of body composition types and IMAT(ratio) with muscle function.
IMAT(ratio) was highest in SO and obese groups. Overall, higher IMAT(ratio) is significantly associated with raised MCP-1, lower gait speed and muscle strength. SO had lowest scores in Short Physical Performance Battery (SPPB), gait speed, hand-grip and knee extension strength. IMAT(ratio) is independently associated with SPPB and handgrip strength, whilst SO is independently associated with muscle strength.
Our results suggest the possible role of IMAT as a candidate imaging biomarker for adipose tissue inflammation and associated poorer functional outcomes in SO.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The 8q24 region harbors multiple risk variants for distinct cancers, including >8 for prostate cancer. In this study, we conducted fine mapping of the 8q24 risk region (127.8-128.8Mb) in search of ...novel associations with common and rare variation in 4853 prostate cancer case patients and 4678 control subjects of African ancestry. All statistical tests were two-sided. We identified three independent associations at P values of less than 5.00×10(-8), all of which were replicated in studies from Ghana and Uganda (combined sample = 5869 case patients, 5615 control subjects; rs114798100: risk allele frequency RAF = 0.04, per-allele odds ratio OR = 2.31, 95% confidence interval CI = 2.04 to 2.61, P = 2.38×10(-40); rs72725879: RAF = 0.33, OR = 1.37, 95% CI = 1.30 to 1.45, P = 3.04×10(-27); and rs111906932: RAF = 0.03, OR = 1.79, 95% CI = 1.53 to 2.08, P = 1.39×10(-13)). Risk variants rs114798100 and rs111906923 are only found in men of African ancestry, with rs111906923 representing a novel association signal. The three variants are located within or near a number of prostate cancer-associated long noncoding RNAs (lncRNAs), including PRNCR1, PCAT1, and PCAT2. These findings highlight ancestry-specific risk variation and implicate prostate-specific lncRNAs at the 8q24 prostate cancer susceptibility region.
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Background: Accessible Cancer Care to Enable Support for Cancer Survivors (ACCESS) is a multidisciplinary survivorship care model launched at the National Cancer Centre Singapore, ...the largest ambulatory cancer centre serving 70% of adult cancer patients in the public sector. ACCESS employs routine distress screening to triage patients with varying care needs and complexities. This study aims to examine the feasibility, delivery, and acceptance of ACCESS in providing appropriate service referrals to cancer patients in clinical settings. Methods: As part of an ongoing evaluation, we evaluated ACCESS for a 6-month implementation period between September 2019 and February 2020. Feasibility was assessed by proportions of (1) eligible breast and gynecological cancer patients who completed the locally adapted Distress Thermometer (DT) screening tool, (2) highly distressed patients, and (3) highly distressed patients requiring multidisciplinary meetings (MDM). Delivery was characterized by the mode and number of supportive care team (SCT) reviews required. Acceptance rates of SCT reviews by distressed patients and the uptake rate of service referrals recommended by the SCT were tabulated. Results: ACCESS screened 1074/1471 (73.0%) of all eligible patients within the 6-month period and identified 239/1074 (22.3%) as highly distressed for follow-up with the SCT. Eventually, 84.5% agreed to SCT review, with approximately one-fourth (26.7%) requiring MDM reviews. The majority (62.4%) of all distressed patients were identified at their first DT completion, whereas 19.8% and 7.4% were identified at their second and third completions respectively. The most common modes of follow-up were phone reviews (49.9%) and face-to-face in clinic waiting areas (48.6%). The SCT recommended 80 referrals to distressed patients for the following services: psychosocial (27.2%), cancer rehabilitation (5.9%), and home hospice (5.0%). The acceptance rates of the referrals for psychosocial, rehabilitation, and hospice services were 43.6%, 75.0%, and 80.0% respectively. Conclusions: ACCESS is a feasible model for triaging Asian cancer patients based on distress levels, and identifying complex patients requiring care personalization through MDM. The poorer acceptance rate of psychosocial services highlights patients’ preference for interventions targeting physical than psychosocial issues. Future studies should explore whether the uptake of psychosocial services is higher in the post-COVID era.
