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Anh Trung Nguyen,1,2 Hai Quang Pham,3,4 Thanh Xuan Nguyen,1,2,5 Thu Thi Hoai Nguyen,1,2 Huong Thi Thu Nguyen,1,2 Tam Ngoc Nguyen,1,2 Dung Thi Kim Dinh,1 Hai Thanh Phan,3,4 Son Hoang Nguyen,6 Bach Xuan Tran,7,8 Carl A Latkin,8 Roger CM Ho,9,10 Cyrus SH Ho,9 Thang Pham,1,2 Huyen Thi Thanh Vu1,2 1Hanoi Medical University, Hanoi, Vietnam; 2National Geriatric Hospital, Hanoi, Vietnam; 3Institute for Global Health Innovations, Duy Tan University, Da Nang, Vietnam; 4Faculty of Medicine, Duy Tan University, Da Nang 550000, Vietnam; 5Dinh Tien Hoang Institute of Medicine, Hanoi, Vietnam; 6Center of Excellence in Health Services and System Research, Nguyen Tat Thanh University, Ho Chi Minh, Vietnam; 7Institute for Preventive Medicine and Public Health, Hanoi Medical University, Hanoi 100000, Vietnam; 8Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA; 9Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; 10Institute for Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore, SingaporeCorrespondence: Huyen Thi Thanh VuDepartment of Geriatrics, Hanoi Medical University, 01 Ton That Tung, Hanoi, VietnamTel +84 913531579Email vuthanhhuyen11@hmu.edu.vnBackground: Diabetes-related complications have become increasingly prevalent and complicated to manage, especially among frail older adults with co-morbidities, poor physical function, and impaired cognition. Thus, knowledge, attitude, and practice (KAP) of elderly diabetic patients play an essential role in controlling the disease and its complications.Patients and Methods: A cross-sectional study was conducted on 176 diabetic patients at the outpatient clinics, National Geriatric Hospital, Hanoi, Vietnam from August to November 2015. Patients’ knowledge, attitude, and practice regarding diabetes mellitus were assessed using a structured questionnaire. Exploratory factor analysis and multivariate Tobit regression model were used to identify factors associated with knowledge, attitude, practice about diabetes mellitus.Results: Of 176 diabetic patients, patients’ knowledge was divided into two main groups: “Diabetes definition and management” (mean score = 57.7 ± 25.6) and “Targets for diabetic control” (mean score = 66.1 ± 30.4). Patients scored high points of attitudes toward diabetes severity and its complications (mean score = 95.8 ± 13.0); however, knowledge and practice scores were only moderate (mean score = 68.1 ± 16.8). There were only 8.5% of people having daily self-blood glucose monitoring. Advanced age, low educational level, rural area, and duration of diabetes less than 5 years were negative associated with knowledge, attitude, and practice regarding diabetes mellitus. This study also shows that frailty and co-morbidities/diabetic complications could impair patients’ knowledge.Conclusion: Older patients with diabetes had high levels of perceived severity attitudes on diabetes mellitus. However, the knowledge and practice levels were still inadequate. Pragmatic diabetic health literacy, counseling and education programs, as well as home-based treatments are viable options to improve health outcomes.Keywords: attitude, diabetes, elderly, knowledge, practice

Background Prosthesis-patient mismatch (PPM) is characterised by the effects of inadequate prosthesis size relative to body surface area (BSA). It is uncertain whether PPM after mitral valve replacement impacts upon clinical outcome. This was examined in an Australian population. Methods From 2001 to 2009, 1006 mechanical and bioprosthetic mitral valves were implanted across 10 institutions. Effective orifice areas (EOA) were obtained from a literature review of in vivo echocardiographic data. Absent, moderate and severe PPM was defined as an indexed EOA (EOA/BSA) of >1.20cm(2)/m(2), >0.90 to <=1.20cm(2)/m(2) and <=0.9cm(2)/m(2), respectively. Early outcomes and 7-year survival were compared between these three groups. Results PPM was absent in 34%, moderate in 53% and severe in 13% of patients. Patients with PPM were more likely to be male (42% vs 52% vs 62%, p<0.0001) and obese (14% vs 20% vs 56%, p<0.0001). Postoperatively there was similar 30-day mortality (5% vs 5% vs 6%, p=0.83) and early any mortality/morbidity (24% vs 27% vs 29%, p=0.40). Seven-year survival was similar between groups (72±4.1% vs 76±3.2% vs 69±10.3%, p=0.76). PPM did not predict adverse events after logistic and Cox regressions with and without propensity score adjustment. Subgroup analyses of those with isolated mitral valve surgery, patients with preoperative congestive heart failure and non-obese patients failed to show an association between PPM and mid-term mortality. Conclusions Overall, PPM was not associated with poorer early outcomes or mid-term survival. Oversizing valves may be technically hazardous and do not yield superior outcomes. Easier implantation by appropriate sizing appears justified. [ABSTRACT FROM AUTHOR]

Routine monitoring of performance in the provision of cardiac services aids quality assurance and enables comparisons of performance to national and international standards. The Australasian Society of Cardiac and Thoracic Surgeons conducts a surgical registry that has grown from six hospitals participating in 2001 to 21 contributing in 2010. Variation in performance is monitored on a quarterly basis through the use of control chart methodology, and a peer-review mechanism and governance process for reporting have been established. Proposed future developments of the registry include its expansion to include interventional cardiology procedures, such as implantation of stents and cardiac devices, and a modular format, with the patient rather than the procedure being the key element of the system. An Australian Cardiac Procedures Registry will provide information to stakeholders, including consumers, clinicians, health funders and policymakers, on performance standards and quality of care of medical services affecting an ever-increasing number of Australians. [ABSTRACT FROM AUTHOR]

