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Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Cardiac Risk in the Young. Background Sudden cardiac death (SCD) seemingly affects young, healthy individuals and is therefore recognised as an important public health concern for athletes and non-athletes. However, systematic population screening is not recommended in the United Kingdom (UK). Concerns include the low reported incidence of SCD in young individuals, the efficacy of the electrocardiogram (ECG) and the lack of robust evidence on cardiac screening. We sought to determine the diagnostic yield of a nationwide cardiac screening programme in young individuals. Importantly, we sought to report on the frequency of false-negative screen-test results, which is underrecognized in the literature, and the incidence of sudden cardiac arrest (SCA) and SCD amongst individuals who underwent screening. Methods From 2007 through 2018, 104,369 consecutive individuals, aged 14 to 35 years, underwent voluntary cardiac screening (62% were male, 91% were non-athletes). Initial evaluation consisted of a health questionnaire (HQ), ECG, and clinical consultation. Selective on-site echocardiography was available at the discretion of the consulting physician. Clinical outcomes were sourced from the Office for National Statistics-Hospital-Episode-Statistics database and an online HQ. Results During screening 280 (0.27%) individuals were found to have a cardiac condition associated with SCA/SCD and 115 received potentially life-saving treatments. A further 166 (0.16%) with congenital or valvular abnormalities were identified. During a mean follow-up of 6.2 ± 2.5 years, an additional 86 individuals, considered to have normal screening, were found to have a cardiac condition associated with SCA/SCD.After screening there were 86 deaths. Cardiac disorders accounted for 20 deaths (23%), all of which were sudden. In addition, 15 individuals survived a SCA. Primary electrical disorders accounted for 21 (60%) of the 35 cases of SCA/SCD, followed by cardiomyopathies (n=6), and congenital or acquired coronary artery disease (n=5). On the basis of a total of 626,550 person-years (PY), the combined incidence of SCA/SCD was 1:17,901 PY (5.6 per 100,000 PY). Males were at 3.5-fold higher risk than females (1:12,488 PY vs 1:44,067 PY, p < 0.01). For prevention of SCA/SCD the programme’s sensitivity was 19.4% with a specificity of 97.5%. For identifying conditions associated with SCD, the programme’s sensitivity was 76.5% with a specificity was 97.8%. Conclusion Diseases that are associated with SCD were identified in 0.27% of young individuals who underwent cardiac screening. A further 86 (0.08%) conditions were identified after screening. The incidence of SCA and SCD was 5.6 per 100,000 person-years, which is considerable higher than previous estimates in the general population. Most of these events were due to confirmed or presumed primary electrical disorders that had not been detected on screening.

Funding Acknowledgements Type of funding sources: None. Background Considering that myocarditis is implicated in 5-15% of all exercise related sudden cardiac deaths in athletes, following a novel viral pandemic, the identification and risk-stratification of affected athletes remains an important priority. Given its widespread availability, the inclusion of a 12-lead electrocardiogram (ECG) is common to all consensus-based protocols from North America and Europe. However, a single cross-sectional ECG is problematic because several physiological repolarisation changes are also common manifestations in individuals with myopericarditis. Purpose The aim of our study was to report on the prevalence and diagnostic significance of de-novo ECG patterns following COVID-19 infection in a well-defined cohort of elite soccer players in the English, Dutch and Brazilian leagues. Methods In this multicentre observational study, between March 2020–May 2022, we evaluated consecutive athletes with COVID-19 infection. ECGs were reported in accordance with the International recommendations for ECG interpretation in athletes. The following patterns were also considered abnormal if they were not detected on the pre-COVID-19 infection ECG: PR-segment depression, new J-point and ST segment elevation, low QRS voltages, QRS fragmentation, new ST-segment depression, new T-wave inversion, biphasic T-waves and a reduction in the T-wave amplitude by 50% or T-wave flattening. Athletes exhibiting de-novo ECG changes underwent cardiovascular magnetic resonance (CMR) scans. One club mandated CMR scans for all players (n=30) following COVID-19 infection, despite the absence of cardiac symptoms or de-novo ECG changes. Results 511 soccer players (median age 21-years, IQR:18-26-years) were included, of which 88% were male and 58% white. 17 (3%) athletes demonstrated de-novo ECG changes, which included, a reduction in T-wave amplitude in the inferior and lateral leads (n=5), inferior leads (n=4) and lateral leads (n=4); inferior T-wave inversion (n=7), and ST-segment depression (n=2). 15 (88%) athletes with de-novo ECG changes revealed CMR evidence of inflammatory cardiac sequalae. All athletes who underwent a mandatory CMR irrespective of illness severity or ECG findings, had normal findings. Athletes revealing de-novo ECG changes, had a higher prevalence of cardiac symptoms (71% v 12%; p Conclusions 3% of athletes demonstrated de-novo ECG changes post COVID-19 infection, of which 88% were diagnosed with inflammatory cardiac sequalae. Most affected athletes exhibited cardiac symptoms; however de-novo ECG changes contributed to a diagnosis of cardiac inflammation in 17% of athletes without cardiac symptoms.

Supplementary Table S1; Supplementary Figures S1-S2. Supplementary Table 1. A) IC50 value of P7170 in pan-PI3K. B) Kinase inhibition data (ProQinase) of P7170 at 250 nM and 1. 5 μM.C) Kinase inhibition profile (KINOMEscan; 320 kinases) of P7170. D) IC50 values of selected kinases on treatment with P7170. Supplementary Figure S1. The growth response curves on treatment of P7170 on various patient-derived cancer cell lines. Supplementary Figure S2. P7170 induces autophagy in A2780 (A) and HCT116 (B) cells.