Abstract only Background and Aims: Endovascular Thrombectomy (EVT) for anterior circulation large vessel occlusion(LVO) in late time windows (over 6 hours) has been validated. Studies utilised ...advanced neuroimaging to select patients with small ischaemic cores. We have evaluated if routine imaging with non-contrast CT (NCCT) is inferior to CT Perfusion (CTP) to select patients for EVT in late time windows. Method: A prospectively maintained database of all EVT patients at two tertiary referral centres was retrospectively interrogated to identify anterior circulation LVO patients, with groin puncture times over 6 hours from symptom onset or time last seen well. Subjects were divided into those that underwent CTP in addition to routine NCCT and CT angiography (CTA) and those that were selected by NCCT/CTA alone. Results: A total of 85 patients were included, 39 (46%) had CTP (CTP+). No significant difference between baseline characteristics of CTP+ vs CTP- groups such as age (mean 66 vs 74, p=0.26), gender (male 49% vs 59%, p=0.36), median ASPECT (8 vs 8, p=0.84) and median NIHSS (13 vs 13, p=0.42) were observed. The two groups were also well matched with respect to time metrics including onset to imaging time (mean 519 vs 477 mins, p=0.41), time to groin puncture (mean 733 vs 690 mins, p=0.90) and procedure time (mean 41 vs 38 mins, p=0.94). No significant difference between early neurological recovery (36% vs 44%, p=0.48), 90 day mean utility weighted mRS (6.2, 95% CI 5.1, 7.4 vs 6.4, 95% CI 5.2, 7.5 p=0.75), rates of functional independence at 90 days (60% vs 64%, p=0.76), and rates of symptomatic haemorrhage (8 vs 9%, p=0.41) was observed between the groups. Conclusion: In late time windows, anterior circulation LVO patients selected for EVT based on routine imaging had non-inferior outcomes to those who underwent CTP. Our data suggests that late time window patients who do not have access to advanced neuroimaging should not be excluded from EVT.
Resistance mechanisms are typically uncovered by identifying sequence variation in known candidate genes, however this strategy can be problematic for species with no reference data in known ...relatives. Here we take a genomic approach to identify resistance to pyrethroids in the redlegged earth mite, Halotydeus destructor, a member of the Penthalidae family of mites that are virtually uncharacterized genetically. Based on shallow genome sequencing followed by a genome assembly, we first identified contigs of the H. destructor parasodium channel gene. By linking variation in this gene to known resistant phenotypes, we located a single nucleotide polymorphism in resistant mites. This polymorphism results in a leucine (L) to phenylalanine (F) amino acid substitution in the II6 region (predicted) of the gene (L1024F). This novel mutation has not previously been linked to pyrethroid resistance, although other polymorphisms have been identified in the two-spotted spider mite, Tetranychus urticae at the same locus (L1024V). The sequencing approach was successful in generating a candidate polymorphism that was then validated using laboratory bioassays and field surveys. A high throughput Illumina-based sequencing diagnostic was developed to rapidly assess resistance allele frequencies in pools of mites sourced from hundreds of populations across Australia. Resistance was confirmed to be widespread in the southern wheatbelt region of Western Australia. Two different resistance mutations were identified in field populations, both resulting in the same amino acid substitution. The frequency and distribution of resistance amplicon haplotypes suggests at least two, and probably more independent origins of resistance.
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•We compared contigs of the parasodium channel gene from resistant and susceptible mites.•A leucine to phenylalanine mutation (L1024F) was linked to pyrethroid resistance.•A high throughput sequencing diagnostic was applied to populations across Australia.•Field resistance was highly correlated to the frequency of the candidate mutation.•Resistance was confined to, but widespread in southern Western Australia.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Interventions to prevent osteoporosis by increasing dairy intake or physical activity in young women have been limited to increasing osteoporosis knowledge and awareness. However, findings have shown ...that this does not always lead to a change in behaviors. Self-monitoring using mobile devices in behavioral interventions has yielded significant and positive outcomes. Yet, to our knowledge, mobile self-monitoring has not been used as an intervention strategy to increase calcium intake, particularly in young women, for better bone health outcomes.
As development and testing of mobile app-based interventions requires a sequence of steps, our study focused on testing the acceptability and usability of Calci-app, a dietary app to self-monitor calcium consumption, before it is used in a behavioral change intervention in young women aged 18-25 years.
Calci-app development followed 4 steps: (1) conceptualization, (2) development and pretesting, (3) pilot testing, and (4) mixed methods evaluation.
We present the development process of Calci-app and evaluation of the acceptability and usability of the app in young women. Overall, 78% (31/40) of study participants completed the 5-day food record with high compliance levels (defined as more than 3 days of full or partial completion). There was a significant reduction in the proportion of participants completing all meal entries over the 5 days (P=.01). Participants generally found Calci-app easy and convenient to use, but it was time-consuming and they expressed a lack of motivation to use the app.
We present a detailed description of the development process of Calci-app and an evaluation of its usability and acceptability to self-monitor dietary calcium intake. The findings from this preliminary study demonstrated acceptable use of Calci-app to self-monitor calcium consumption. However, for regular and long-term use the self-monitoring function in Calci-app could be expanded to allow participants to view their total daily calcium intake compared with the recommended daily intake. Additionally, to facilitate sustainable lifestyle behavior modifications, a combination of various behavior change techniques should be considered, such as education, goal setting, and advice to participants based on their stage of change. The feedback on barriers and facilitators from testing Calci-app will be used to design a bone health mHealth intervention to modify risky lifestyle behaviors in young women for better bone health outcomes.
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