The primary goals of this study were to investigate the formation of abasic sites (AP sites) induced by methyl methanesulfonate (MMS) and hydrogen peroxide (H 2 O 2 ), and to characterize specific types of these pro-mutagenic DNA lesions in calf thymus DNA (CT-DNA), and BEAS-2B human lung normal cell line. Furthermore, these profiles were compared with those observed in leukocytes derived from healthy controls (HC), breast cancer patients (BCP) before treatment, and 5-year survivors. Results indicated that both H 2 O 2 and MMS induced the concentration- and time-dependent formation of AP sites in CT-DNA. To characterize the specific types of AP sites induced by H 2 O 2 or MMS, we performed AP site cleavage assay using putrescine, T7 exonuclease (T7 Exo), and exonuclease III (Exo III). Results showed that the AP sites induced by H 2 O 2 in CT-DNA were predominantly 5'-and 3'-nicked AP sites and no intact AP sites were detected. By contrast, the majority of AP sites generated by MMS in CT-DNA are not excisable and are classified as residual and intact AP sites. Similar approaches were performed in human BEAS-2B cells and comparable observations were confirmed in the cell-based model. Further investigation indicated that the profile of the AP sites observed in Taiwanese HC is identical to that of BEAS-2B cells treated with H 2 O 2 whereas the pattern of AP sites detected in BCP is similar to that of CT-DNA exposed to H 2 O 2 , suggesting that these AP sites were produced primarily through reactive oxygen species (ROS) generation. More than 70 % of the AP sites in leukocytes derived from BCP were 5'-nicked and residual AP sites. Furthermore, the characteristics of the AP sites detected in 5-year survivors are comparable with the ones in HC by using putrescine cleavage assay. Overall, we speculate that deficiency in the DNA repair cascade may play a role in mediating the formation of specific types of AP sites detected in BCP., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Po-Hsiung Lin reports financial support was provided by National Science and Technology Council. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Collagen fiber architecture within the skeletal muscle extracellular matrix (ECM) is significant to passive muscle mechanics. While it is thought that collagen fibers re-orient themselves in response to changes in muscle length, this has not been dynamically visualized and quantified within a muscle. The goal of this study was to measure changes in collagen alignment across a range of muscle lengths and compare the corresponding alignment to muscle mechanics. We hypothesized that collagen fibers dynamically increase alignment in response to muscle stretching, and this change in alignment is related to passive muscle stiffness. Further, we hypothesized that digesting collagen fibers with collagenase would reduce the re-alignment response to muscle stretching. Using DBA/2J and D2.mdx mice, we isolated extensor digitorum longus (EDL), soleus, and diaphragm muscles for collagenase or sham treatment and decellularization to isolate intact or collagenase-digested decellularized muscles (DCMs). These DCMs were mechanically tested and imaged using second harmonic generation microscopy to measure collagen alignment across a range of strains. We found that collagen alignment increased in a strain-dependent fashion, but collagenase did not significantly affect the strain-dependent change in alignment. We also saw that the collagen fibers in the diaphragm epimysium (surface ECM) and perimysium (deep ECM) started at different angles, but still re-oriented in the same direction in response to stretching. These robust changes in collagen alignment were weakly related to passive DCM stiffness. Overall, we demonstrated that the architecture of muscle ECM is dynamic in response to strain and is related to passive muscle mechanics. STATEMENT OF SIGNIFICANCE: Our study presents a unique visualization and quantification of strain-induced changes in muscle collagen fiber alignment as they relate to passive mechanics. Using dynamic imaging of collagen in skeletal muscle we demonstrate that as skeletal muscle is stretched, collagen fibers re-orient themselves along the axis of stretch and increase their alignment. The degree of alignment and the increase in alignment are each weakly related to passive muscle stiffness. Collagenase treatments further demonstrate that the basis for muscle Extracellular matrix stiffness is dependent on factors beyond collagen crosslinking and alignment. Together the study contributes to the knowledge of the structure-function relationships of muscle extracellular matrix to tissue stiffness relevant to conditions of fibrosis and aberrant stiffness., Competing Interests: Conflict of Interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced that work reported in this manuscript., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Study Question: Is oocyte developmental competence associated with changes in granulosa cell (GC) metabolism?, Summary Answer: GC metabolism is regulated by the LH surge, altered by obesity and reproductive aging, and, in women, specific metabolic profiles are associated with failed fertilization versus increased blastocyst development., What Is Known Already: The cellular environment in which an oocyte matures is critical to its future developmental competence. Metabolism is emerging as a potentially important factor; however, relative energy production profiles between GCs and cumulus cells and their use of differential substrates under normal in vivo ovulatory conditions are not well understood., Study Design, Size, Duration: This study identified metabolic and substrate utilization profiles within ovarian cells in response to the LH surge, using mouse models and GCs of women undergoing gonadotropin-induced oocyte aspiration followed by IVF/ICSI., Participants/materials, Setting, Methods: To comprehensively assess follicular energy metabolism, we used real-time metabolic analysis (Seahorse XFe96) to map energy metabolism dynamics (mitochondrial respiration, glycolysis, and fatty acid oxidation) in mouse GCs and cumulus-oocyte complexes (COCs) across a detailed time course in the lead up to ovulation. In parallel, the metabolic profile of GCs was measured in a cohort of 85 women undergoing IVF/ICSI (n = 21 with normal ovarian function; n = 64 with ovarian infertility) and correlated with clinical parameters and cycle outcomes., Main Results and the Role of Chance: Our study reveals dynamic changes in GC energy metabolism in response to ovulatory LH, with mitochondrial respiration and glycolysis differentially affected by obesity versus aging, in both mice and women. High respiration in GCs is