Lipid droplets (LDs) are dynamic organelles that contain an oil core mainly composed of triglycerides (TAG) that is surrounded by a phospholipid monolayer and LD-associated proteins called perilipins (PLINs). During LD biogenesis, perilipin 3 (PLIN3) is recruited to nascent LDs as they emerge from the endoplasmic reticulum. Here, we analyzed how lipid composition affects PLIN3 recruitment to membrane bilayers and LDs, and the structural changes that occur upon membrane binding. We found the TAG precursors phosphatidic acid and diacylglycerol (DAG) recruit PLIN3 to membrane bilayers and define an expanded Perilipin-ADRP-Tip47 (PAT) domain that preferentially binds DAG enriched membranes. Membrane binding induces a disorder/order transition of alpha helices within the PAT domain and 11-mer repeats, with intramolecular distance measurements consistent with the expanded PAT domain adopting a folded but dynamic structure upon membrane binding. In cells, PLIN3 is recruited to DAG enriched ER membranes, and this requires both the PAT domain and 11-mer repeats. This provides molecular details of PLIN3 recruitment to nascent LDs and identifies a function of the PAT domain of PLIN3 in DAG binding.

Background Identification of athletes with cardiac inflammation following COVID-19 can prevent exercise fatalities. The efficacy of pre and post COVID-19 infection electrocardiograms (ECGs) for detecting athletes with myopericarditis has never been reported. We aimed to assess the prevalence and diagnostic significance of novel 12-lead ECG patterns following COVID-19 infection in elite soccer players. Methods We conducted a multicentre study over a 2-year period involving 5 centres and 34 clubs and compared pre COVID and post COVID ECG changes in 455 consecutive athletes. ECGs were reported in accordance with the International recommendations for ECG interpretation in athletes. The following patterns were considered abnormal if they were not detected on the pre COVID-19 infection ECG: (a) biphasic T-waves; (b) reduction in T-wave amplitude by 50% in contiguous leads; (c) ST-segment depression; (d) J-point and ST-segment elevation >0.2 mV in the precordial leads and >0.1 mV in the limb leads; (e) tall T-waves ≥1.0 mV (f) low QRS-amplitude in >3 limb leads and (g) complete right bundle branch block. Athletes exhibiting novel ECG changes underwent cardiovascular magnetic resonance (CMR) scans. One club mandated CMR scans for all 28 (6%) athletes, despite the absence of cardiac symptoms or ECG changes. Results Athletes were aged 22±5 years (89% male and 57% white). 65 (14%) athletes reported cardiac symptoms. The mean duration of illness was 3±4 days. The post COVID ECG was performed 14±16 days following a positive PCR. 440 (97%) athletes had an unchanged post COVID-19 ECG. Of these, 3 (0.6%) had cardiac symptoms and CMRs resulted in a diagnosis of pericarditis. 15 (3%) athletes demonstrated novel ECG changes following COVID-19 infection. Among athletes who demonstrated novel ECG changes, 10 (67%) reported cardiac symptoms. 13 (87%) athletes with novel ECG changes were diagnosed with inflammatory cardiac sequelae; pericarditis (n=6), healed myocarditis (n=3), definitive myocarditis (n=2), and possible/probable myocarditis (n=2). The overall prevalence of inflammatory cardiac sequelae based on novel ECG changes was 2.8%. None of the 28 (6%) athletes, who underwent a CMR, in the absence of cardiac symptoms or novel ECG changes revealed any abnormalities. Athletes revealing novel ECG changes, had a higher prevalence of cardiac symptoms (67% v 12% p Conclusions 3% of elite soccer players demonstrated novel ECG changes post COVID-19 infection, of which almost 90% were diagnosed with cardiac inflammation during subsequent investigation. Most athletes with novel ECG changes exhibited cardiac symptoms. Novel ECGs changes contributed to a diagnosis of cardiac inflammation in 20% of athletes without cardiac symptoms. Funding Acknowledgement Type of funding sources: None.

Background Sudden cardiac death (SCD) in young individuals and athletes is generally caused by hereditary cardiac conditions, including cardiomyopathies such as hypertrophic cardiomyopathy (HCM). Although historically HCM has been reported as the predominant cause of SCD in young athletes, it is unclear as to what degree exercise is a trigger for possible fatal arrhythmias. Aim We aimed to report on the circumstances of SCD in a cohort of young individuals aged ≥10 and Methods We reviewed 6860 consecutive cases of SCD referred to our specialist cardiac pathology centre 1994 and 2020. SCD was defined as death from a cardiovascular cause within 12 hours of apparent well-being. All cases underwent detailed autopsy evaluation of the heart, including histological analysis, by expert cardiac pathologists. A minimum of 10 blocks of tissue were taken for histological analysis. HCM was defined by the presence of increased heart weight or increased wall thickness and significant myocyte disarray at histological examination. Results Of the total cases of SCD, 264 (4%) were due to HCM. Our cohort of young decedents comprised of 66 individuals (average age 21±5 years, males 76%). For the majority (n=52, 79%) SCD was the first manifestation of HCM. The average heart weight was 507±152 grams and left ventricular (LV) fibrosis was found in 28 (42%) cases (Figure 1A). Death was more common between 16 and 20 years of age (n=24) (Figure 1B). Death occurred during exertion in 25 (38%) individuals and at rest or during daily activities in the remaining 41 (62%), including 5 individuals who died during sleep. Male sex was more represented among decedents who died during exertion (88% compared with 68% in the group that died at rest, p=0.07); LV fibrosis was more commonly observed in individuals who died during exertion (56% compared with 34% in the group who died at rest, p=0.08). Younger individuals between 10–15 years of age died mostly during exercise (80%), in other age groups death occurred mainly at rest (33% in age group 16–20 years, 30% in age group 21–25 years, 33% in age group 26–30 years) (Figure 1B). Conclusions We observed a high age-related variability in terms of circumstances of death. In the context of HCM, our findings suggest that individuals aged 10–15 years are the most vulnerable in terms of exercise-related-SCD. This exemplifies the importance of preventative cardiac screening in young individuals who might be harbouring quiescent cardiac conditions associated with young SCD. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Acknowledgements: We thank the charitable organisation, Cardiac Risk in the Young (CRY) who fund and support the CRY Cardiovascular Pathology Unit and CRY database.

Situation awareness (SA) training is a vital part of healthcare training, and opportunities to provide SA training to healthcare workers are limited in low- and middle-income countries. We aimed to analyze undergraduate medical and nursing students' perception of their understanding of SA through an interprofessional obstetric neonatal emergency simulation workshop (ONE-Sim) and subsequently evaluate their perceived changes in SA understanding using the Endsley model ( Hum Factors 1995;37(1):32-64).Feedback on SA before and after the workshop was collected through questionnaire-based surveys. Thematic analysis was performed, with themes emerging from an inductive analysis followed by a deductive analysis using the Endsley model.The themes emerging from the inductive analysis included environmental awareness, evolving knowledge, skill development, and applicability to practice. These aligned with the 3 levels of SA in the Endsley model in the deductive analysis suggesting that participants transformed their perception, comprehension, and projection of SA after the workshop.Simulation-based education enhanced SA perception in obstetric and neonatal emergencies for medical and nursing students in a low- and middle-income country, and the Endsley model is a feasible framework to measure learner perceived changes in SA understanding through simulation-based education.

Biofilm formation on the surfaces of indwelling medical devices has become a growing health threat due to the development of antimicrobial resistance to infection-causing bacteria. For example, ventilator-associated pneumonia caused by Pseudomonas and Staphylococci species has become a significant concern in treatment of patients during COVID-19 pandemic. Nanostructured surfaces with antifouling activity are of interest as a promising strategy to prevent bacterial adhesion without triggering drug resistance. In this study, we report a facile evaporative approach to prepare block copolymer film coatings with nanoscale topography that resist bacterial adhesion. The initial attachment of the target bacterium Pseudomonas aeruginosa PAO1 to copolymer films as well as homopolymer films was evaluated by fluorescence microscopy. Significant reduction in bacterial adhesion (93–99% less) and area coverage (>92% less) on the copolymer films was observed compared with that on the control and homopolymer films [poly(methacrylic acid) (PMAA)—only 40 and 23% less, respectively]. The surfaces of poly(styrene)-PMAA copolymer films with patterned nanoscale topography that contains sharp peaks ranging from 20 to 80 nm spaced at 30–50 nm were confirmed by atomic force microscopy and the corresponding surface morphology analysis. Investigation of the surface wettability and surface potential of polymer films assists in understanding the effect of surface properties on the bacterial attachment. Comparison of bacterial growth studies in polymer solutions with the growth studies on coatings highlights the importance of physical nanostructure in resisting bacterial adhesion, as opposed to chemical characteristics of the copolymers. Such self-patterned antifouling surface coatings, produced with a straightforward and energy-efficient approach, could provide a convenient and effective method to resist bacterial fouling on the surface of medical devices and reduce device-associated infections.

X-ray photon correlation spectroscopy (XPCS) microrheology and conventional bulk rheology were performed on silica nanoparticle dispersions associated with battery electrolyte applications to probe the properties of these specific complex materials and to explore the utility of XPCS microrheology in characterizing nanoparticle dispersions. Sterically stabilized shear-thickening electrolytes were synthesized by grafting poly(methyl methacrylate) chains onto silica nanoparticles. Coated silica dispersions containing 5-30 wt % nanoparticles dispersed in propylene carbonate were studied. In general, both XPCS microrheology and conventional rheology showed that coated silica dispersions were more viscous at higher concentrations, as expected. The complex viscosity of coated silica dispersions showed shear-thinning behavior over the frequency range probed by XPCS measurements. However, measurements using conventional mechanical rheometry yielded a shear viscosity with weak shear-thickening behavior for dispersions with the highest concentration of 30% particles. Our results indicate that there is a critical concentration needed for shear-thickening behavior, as well as appropriate particle size and surface polymer chain length, for this class of nanoparticle-based electrolytes. The results of this study can provide insights for comparing XPCS microrheology and bulk rheology for related complex fluids and whether XPCS microrheology can capture expected macroscopic rheological properties by probing small-scale particle dynamics.

Although a majority of tumors in the Cerebellopontine Angle (CPA) are vestibular schwannomas (VS), other masses can also be seen in the region and differentiation of various CPA tumors, particularly meningiomas can be difficult on imaging alone. Treatment options may vary based on specific pathology of the CPA tumor. In this study, the presence of microhemorrhage (MH) and other imaging features such as size of lesion, cystic features and pattern of IAC extension, were evaluated as a tool in distinguishing VS from other CPA masses. A review of CPA masses in the last 11 years at our institution was performed. All the pathology proven tumors with at least 1 pre-operative MRI were considered for analysis. A T2* GRE or SWI sequence was used to assess presence of MH within the lesion. Pattern of IAC extension (‘centric’ versus ‘eccentric’) of tumor was also evaluated. A total of 147 patients were reviewed out of which 102 patients (with T2* GRE or SWI) were included for analysis of MH. 57 patients (56%) had VS as the final histopathological diagnosis and 45 patients (44%) had other types of tumor. A sensitivity of 82% and a specificity of 98% was noted for the presence of MH favoring the diagnosis of VS from other tumors (p