associated with failed fertilization (P < 0.05) in a subset of women, while glycolytic reserve and mitochondrial ATP production are correlated with on-time development at Day 3 (P < 0.05) and blastocyst formation (P < 0.01) respectively. These data provide new insights into the cellular mechanisms of infertility, by uncovering significant associations between metabolism within the ovarian follicle and oocyte developmental competence., Limitations, Reasons for Caution: A larger prospective study is needed before the metabolic markers that were positively and negatively associated with oocyte quality can be used clinically to predict embryo outcomes., Wider Implications of the Findings: This study offers new insights into the importance of GC metabolism for subsequent embryonic development and highlights the potential for therapeutic strategies focused on optimizing mitochondrial metabolism to support embryonic development., Study Funding/competing Interest(s): National Health and Medical Research Council (Australia). The authors have no competing interests., Trial Registration Number: N/A., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Lipid droplets (LDs) are spherical organelles that localize in the cytosol of eukaryotic cells. Different proteins are embedded on the surface of LDs, so LDs play a vital role in the physiological activities of cells. The dysregulation of LDs is associated with various human diseases, such as diabetes and obesity. Therefore, it is essential to develop a fluorescent dye that labels LDs to detect and monitor illnesses. In this study, we developed the compound BDAA12C for staining LDs in cells. BDAA12C exhibits excellent LD specificity and low toxicity, enabling us to successfully stain and observe the fusion of LDs in A549 cancer cells. Furthermore, we also successfully distinguished A549 cancer cells and MRC-5 normal cells in a co-culture experiment and in normal and tumour tissues. Interestingly, we found different localizations of BDAA12C in well-fed and starved A549 cancer cells and consequently illustrated the transfer of fatty acids (FAs) from LDs to mitochondria to supply energy for β-oxidation upon starvation. Therefore, BDAA12C is a promising LD-targeted probe for cancer diagnosis and tracking lipid trafficking within cells., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Acute coronary syndrome (ACS) admissions and percutaneous coronary intervention (PCI) volume declined during periods of COVID-19 lockdown internationally in 2020. The effect of lockdown on emergency medical service (EMS) utilisation, and PCI volume during the initial phase of the pandemic in Australia has not been well described., Method: We analysed data from the Victorian Cardiac Outcomes Registry (VCOR), a state-wide PCI registry, linked with the Ambulance Victoria EMS registry. PCI volume, 30-day major adverse cardiovascular and cerebrovascular events (MACCE; composite of mortality, myocardial infarction, stent thrombosis, unplanned revascularisation, and stroke), and EMS utilisation were compared over four time periods: lockdown (26 Mar 2020-12 May 2020); pre-lockdown (26 Feb 2020-25 Mar 2020); post-lockdown (13 May 2020-10 Jul 2020); and the year prior (26 Mar 2019-12 May 2019). Interrupted time series analysis was performed to assess PCI trends within and between consecutive periods., Results: The EMS utilisation for ACS during lockdown was higher compared with other periods: lockdown 39.4% vs pre-lockdown 29.7%; vs post-lockdown 33.6%; vs year prior 27.1%; all p<0.01. Median daily PCI cases were similar: 31 (IQR 10, 38) during lockdown; 39 (15, 49) pre-lockdown; 39.5 (11, 44) post-lockdown; and, 42 (10, 49) the year prior; all p>0.05. Median door-to-procedure time for ACS indication during lockdown was shorter at 3 hours (1.2, 20.6) vs pre-lockdown 3.9 (1.7, 21); vs post-lockdown 3.5 (1.5, 21.26); and, the year prior 3.5 (1.5, 23.7); all p<0.05. Lockdown period was associated with lower odds for 30-day MACCE compared to pre-lockdown (odds ratio [OR] 0.55 [0.33-0.93]; p=0.026); post-lockdown (OR 0.66; [0.40-1.06]; p=0.087); and the year prior (OR 0.55 [0.33-0.93]; p=0.026)., Conclusions: Contrary to international trends, EMS utilisation for ACS increased during lockdown but PCI volumes remained similar throughout the initial stages of the pandemic in Victoria, with no observed adverse effect on 30-day MACCE during lockdown. These data suggest that the public health response in Victoria was not associated with poorer quality cardiovascular care in patients receiving PCI., Competing Interests: Conflicts of Interest The authors have no conflicts of interest to report., (Copyright © 2024 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Background: Short harvested right renal veins (RV) are quite common in living donor kidney transplantation (KT). This technical difficulty might interfere implanting and increase warm ischemic time. Several techniques to overcome this problem have been applied, including iliac vein transposition, inverted transplant, synthetic graft, saphenous vein… Application of accompanying gonadal vein (GV), which is easily approachable and less time-consuming, has been recently published. This study aims to evaluate its effectiveness and safety., Methods: Retrospective study on KT using the gonadal vein to lengthen the short right renal vein at Viet Duc University Hospital from April 2019 to April 2022. The following data were gathered: baseline characteristics, vascular imaging in CT scan/after nephrectomy and after reconstruction (mm), reconstruction and surgical time, hospitalization days. The outcomes were determined by kidney function after transplantation (plasma creatinine, creatinine clearance) and related complications., Results: Twenty-five cases with procured right kidney with short RV from the living donor which were reconstructed and lengthened by the accompanying GV were collected. The additional length of RV was 15.9 ± 2.4 mm. Average cold ischemic time, venoplasty time, warm ischemic time were 60.4 ± 8.2, 21.2 ± 5.3, and 38.1 ± 5.6 min, respectively. The average hospital stay was 15.3 ± 3.2 days. Average follow-up time was 31 ± 5.2 months, creatinine clearance was around 60 ml/min after 1 year, no vascular or urologic complications was observed., Conclusion: Accompanying GV from a living donor to lengthen short right RV in KT is a feasible, safe, and