Many recent studies have highlighted the timescale for stress relaxation of biomaterials on the microscale as an important factor in regulating a number of cell-material interactions, including cell spreading, proliferation, and differentiation. Relevant timescales on the order of 0.1–100 s have been suggested by several studies. While such timescales are accessible through conventional mechanical rheology, several biomaterials have heterogeneous structures, and stress relaxation mechanisms of the bulk material may not correspond to that experienced in the cellular microenvironment. Here we employ X-ray photon correlation spectroscopy (XPCS) to explore the temperature-dependent dynamics, relaxation time, and microrheology of multicomponent hydrogels comprising of commercial poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymer F127 and alginate. Previous studies on this system have shown thermoreversible behavior in the bulk oscillatory shear rheology. At physiological temperatures, bulk rheology of these samples shows behavior characteristic of a soft solid, with G’ > G” and no crossover between G’ and G” over the measurable frequency range, indicating a relaxation time > 125 s. By contrast, XPCS-based microrheology shows viscoelastic behavior at low frequencies, and XPCS-derived correlation functions show relaxation times ranging from 10 – 45 s on smaller length scales. Thus, we are able to use XPCS to effectively probe the viscoelasticity and relaxation behavior within the material microenvironments.

Polymers with hydrolyzable groups in their backbones have numerous potential applications in biomedicine, lithography, energy storage and electronics. In this study, acetal and ester functionalities were incorporated into the backbones of copolymers by means of alternating ring-opening metathesis polymerization catalyzed by third-generation Grubbs ruthenium catalyst. Specifically, combining large-ring (7–10 atoms) cyclic acetal or lactone monomers with bicyclo[4.2.0]oct-1(8)-ene-8-carboxamide monomers provided perfectly alternating copolymers with acetal or ester functionality in the backbones and low to moderate molecular weight distribution (Đ(M) = 1.2–1.6). Copolymers containing ester and acetal backbones hydrolyzed to significant extent under basic condition (pH 13) and acidic conditions (pH ≤ 5) respectively to yield the expected by-products within 30 hours at moderate temperature. Unlike the copolymer with all-carbon backbone, copolymers with heteroatom-containing backbone exhibited viscoelastic behavior with crossover frequency which decreases as the size of the R group on the acetal increases. In contrast, the glass transition temperature (T(g)) decreases as the size of the R group decreases. The rate of hydrolysis of the acetal copolymers was also dependent on the R group. Thus, ruthenium-catalyzed alternating ring-opening metathesis copolymerization provides heterofunctional copolymers whose degradation rates, glass transition temperatures, and viscoelastic moduli can be controlled.

Infectious eczematoid dermatitis (IED) is defined as an acute, eczematous eruption that occurs secondary to autosensitization to purulent drainage from a primary infected site. The condition is believed to develop when bacterial products, most often the result of Staphylococcal or Streptococcal species, act as haptens and stimulate an immune response. IED typically manifests as a plaque with associated vesicles and pustules surrounding drainage from a central infectious source, or as oozing, erythema, crusting, and scaling spreading peripherally from a central infectious source. Management of IED includes both targeting the causative primary infection and suppressing the immune response producing a hypersensitivity reaction. This report details two cases. Case 1 describes a common presentation of tinea pedis. Case 2 is that of a 28 year-old-male who presented with an acute onset tender, pruritic, weeping rash after wearing boots for two straight days, and who was subsequently diagnosed and treated for IED.

We utilize dynamic light scattering (DLS)-based passive microrheology to probe the dynamics and structural evolution of laponite® and laponite®-polymer glasses and dispersions at the microscale. The results reveal an increase in the dynamic heterogeneity of laponite® dispersions with an increase of laponite® concentration and aging time. In neat laponite® dispersions, the degree of stiffness is enhanced and the dynamics are retarded at higher laponite® concentration due to the formation of a repulsive glass. In the presence of PEO with a moderate molecular weight of 20 kg/mol, the microviscoelastic properties of 2 wt% laponite® dispersions show non-monotonic effects with PEO concentration upon aging, which agrees with the results obtained previously from bulk rheology. However, the magnitudes of the viscoelastic moduli (G’ and G”) of dispersions beyond the gel point obtained from DLS-microrheology is lower than that obtained from conventional rheology. Our results suggest that the DLS-microrheology can be used to qualitatively study dynamic transitions and the microviscoelastic properties of gels and soft solids.

Funding Acknowledgements Type of funding sources: None. Background Individuals with accessory pathways, also referred as the Wolff-Parkinson-White pattern (WPWp), are usually asymptomatic and fatal arrhythmias may be the first presentation. Risk stratification is recommended, with electrophysiological study (EPS) being the gold standard. Catheter ablation offers a widely available, curative option, and provides incentive for screening, particularly in high-risk populations such as athletes. Purpose We sought to assess the prevalence, real-world clinical practice and outcomes of WPWp in young individuals identified through a nationwide cardiac screening programme. Method Between 2008 and 2018, 113,209 consecutive individuals (14 to 35 years old, 38% female) underwent cardiac screening with a health questionnaire, 12-lead electrocardiogram (ECG) and cardiology consultation. Individuals with suspected cardiac disease were referred for further investigations as necessary. Clinical outcomes were obtained via an online questionnaire and matched de-identified records from the Office of National Statistics database. Individuals were classified as elite athletes, non-elite athletes and non-athletes. Results A total of 214 (0.2%) individuals were referred for secondary evaluation with a suspected WPWp (Figure 1). Clinical outcomes were unavailable for 30 (14%) individuals. Follow-up confirmed an additional 13 individuals with a WPWp who were deemed to have normal investigations at screening, of which 8 (61%) had reported cardiovascular symptoms on their HQ and, in retrospect, 4 (30%) demonstrated subtle WPWp on their ECG. A WPWp was confirmed in 187 individuals (0.2%), of which 149 (80%) individuals were considered non-athletes, 114 (61%) reported cardiovascular symptoms, 116 (62%) underwent risk stratification with an EPS and 95 (43%) underwent catheter ablation. Report of palpitation was significantly greater in non-athletes than athletes (p=0.034). In asymptomatic individuals, those engaging in sports at elite level were more likely to be referred for an EPS (p=0.04). Four adverse cardiac events were reported over a follow up period of 7.4 years (IQR 4.9 to 9.2), including 3 individuals (16 years, 20 years, 40 years) with life-threatening arrhythmic events (LAE) requiring cardioversion, and 1 individual (20 years) with sudden cardiac death. Of these 4 individuals, only 1 with a LAE had undergone risk stratification with EPS. Conclusions The incidence of SCD in this young screened population was 0.72 per 1000 person-years. Clinical practice was variable and EPS was not offered to a significant proportion of patients, despite inadequate non-invasive risk stratification. The indication to EPS was driven by the athletic status in the asymptomatic individuals. The WPW syndrome may manifest with subtle ECG changes, posing a diagnostic challenge to interpreting physicians.