effective technique., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: We aim to describe prevalence of Emergency Medical Service (EMS) use, investigate factors predictive of EMS use, and determine if EMS use predicts treatment delay and mortality in our ST-elevation myocardial infarction (STEMI) cohort., Method: We prospectively collected data on 5,602 patients presenting with STEMI for primary percutaneous coronary intervention (PCI) transported to PCI-capable hospitals in Victoria, Australia, from 2013-2018 who were entered into the Victorian Cardiac Outcomes Registry (VCOR). We linked this dataset to the Ambulance Victoria and National Death Index (NDI) datasets. We excluded late presentation, thrombolysed, and in-hospital STEMI, as well as patients presenting with cardiogenic shock and out-of-hospital cardiac arrest., Results: In total, 74% of patients undergoing primary PCI for STEMI used EMS. Older age, female gender, higher socioeconomic status, and a history of prior ischaemic heart disease were independent predictors of using EMS. EMS use was associated with shorter adjusted door-to-balloon (53 vs 72 minutes, p<0.001) and symptom-to-balloon (183 vs 212 minutes, p<0.001) times. Mode of transport was not predictive of 30-day or 12-month mortality., Conclusions: EMS use in Victoria is relatively high compared with internationally reported data. EMS use reduces treatment delay. Predictors of EMS use in our cohort are consistent with those prevalent in prior literature. Understanding the patients who are less likely to use EMS might inform more targeted education campaigns in the future., Competing Interests: Disclosures AB is supported by a University of Melbourne Research Training Program Scholarship. DS is supported by an Australian National Heart Foundation grant. ZN is supported by a National Health and Medical Research Council (NHMRC) Early Career Fellowship (#1146809). CMR is supported by an NHRMC Principal Research Fellowship (GNT 1136372). EA is supported by an NHRMC Postgraduate Scholarship (#2003449). The remaining authors report no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: There is increasing awareness that patients without standard modifiable risk factors (SMuRFs; diabetes, hypercholesterolaemia, hypertension and smoking) may represent a unique subset of patients with acute coronary syndrome (ACS). We aimed to investigate the prevalence and outcomes of patients with SMuRF-less ACS undergoing percutaneous coronary intervention (PCI) compared with those with SMuRFs., Methods: We analysed data from the Melbourne Interventional Group PCI Registry. Patients with coronary artery disease were excluded. The primary outcome was 30-day mortality. Secondary outcomes included in-hospital and 30-day events. Long-term mortality was investigated using Cox-proportional hazards regression., Results: From 1 January 2005 to 31 December 2020, 2727/18 988 (14.4%) patients were SMuRF less, with the proportion increasing over time. Mean age was similar for patients with and without SMuRFs (63 years), and fewer females were SMuRF-less (19.8% vs 25.4%, p<0.001). SMuRF-less patients were more likely to present with cardiac arrest (6.6% vs 3.9%, p<0.001) and ST-elevation myocardial infarction (59.1% vs 50.8%, p<0.001) and were more likely to experience postprocedural cardiogenic shock (4.5% vs 3.6%, p=0.019) and arrhythmia (11.2% vs 9.9%, p=0.029). At 30 days, mortality, myocardial infarction, revascularisation and major adverse cardiac and cerebrovascular events did not differ between the groups. During median follow-up of 7 years, SMuRF-less patients had an adjusted 13% decreased rate of mortality (HR 0.87 (95% CI 0.78 to 0.97))., Conclusions: The proportion of SMuRF-less patients increased over time. Presentation was more often a devastating cardiac event compared with those with SMuRFs. No difference in 30-day outcomes was observed and SMuRF-less patients had lower hazard for long-term mortality., Competing Interests: Competing interests: The Melbourne Interventional Group acknowledges funding from Abbott Vascular, AstraZeneca, Bristol Myers Squibb, Medtronic, and Pfizer. These companies do not have access to data and do not have the right to review manuscripts or abstracts before publication., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Suboptimal coronary reperfusion (no reflow) is common in acute coronary syndrome percutaneous coronary intervention (PCI) and is associated with poor outcomes. We aimed to develop and externally validate a clinical risk score for angiographic no reflow for use following angiography and before PCI., Methods: We developed and externally validated a logistic regression model for prediction of no reflow among adult patients undergoing PCI for acute coronary syndrome using data from the Melbourne Interventional Group PCI registry (2005-2020; development cohort) and the British Cardiovascular Interventional Society PCI registry (2006-2020; external validation cohort)., Results: A total of 30 561 patients (mean age, 64.1 years; 24% women) were included in the Melbourne Interventional Group development cohort and 440 256 patients (mean age, 64.9 years; 27% women) in the British Cardiovascular Interventional Society external validation cohort. The primary outcome (no reflow) occurred in 4.1% (1249 patients) and 9.4% (41 222 patients) of the development and validation cohorts, respectively. From 33 candidate predictor variables, 6 final variables were selected by an adaptive least absolute shrinkage and selection operator regression model for inclusion (cardiogenic shock, ST-segment-elevation myocardial infarction with symptom onset >195 minutes pre-PCI, estimated stent length ≥20 mm, vessel diameter <2.5 mm, pre-PCI Thrombolysis in Myocardial Infarction flow <3, and lesion location). Model discrimination was very good (development C statistic, 0.808; validation C statistic, 0.741) with excellent calibration. Patients with a score of ≥8 points had a 22% and 27% risk of no reflow in the development and validation cohorts, respectively., Conclusions: The no-reflow prediction in acute coronary syndrome risk score is a simple count-based scoring system based on 6 parameters available before PCI to predict the risk of no reflow. This score could be useful in guiding preventative treatment and future trials., Competing Interests: Disclosures None.