Colloidal clay Laponite forms a variety of arrested states that display interesting aging behavior. Microrheology has been applied to Laponite-based glasses and gels, but few studies evaluate the influence of probe particle size. In this work, we report the dynamics and microrheology of Laponite-polymer dispersions during aging using passive microrheology with three different probe particle sizes. At early aging times, the neat Laponite dispersion forms an arrested state; the nature of this state (e.g., a repulsive glass or gel) has remained the subject of debate. The addition of polymer retards gelation and melts the arrested state. While this melting has been observed at the macroscale and has been attributed to a re-entrant transition of a repulsive glass to a liquid state, to our knowledge, it has not been observed at the microscale. The delay of the gelation time needed to form an arrested state was found to depend on the polymer concentration and could vary from ∼24 h for neat Laponite to seven days for some Laponite-polymer samples. Significant effects of probe particle sizes are observed from the mean-squared displacement (MSD) curves as small and intermediate probe particles show diffusive motion, while the motion of large particles is restricted. By examining the factor of ⟨Δ r2 (τ)⟩ a, structural heterogeneity can be confirmed through the strong size-dependence displayed. Different MSD trends of probe particles are obtained at longer aging times, but no significant changes occur after 30 days of aging. Our microrheology results also reveal significant effects of probe particle size.

We report the thermoresponsive assembly and rheology of an amphiphilic thermosensitive graft copolymer, poly(ethylene glycol)-graft-(poly(vinyl caprolactam)-co-poly(vinyl acetate)) (commercial name Soluplus®), which has been investigated for potential biomedical applications. It has received attention due to is ability to solubilize hydrophobic drugs and for its thickening behavior close to body temperature. Through use of the synchrotron at Brookhaven National Lab, and collaboration with the department of energy, the nanoscale structure and properties can be probed in greater detail. Soluplus® undergoes two structural changes as temperature is increased; the first, a concentration independent change where samples become turbid at 32 °C. Increasing the temperature further causes the formation of physically associated hydrogels. This sol-gel transition is concentration dependent and occurs at 32 °C for 40 wt% samples, and increases to 42 °C for 10 wt% samples. From variable temperature SAXS characterization micelles of 20–25 nm in radius can be seen and maintain their size and packing below 32 °C. A gradual increase in the aggregation of micelles corresponding to a thickening of the material is also observed. Close to and above the gelation temperature, micelles collapse and form a physically associated 3D network. A model is proposed to explain these physical effects, where the poly(vinyl caprolactam) group transitions from the hydrophilic corona at room temperature to the hydrophobic core as temperature is increased.

Introduction The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), otherwise known as the coronavirus (COVID-19) pandemic presents one of the greatest medical challenges of our generation. Whilst commonly causing a viral pneumonitis, myocardial damage has also been suggested by elevated serum troponin values greater than the 99th centile in up to 30% of individuals who require hospitalisation and correlates with increased mortality. Purpose We aim to identify whether transthoracic echocardiography (TTE) parameters can elucidate the phenomenon of abnormal troponin levels. Furthermore, we seek to characterise the most frequent demographic, biochemical, echocardiographic features and co-morbidities associated with adverse outcomes in this cohort. Methods A retrospective analysis was conducted utilising electronic patient records of consecutive hospitalised patients with a positive COVID-19 swab between 1st March and 31st October 2020 who underwent a TTE at our institution. Pertinent variables were collected including: the clinical indication, demographics including cardiovascular (CV) risk factors, peak troponin values and fundamental echocardiographic parameters. Results During this 8-month period, a total of 90 patients underwent a TTE. The mean age of the cohort was 63 years of age and 56% were male. More than half (56.6%) were admitted to the intensive care unit (ICU). A salient 41.1% (n=37) of our cohort succumbed to this devastating virus. Notably, 38.9% (n=35) were of black and minority ethnic origin (BAME). A striking 64.9% (n=24) of patients who died had hypertension. The mean troponin levels were 168.7 ng/L and 176.6 ng/L (0–34 ng/L) in the survivors and non-survivors group respectively. With regards to TTE, the left ventricular parameters were similar between both groups with a mean left ventricular ejection fraction (LVEF) of 60.6% in the non-survivors. Conversely, both right ventricular (RV) dysfunction (37.8%) and raised pulmonary artery systolic pressures (PASP) (51.4%) were markedly more frequent in the patients who perished due to COVID-19 infection. Conclusion Remarkably, in this extremely ill group of patients who died, 91.9% of patients had a preserved LVEF. There were no overt differences between troponin levels in the survivors and non-survivors. However, hypertension, RV dysfunction and raised PASP were distinctly more prominent in the non-survivors. Thus, providing insight that a normally functioning left ventricle does not preclude to poor outcomes. Overall, this single-centre retrospective study demonstrates that the echocardiographic phenotype associated with mortality is consistent with a severe respiratory illness rather than direct myocardial injury from COVID-19. A multi-modality imaging approach may facilitate the identification of adverse tissue characterisation changes associated with this novel virus as well as guiding further risk stratification and patient management on a case-by-case basis. Funding Acknowledgement Type of funding sources: None.