Purpose: This prospective study aimed to investigate estrogen-induced carcinogenesis by assessing the background levels of abasic sites (apurinic/apyrimidinic sites, AP sites) in Taiwanese breast cancer patients following 5 years of postoperative treatment without recurrence (5-year survivors) (n = 70). The study also sought to compare the extent of these DNA lesions with those found in healthy controls and in breast cancer patients prior to treatment., Methods: Abasic sites were measured using an aldehyde reactive probe and quantified as the total number of abasic sites per total nucleotides. Characterization of the abasic sites in subjects recruited for this study was conducted using the abasic site cleavage assay using putrescine or T7 exonuclease (T7 Exo) and/or exonuclease III (Exo III)., Results: The number of abasic sites detected in 5 year survivors (26.7 ± 10.2 per 10 6 total nucleotides, n = 70) was significantly reduced by 46.9% compared to those in breast cancer patients before treatment (50.3 ± 59.2 per 10 6 total nucleotides, P < 0.001), and was similar to the levels observed in healthy controls (23.3 ± 13.5 per 10 6 total nucleotides, P > 0.05). Further investigation into the specific types of abasic sites indicated that the number of abasic sites excisable by putrescine in controls, breast cancer patients, and 5-year survivors were 63.3%, 78.6%, and 67.7%, respectively. These findings suggest the involvement of oxidative stress rather than depurination/depyrimidination of DNA adducts in the formation of abasic sites. Further analyses were performed using exonuclease cleavage assay to characterize the specific types of abasic sites including 5'-cleaved, 3'-cleaved, intact, and residual abasic sites. Results demonstrated that the proportion of residual abasic sites detected in controls, breast cancer patients, and 5-year survivors were estimated to be 32.7%, 48.8%, and 34.0%, respectively., Conclusion: Overall, these findings suggest clear evidence of treatment-related effects on the reduction of levels of abasic sites as well as on the profile of abasic sites in 5 year survivors., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors alone are responsible for the content and writing of this article.

The malevolent application of neuroscience is an emerging threat to the U.S. military. At present, U.S. military medical personnel are not capable of adequately diagnosing or treating the injuries and illnesses that may result from exposure to potential neuroweapons. This fact was illustrated in 2016 when U.S. diplomats serving in Havana, Cuba reported hearing strange noises accompanied by a constellation of unexplained health effects. Similar incidents have been reported in China and Russia. Although various hypotheses have been put forward to explain these symptoms, none of them have been verified. The reported symptoms were analogous to the physiological responses that have been produced in the laboratory by exposing volunteers to pulsed microwave energy. However, these incidents of undetermined origin demonstrate that widespread neurological illness can be disruptive to U.S. government operations and that it is currently not possible to identify the cause, determine the correct treatment, or ascribe attribution to potential neuroweapon use in an overseas setting. Since it is likely that Special Operations medical personnel will be among the first to respond to neuroweapon attacks in the deployed environment, it is essential that they be made aware of this emerging threat and that efforts be made to incorporate potential directed energy neuroweapons and other neuroweapon configurations into future Chemical, Biological, Radiological, Nuclear, and high yield Explosives (CBRN-E) training modules. The intention of this article is to introduce the concept of the neuroweapon to military medical personnel and to provide a brief review of the relevant literature., (2023.)

Background: Left ventricular (LV) dysfunction and ischaemic heart disease (IHD) are common among women. However, women tend to present later and are less likely to receive guideline-directed medical therapy (GDMT) compared with men., Methods: We analysed prospectively collected data (2005-2018) from a multicentre registry on GDMT 30 days after percutaneous coronary intervention in 13,015 patients with LV ejection fraction <50%. Guideline-directed medical therapy was defined as beta blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker±mineralocorticoid receptor antagonist. Long-term mortality was determined by linkage with the Australian National Death Index., Results: Women represented 20% (2,634) of the total cohort. Mean age was 65±12 years. Women were on average >5 years, with higher body mass index and higher rates of hypertension, diabetes, renal dysfunction, prior stroke, and rheumatoid arthritis. Guideline-directed medical therapy was similar between sexes (73% vs 72%; p=0.58), although women were less likely to be on an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (80% vs 82%; p=0.02). Women were less likely to be on statin therapy (p<0.001) or a second antiplatelet agent (p=0.007). Women had higher unadjusted long-term mortality (25% vs 19%; p<0.001); however, there were no differences in long-term mortality between sexes on adjusted analysis (hazard ratio 0.99; 95% confidence interval 0.87-1.14; p=0.94)., Conclusions: Rates of GDMT for LV dysfunction were high and similar between sexes; however, women were less likely to be on appropriate IHD secondary prevention. The increased unadjusted long-term mortality in women was attenuated in adjusted analysis, which highlights the need for optimisation of baseline risk to improve long-term outcomes of women with IHD and comorbid LV dysfunction., Competing Interests: Competing Interest Statement SJD’s work is supported by a National Health and Medical Research Council of Australia (NHMRC) Grant (number 1111170). CMR’s work is supported by a NHMRC Principal Research Fellowship (reference no. 1136372)., (Copyright © 2023 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

The ovarian follicle is a complex structure that protects and helps in the maturation of the oocyte, and then releases it through the controlled molecular and structural remodeling process of ovulation. The progesterone receptor (PGR) has been shown to be essential in regulating ovulation-related gene expression changes. In this study, we found disrupted expression of the cellular adhesion receptor gene Sema7A in the granulosa cells of PGR -/- mice during ovulation. We subsequently found that expression of Sema7A in preovulatory follicles is promoted by gonadotropins and hypoxia, establishing an asymmetrical pattern with the SEMA7A protein enriched at the apex of large antral follicles. Sema7A expression was downregulated through a PGR-dependent mechanism in the periovulatory period, the abundance of SEMA7A protein was reduced, and the asymmetric pattern became more homogeneous after an ovulatory stimulus. Receptors for Sema7A can either repel or promote intercellular adhesion. During ovulation, striking inverse regulation of repulsive Plxnc1 and adhesive Itga5/Itgb1 receptors likely contributes to dramatic tissue remodeling. The adhesive receptor Itga5 was significantly increased in periovulatory granulosa cells and cumulus-oocyte complexes (COCs), and functional assays showed that periovulatory granulosa cells and COCs acquire increased adhesive phenotypes, while Sema7A repels granulosa cell contact. These findings suggest that the regulation of Sema7A and its associated receptors, along with the modulation of integrin α5, may be critical in establishing the multilaminar ovarian follicle structure and facilitating the remodeling and apical release of the cumulus-oocyte complex during ovulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Emery, Dunning, Dinh, Akison, Robker and Russell.)

Using an extended full-cycle carbon model from the Faustmann framework, which allows for management strategies of several uses concurrently implemented in the same area of forest, this paper investigates the selection of management objectives that are beneficial and optimal for forest plantations in Vietnam. Three scenarios are considered: Scenario 1 investigates the management objective of maximizing the land economic value (LEV) of timber as a single production. Scenario 2 investigates the joint production of timber and bioenergy sources. Scenario 3 analyzes the joint production of timber, bioenergy production, and carbon sequestration. The findings reveal that if growers pursue a timber management objective (Scenario 1), the farming business only provides considerable benefits under the government-subsidized credit scheme of 8.4%. For a higher non-subsidized interest rate of 15.24% of commercial banks, such gains reduce substantially and become negative value under the mean interest rate of 19.08% of private credit sources. Altering the management objective to a joint production of timber and raw bioenergy production (Scenario 2) will boost the LEV by a moderate level, but at the expense of timber production and thus carbon stock. However, the reduction tendency of timber and carbon balance is not substantial due mainly to the relatively small proportion of bioenergy production compared to timber production; therefore, decision-making frameworks targeting carbon uptake may be capable of incorporating such levels of confliction. Further internalizing the carbon value of the forest into management objectives generally leads to a longer rotation length, thus improving both carbon sequestration and income gains. Shifting the current timber-dominant management objective to a joint production of timber and bioenergy sources, or, alternatively, a joint production of timber, bioenergy production, and carbon sequestration when the carbon market is emerging, is a good alternative strategy for forest management in Vietnam., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: The Korean War (1950-1953) consisted of two phases. The first was a rapid mobile phase, and the second was a slow and stationary phase. During the stationary phase, approximately 3,000 UN troops became infected with a then unknown agent. The resulting illness began with flu-like symptoms and often progressed to a severe hemorrhagic fever leading to kidney failure and death. However, the cause was not to be identified until well over 20 years following the conclusion of the war when Dr. Ho Wang Lee succeeded in isolating Hantavirus from field rodents. The U.S. Military experience with Hantavirus during the Korean War is a case study of the potential impact of war-related environmental change on disease transmission. The lessons learned from this experience should inform future military medical planning and serve as a reminder of the impact that an unknown agent can have on military operations., Materials and Methods: A literature review of all available records with respect to the U.S. Military experience with Hantavirus was conducted. PubMed was the primary search engine used for this review. However, primary literature and historical accounts were also evaluated. All records were examined for environmental, epidemiological, and public health data regarding hemorrhagic fever outbreaks among U.S. forces during the Korean War. The quantitative and qualitative data from these sources were analyzed and evaluated within the context of military medical planning and force health protection to derive lessons learned that should be applied to the management and mitigation of viral disease in future wars., Results: Widespread deforestation resulting from war-related efforts most likely played a significant role in the outbreaks of Hantavirus among UN forces during the war. A lack of cultural literacy and an overreliance on erroneous assumptions most likely delayed the identification of the true causative agent. It is conceivable that these delays led to an increased casualty rate and that they had a negative impact on military operations during the war., Conclusions: A basic understanding of the ecological mechanisms that maintain species diversity in the local environment coupled with an appreciation for the impact of environmental change on this diversity is of paramount importance for the prevention and mitigation of viral disease outbreaks in the deployed setting. Military medical planners should become familiar with the medical literature of the region in which they will be operating as this literature often describes the agents that will most likely be encountered by U.S. forces., (© The Association of Military Surgeons of the United States 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Progesterone receptor (PGR) plays diverse roles in reproductive tissues and thus coordinates mammalian fertility. In the ovary, rapid acute induction of PGR is the key determinant of ovulation through transcriptional control of a unique set of genes that culminates in follicle rupture. However, the molecular mechanisms for this specialized PGR function in ovulation is poorly understood. We have assembled a detailed genomic profile of PGR action through combined ATAC-seq, RNA-seq and ChIP-seq analysis in wildtype and isoform-specific PGR null mice. We demonstrate that stimulating ovulation rapidly reprograms chromatin accessibility in two-thirds of sites, correlating with altered gene expression. An ovary-specific PGR action involving interaction with RUNX transcription factors was observed with 70% of PGR-bound regions also bound by RUNX1. These transcriptional complexes direct PGR binding to proximal promoter regions. Additionally, direct PGR binding to the canonical NR3C motif enable chromatin accessibility. Together these PGR actions mediate induction of essential ovulatory genes. Our findings highlight a novel PGR transcriptional mechanism specific to ovulation, providing new targets for infertility treatments or new contraceptives that block ovulation., (Published by Oxford University Press on behalf of Nucleic Acids Research 2023.)