Background: PCOS is one of the most common endocrine metabolic disorder found among women of reproductive age group. It is characterized by the presence of ovulatory dysfunction, hyperandrogenism, and polycystic ovarian morphology. PCOS has seen to have overlapping features of metabolic syndrome and insulin resistance, which seems to be a linking factor between the two. The present study was undertaken to nd the prevalence of metabolic syndrome and Insulin resistance in women diagnosed with PCOS in north-Indian population. Objective:To nd the prevalence of metabolic syndrome and insulin resistance among women diagnosed with PCOS in north-Indian population. Materials and Methods: 100 women attending gynecology-OPD diagnosed with PCOS were enrolled and assessed for the presence of clinical and/or biochemical features of metabolic syndrome. Results: Metabolic syndrome was present in 31% of women with PCOS. 87% of women with metabolic syndrome were obese, 93.5% had HDL level

We assessed the diagnostic yield and costs of an electrocardiogram-based national screening programme in elite cricket players and the incremental value of transthoracic echocardiography and periodic evaluation.Cross-sectional study.Between 2008 and 2019, 1208 cricketers underwent screening with a health questionnaire, 12-lead electrocardiogram and cardiology consultation. Athletes with concerning findings underwent on-site transthoracic echocardiography and further investigations as necessary. In addition, despite a normal health questionnaire and electrocardiogram, 342 (28.3%) athletes had a transthoracic echocardiogram and 493 (40.8%) underwent repeat evaluations.After initial evaluation, 47 (3.9%) athletes underwent on-site transthoracic echocardiography of whom 35 (2.8%) were referred for further evaluation. Four athletes (0.3%) were diagnosed with major cardiac conditions; hypertrophic cardiomyopathy (n = 1), arrhythmogenic cardiomyopathy (n = 1) and Wolff-Parkinson-White pattern (n = 2). Two athletes were identified with minor valvular abnormalities. Repeat evaluation of 493 athletes identified hypertrophic cardiomyopathy in a 22-year-old athlete, two years after his initial normal screening. During a follow-up of 5.8 ± 2.9 years no additional diagnoses or adverse cardiac events were reported. The cost of the electrocardiogram-based programme was £127,844, translating to £106 per athlete and £25,569 per major cardiac condition identified.Routine transthoracic echocardiography in 342 athletes identified two athletes with major cardiac conditions (bicuspid aortic valve with severe aortopathy and aortic regurgitation and an atrial septal defect associated with right ventricular volume overload) and 10 athletes with minor abnormalities.An electrocardiogram-based national screening programme identified a major cardiac condition in 0.3% of athletes. Routine transthoracic echocardiography and periodic evaluation increased the diagnostic yield to 0.6%, at an incremental cost.

Funding Acknowledgements Type of funding sources: None. Background The apical variant of hypertrophic cardiomyopathy (ApHCM) has male predominance and is a relatively rare phenotype in Western population. Characteristics of female and black patients diagnosed with ApHCM are very limited in the existing literature. Purpose We aimed to investigate whether gender and race are associated with a different clinical presentation and CMR findings in apical HCM. Methods We retrospectively analysed 150 patients (113 males and 37 females) with a diagnosis of apical HCM who have been followed in our inherited cardiac conditions (ICC) clinic between 2010 and 2020. Only patients with a CMR study and apical hypertrophy defined as ≥ 13mm at the time of diagnosis were included. Demographics and clinical characteristics were obtained from electronic records. Volumetric CMR data were taken from confirmed reports while other parameters were measured by standard protocol. "Pure" ApHCM was defined as isolated apical hypertrophy and "mixed" with both apical and septal hypertrophy but with the apex thickest (1). Apical displacement of papillary muscles (PM) was defined when the base of PM originated from the apical one-third of the left ventricle (LV) in the apical 4- or 2-chamber views. Giant T-wave inversion was defined as T-wave inversion that is equal or greater than 10 mm (1 mV) in any electrocardiogram lead. Results Our study population included patients of White (55, 37%), Black (37, 25%), Asian (36, 24%) and Mixed/Others (22, 15%) ethnicity. Black patients were more likely to have a diagnosis of hypertension at presentation when compared to White (70% vs 40%, p = 0.01) and to Asian and Mixed/Other patients (70% vs 48%, p = 0.03). Similarly, they were more likely to have "mixed" ApHCM than White (49% vs 20%, p = 0.003) and Asian and Mixed/Other (49% vs 26%, p = 0.02) patients. Females were diagnosed at an older age (63 ± 12 vs 52 ± 14, p Conclusions In our cohort, females with ApHCM presented at an older age and were less likely to have giant T-wave inversion on ECG. Black patients with ApHCM were more likely to have hypertension and the "mixed" type of the disease.