Objectives: We sought to establish the minimum level of clinical benefit attributable to the Victorian Cardiac Outcomes Registry (VCOR) for the registry to be cost-effective., Design: A modelled cost-effectiveness study of VCOR was conducted from the Australian healthcare system and societal perspectives., Setting: Observed deaths and costs attributed to coronary heart disease (CHD) over a 5-year period (2014-2018) were compared with deaths and costs arising from a hypothetical situation which assumed that VCOR did not exist. Data from the Australian Bureau of Statistics and published sources were used to construct a decision analytic life table model to simulate the follow-up of Victorians aged ≥25 years for 5 years, or until death. The assumed contribution of VCOR to the proportional change in CHD mortality trend observed over the study period was varied to quantify the minimum level of clinical benefits required for the registry to be cost-effective. The marginal costs of VCOR operation and years of life saved (YoLS) were estimated., Primary Outcome Measures: The return on investment (ROI) ratio and the incremental cost-effectiveness ratio (ICER)., Results: The minimum proportional change in CHD mortality attributed to VCOR required for the registry to be considered cost-effective was 0.125%. Assuming this clinical benefit, a net return of $A4.30 for every dollar invested in VCOR was estimated (ROI ratio over 5 years: 4.3 (95% CI 3.6 to 5.0)). The ICER estimated for VCOR was $A49 616 (95% CI $A42 228 to $A59 608) per YoLS. Sensitivity analyses found that the model was sensitive to the time horizon assumed and the extent of registry contribution to CHD mortality trends., Conclusions: VCOR is likely cost-effective and represents a sound investment for the Victorian healthcare system. Our evaluation highlights the value of clinical quality registries in Australia., Competing Interests: Competing interests: PL is supported by an Australian Government Research Training Program (RTP) scholarship. EZ has received grants from Amgen, AstraZeneca, Pfizer, Shire and Zoll Medical, outside the submitted work. DL has received honoraria or study grants from AbbVie, Amgen, Astellas, AstraZeneca, Bohringer Ingelheim, Bristol Myers Squibb, Novartis, Pfizer, Sanofi, Shire and Zoll Medical, outside the submitted work. DS is supported by the National Heart Foundation Fellowship and Viertel Foundation Award. CMR is supported by a National Health and Medical Research Council Principal Research Fellowship (GNT1136372). All other authors have no conflicts of interest to disclose., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The healthy skeletal muscle extracellular matrix (ECM) has several functions including providing structural integrity to myofibers, enabling lateral force transmission, and contributing to overall passive mechanical properties. In diseases such as Duchenne Muscular dystrophy, there is accumulation of ECM materials, primarily collagen, which results in fibrosis. Previous studies have shown that fibrotic muscle is often stiffer than healthy muscle, in part due to the increased number and altered architecture of collagen fibers within the ECM. This would imply that the fibrotic matrix is stiffer than the healthy matrix. However, while previous studies have attempted to quantify the extracellular contribution to passive stiffness in muscle, the outcomes are dependent on the type of method used. Thus, the goals of this study were to compare the stiffness of healthy and fibrotic muscle ECM and to demonstrate the efficacy of two methods for quantifying extracellular-based stiffness in muscle, namely decellularization and collagenase digestion. These methods have been demonstrated to remove the muscle fibers or ablate collagen fiber integrity, respectively, while maintaining the contents of the extracellular matrix. Using these methods in conjunction with mechanical testing on wildtype and D2. mdx mice, we found that a majority of passive stiffness in the diaphragm is dependent on the ECM, and the D2. mdx diaphragm ECM is resistant to digestion by bacterial collagenase. We propose that this resistance is due to the increased collagen cross-links and collagen packing density in the ECM of the D2. mdx diaphragm. Taken altogether, while we did not find increased stiffness of the fibrotic ECM, we did observe that the D2. mdx diaphragm conveyed resistance against collagenase digestion. These findings demonstrate how different methods for measuring ECM-based stiffness each have their own limitations and can produce different results., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lucas Smith reports financial support was provided by National Institute of Arthritis and Musculoskeletal and Skin Diseases., (© 2023 The Author(s).)