Previous studies have demonstrated that films of sequence-controlled amphiphilic copolymers display contact angles that depend on microblock size. This suggests that microblock length may provide a means of tuning surface and interfacial properties. In this work, the interfacial rheology of a series of sequence-controlled copolymers, prepared through the addition of bicyclo[4.2.0]oct-1(8)-ene-8-carboxamide (monomer A) and cyclohexene (monomer B) to generate sequences up to 24 monomeric units composed of (A

PURPOSE/OBJECTIVE(S) Women living with HIV are at an increased risk of acquiring HPV-related cervical atypia that can progress to cervical cancer. In sub-Saharan Africa, cervical cancer makes up the largest proportion of years of life lost due to cancer, largely due to women diagnosed at younger ages, typically between 35 and 50 years. Botswana has the second highest prevalence of HIV in the world. Current World Health Organization guidelines for cervical cancer recommend screening between ages of 30-49 years; however, data suggest that women with HIV who get cervical cancer are diagnosed at a younger age. We assessed characteristics of women diagnosed with cervical cancer to further inform and refine screening guidelines. MATERIALS/METHODS We prospectively enrolled women diagnosed with cervical cancer from January 2015 to March 2020 at two tertiary hospitals in Gaborone, Botswana. We performed chi-square and ANOVA analyses to evaluate the association between categorical age at diagnosis and HIV status, CD4 count, viral load and other sociodemographic and clinical factors. RESULTS Data were available for 1,130 women who were diagnosed with cervical cancer, 69.3% were women living with HIV (WLWH). Of the total 1130 women (median age 47.9 (IQR 41.2-59.1), 1.3 % were < 30 years of age, 19.1 % were 30-39 and 37.2% were 40-49. Overall, 20.4% (n = 231) of cancers were in women < 40 years. When analyzed by age, 86.7% of patients < 30 years of age were WLWH (mean CD4 371.6 cells/µL), 86.1% in patients 30-39 years (mean CD4 671.8 cells/µL). Overall, 86.1% of women who were < 40 years of age were WLWH compared to 64.9% of women who were ≥40 years old (P < 0.001). Mean CD4 counts for WLH who were < 40 years was 655.10 cells/µL and 18.2% had detectable viral load, while mean CD4 count for ≥40 years was 619.58 cells/µL with 23.8% having a detectable viral load. The most common FIGO stage of presentation in patients < 40 years was stage II (39.9%) compared to stage III (39.7%) in ≥40-year-old women (P = 0.08). Over three quarters (84.0%) of women < 40 years old were single compared to 60.8 % in those ≥40 years. Among women < 40 years old who were screened for cervical cancer, 87.4% (n = 111) were WLHV, and among women ≥40 years 70.5% (n = 308) were WLHV. Women < 40 years were more likely to have ever been screened than women ≥40 years old (59.1% vs 50.7%, P = 0.03). CONCLUSION Age of cervical cancer diagnosis may be younger in countries with higher prevalence of HIV, like Botswana. Approximately 20% of the patients present with cancer < 40 years of age and should have been screened 10 years prior to cancer diagnosis to prevent cancer. However, these patients will not be screened per the current WHO screening guidelines. Changing international cervical cancer screening guidelines to women at younger ages than 30-49 years should be urgently considered especially in setting with high prevalence of HIV. Furthermore, engaging women without HIV in screening programs is critical for cervical cancer elimination.

Purpose/Objective(s) Polyethylene glycol hydrogel has increasingly been used in brachytherapy for organ-at-risk sparing. This study evaluated visualization and dosimetry with hydrogel in gynecologic brachytherapy. Materials/Methods Women with gynecologic cancer received hydrogel injection prior to brachytherapy on a prospective clinical trial. Two researchers rated the appearance immediately after hydrogel injection and measured volume at initial injection, and at 3 and 6 months follow-up on T2w MRI. Visualization was rated as: (1) not visualized; (2) faint or trace visibility (shadow or haze); (3) visible but indistinct borders (definable entity, not just haze); (4) partially distinct border, partial haze; and (5) clearly visualized, unequivocal. Cohen's Kappa statistic assessed interobserver variability. For patients that had spacer injected during the second implant of brachytherapy, EQD2 rectal D2cc and CTVHR D90 absolute and ratio values were calculated between the first and second implants to determine the difference in dose to tumor after placement of hydrogel. A paired t-test was performed. Results 28 women were enrolled and had an average patient age of 57.2 years (38-77). Brachytherapy applicators used in treatment included the Syed (33.3%, n = 9), Tandem and Ring (29.6%, n = 8), and Syed and Tandem (37.04%, n = 11). Diagnoses included cervical cancer (57.1%, n = 16), vaginal (23.4%, n = 6), endometrial (17.9%, n = 5), and urethral cancer (3.6%, n = 1). The average rating of hydrogel amount was 3.4/5, and did not differ by type of applicator used or by diagnosis. Inter-rater reliability (kappa statistic) for the 2 readers on the 5-point scale was 0.37. Average hydrogel volumes on 3 and 6 month T2 MRIs were 69.3 ± 53.4% and 43.7 ± 34.2%, relative to day of injection. Five patients had spacer placed at the time of the second fraction, and when compared to the first fraction, the EQD2 CTVHR D90 increase (per fraction) was 1.43 Gy10 (P = 0.006) and the average reduction in rectum EQD2 D2cc dose to the rectum was 0.39 Gy3 (P = 0.34) per fraction. The rectum EQD2 D2cc to CTVHR D90 ratio decreased from 0.65 to 0.49, on average, after hydrogel injection. Conclusion Hydrogel demonstrated moderate inter-rater reliability and progressive decrease in size over 6 months on MRI. There was a significant increase in D90 and decrease in the ratio of rectal D2cc/D90 after hydrogel injection in those that had first (without) and second (with hydrogel) fraction comparative implants. Author Disclosure M. Morcos: None. R. Bhatia: None. K. Li: None. A.N. Viswanathan: Research Grant; National Cancer Institute. Honoraria; NCI Uterine Cancer Task Force Chair.

The canonical binding site on the B subunit of cholera toxin (CTB) binds to GM1 gangliosides on host cells. However, the recently discovered noncanonical binding site on CTB with affinity for fucosylated molecules has raised the possibility that both sites can be involved in initiating intoxication. Previously, we showed that blocking CTB binding to human and murine small intestine epithelial cells can be increased by simultaneously targeting both binding sites with multivalent norbornene-based glycopolymers [ACS Infect. Dis. 2020, 6, 5, 1192–1203]. However, the mechanistic origin of the increased blocking efficacy was unclear. Herein, we observed that mixing CTB pentamers and glycopolymers that display fucose and galactose sugars results in the formation of large aggregates, which further inhibits binding of CTB to human granulocytes. Dynamic light scattering analysis, small-angle X-ray scattering analysis, transmission electron microscopy, and turbidimetric assays revealed that the facial directionality of CTB promotes interchain cross-linking, which in turn leads to self-assembly of protein–polymer networks. This cross-linking-induced self-assembly occurs only when the glycopolymer system contains both galactose and fucose. In an assay of the glycopolymer’s ability to block CTB binding to human granulocytes, we observed a direct correlation between IC(50) and self-assembly size. The aggregation mechanism of inhibition proposed herein has potential utility for the development of low-cost macromolecular clinical therapeutics for cholera that do not have exotic architectures and do not require complex synthetic sequences.

A series of ionic amphiphilic alternating copolymers were characterized via SAXS, TEM and DLS to help understand factors that could potentially affect self-assembly, including the degree of polymerization, the length of hydrophobic spacers between ionic units, the distance between charged groups and polymer backbone, solvent envrioment and counterions.

Rationale: Surgery results in rapid and progressively severe exposure of tumor tissue to hypoxia, up to the point of complete removal, but its effect on tumor gene expression is not well characterized. We document the molecular effects of surgery on primary breast cancer tumor with a serial tissue sampling strategy, including an intra-operative sample. Methods: We included treatment naïve, non-metastatic breast cancer patients and sampled tumor and tumour adjacent normal tissue during surgery at three time points: beginning of surgery (Sample A), after half the tumor circumference had been devascularized (Sample B) and from completely resected tumor (Sample C). Patients were divided into two groups: discovery and validation. Tumor or adjacent normal samples from the discovery group underwent whole transcriptome paired-end sequencing (RNA-Seq) generating at least 50 million reads using next generation sequencing. Findings from discovery group were evaluated in a validation group using qRT-PCR and Nanostring nCounter gene expression profiling. Results: 81 breast cancer patients were eligible for this study of whom 46 with at least 1 quality passed sample at time-point A, B or C comprised the discovery group whose samples underwent RNA-seq. Validation group comprised two subsets: 35 independent patients (8 patients’ samples qRT-PCR, data included here; 27 patients’ samples nCounter gene expression, data will be presented) and 17 patients from discovery group whose samples also underwent nCounter gene expression profiling (data will be presented). Individual patient based analyses for A vs B vs C in discovery group revealed 249 significantly de-regulated genes in at least 20% of patients, in at least one comparison (AvB or BvC or AvC). Genes involved in stress response (FOSB, FOS, JUN, JUNB, DUSP1, CYR61, EGR1-3, ATF3, RGS1, RGS2), inflammation (IL20, IL8, SOCS3, GABRP, PIGR, NR4A1-2, CCL2- 3, CCL21, CCL14, CCL18-19, CXCL2, CXCL9-10, CXCL14), invasion & migration (PTGS2, MMP9-13), lipid metabolism (CD36, LIPE, TAT, FABP4, PLIN1, PLIN4, LPL, LEP), epithelial markers (KRT5, KRT7, KRT14-17, KRT23, KRT6A-6B) and cellular differentiation(SOX10, LRP2, S100A2, S100A7-A9, S100B, S100P) were significantly deregulated at time-point B versus A and many of these genes were also significantly deregulated in C versus A comparison, suggesting sustained deregulation through surgical resection. Replicative analysis involving comparison of tumors grouped by time points (A vs B vs C) identified 192 genes uniquely de-regulated in any one of the 3 comparisons, of which 42 overlapped with patient-wise analysis. These 42 genes included all the AP-1 transcription factor network signaling genes, epithelial markers (KRT14, KRT6A), inflammation related genes (SOCS3, PIGR, GABRP, NR4A1, NR4A2), lipid metabolism related genes (PLIN1) and cellular differentiation & cell fate related genes (SOX10, LRP2). Pathway analyses will be presented. qRT-PCR on paired samples in 8 independent patients validated the differential expression of eight genes in either AvB or AvC or both comparisons: FOS, FOSB, JUNB, DUSP1, RGS1, NR4A2, ZFP36, andMMP13. Comparison of biopsy (corresponding to A) with surgical samples (corresponding to C) in 6 cancer types (breast, cervical, lymphoma, mesothelioma, esophageal and sarcoma) in TCGA studies showed statistically significant de-regulation of 11 AP-1 transcription factor network signaling related genes in at least 4 cancers, further validating our experimental results. Conclusions: Our experiment, uniquely including an intra-operative tumor sample, shows that surgical removal induces a conserved stress response in the primary tumor that is potentially capable of bestowing metastatic capability on the tumor cells. Citation Format: Sudeep Gupta, Rohan Chaubal, Nilesh Gardi, Sunil Pachakar, Dimple Bhatia, Poonam Gera, Nita Nair, Shalaka Joshi, Vani Parmar, Purvi Thakkar, Garvit Chitkara, Rasika Kadam, Sejal Gujarathi, Harsh Oza, Rohini Hawaldar, Vaibhav Vanmali, Kenneth Buetow, Amit Dutt, Rajendra Badwe. Molecular effects of surgical resection on primary breast tumor [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-05-01.