Although curcumin in the form of nanoparticles has been demonstrated as a potential anti-tumor compound, the impact of curcumin and nanocurcumin in vitro on normal cells and in vivo in animal models is largely unknown. This study evaluated the toxicity of curcumin-loaded micelles in vitro and in vivo on several tumor cell lines, primary stromal cells, and zebrafish embryos. Breast tumor cell line (MCF7) and stromal cells (human umbilical cord vein endothelial cells, human fibroblasts, and human umbilical cord-derived mesenchymal stem cells) were used in this study. A zebrafish embryotoxicity (FET) assay was conducted following the Organisation for Economic Co-operation and Development (OECD) Test 236. Compared to free curcumin, curcumin PM showed higher cytotoxicity to MCF7 cells in both monolayer culture and multicellular tumor spheroids. The curcumin-loaded micelles efficiently penetrated the MCF7 spheroids and induced apoptosis. The nanocurcumin reduced the viability and disturbed the function of stromal cells by suppressing cell migration and tube formation. The micelles demonstrated toxicity to the development of zebrafish embryos. Curcumin-loaded micelles demonstrated toxicity to both tumor and normal primary stromal cells and zebrafish embryos, indicating that the use of nanocurcumin in cancer treatment should be carefully investigated and controlled.

Peri-procedural stroke (PPS) is an important complication in patients who underwent percutaneous coronary intervention (PCI). The extent to which PPS impacts mortality and outcomes remains to be defined. Consecutive patients who underwent PCI enrolled in the Victorian Cardiac Outcomes Registry (2014 to 2018) were categorized into PPS and no PPS groups. The primary outcome was 30-day major adverse cardiovascular events (MACEs) (composite of mortality, myocardial infarction, stent thrombosis, and unplanned revascularization). Of 50,300 patients, PPS occurred in 0.26% patients (n = 133) (71% ischemic, and 29% hemorrhagic etiology). Patients who developed PPS were older (69 vs 66 years) compared with patients with no PPS, and more likely to have pre-existing heart failure (59% vs 29%), chronic kidney disease (33% vs 20%), and previous cerebrovascular disease (13% vs 3.6%), p &lt;0.01. Among those with PPS, there was a higher frequency of presentation with ST-elevation myocardial infarction (49% vs 18%) and out-of-hospital cardiac arrest (14% vs 2.2%), PCI by way of femoral access (59% vs 46%), and adjunctive thrombus aspiration (12% vs 3.6%), all p = &lt;0.001. PPS was associated with incident 30-day MACE (odds ratio [OR] 2.97, 95% confidence intervals [CIs] 1.86 to 4.74, p &lt;0.001) after multivariable adjustment. Utilizing inverse probability of treatment weighting analysis, PPS remained predictive of 30-day MACE (OR 1.91, 95% CI 1.31 to 2.80, p = 0.001) driven by higher 30-day mortality (OR 2.0, 95% CI 1.35 to 2.96, p = 0.001). In conclusion, in this large, multi-center registry, the incidence of PPS was low; however, its clinical sequelae were significant, with a twofold increased risk of 30-day MACE and all-cause death., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Renal impairment post-percutaneous coronary intervention (post-PCI) is a well-described adverse effect following the administration of contrast media. Within a large cohort of registry patients, we aimed to explore the incidence, predictors and clinical outcomes of renal impairment post-PCI., Methods: The Victorian Cardiac Outcomes Registry is an Australian state-based clinical quality registry focusing on collecting data from all PCI capable centres. Data from 36 970 consecutive PCI cases performed between 2014 and 2018 were analysed. Patients were separated into three groups based on post-procedure creatinine levels (new renal impairment (NRI), defined as an absolute rise in serum creatinine>44.2 µmol/L or>25% of baseline creatinine; new renal impairment requiring dialysis (NDR), defined as worsening renal failure that necessitated a new requirement for renal dialysis; no NRI). Multivariate logistic regression analysis was performed to investigate the impact of NRI and NDR on clinical outcomes., Results: 3.1% (n=1134) of patients developed NRI, with an additional 0.6% (n=225) requiring dialysis. 96.3% (n=35 611) of patients did not develop NRI. Those who developed renal impairment were more comorbid, with higher rates of diabetes (22% vs 38% vs 38%, p<0.001), peripheral vascular disease (3.4% vs 8.2% vs 11%, p<0.001), chronic kidney disease (19% vs 49.7% vs 54.2%) and severe left ventricular dysfunction (5% vs 22% vs 40%, p<0.001). Multivariable analysis found that when compared with the no NRI group, those in the combined NRI/NDR group were at a greater risk of 30-day mortality (OR 4.77; 95% CI 3.89 to 5.86, p<0.001) and 30-day major adverse cardiac events (OR 3.72; 95% CI 3.15 to 4.39, p<0.001)., Conclusions: NRI post-PCI remains a common occurrence, especially among comorbid patients, and is associated with a significantly increased morbidity and mortality risk., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Patient factors, such as sex and body mass index (BMI), are known to influence patient radiation exposure. Body surface area (BSA) and its association with patient radiation exposure has not been well studied., Methods and Results: We analysed height, weight, BMI and BSA in consecutive patients undergoing cardiac catheterisation and percutaneous coronary intervention (PCI) at a high-volume Australian centre between September 2016 and April 2020 to assess their association with dose-area product (DAP, Gycm 2 ). The mean age of the cohort was 64.5 ± 12.3 years with males comprising 68.8% ( n = 8100, 5124 diagnostic cardiac catheterisation cases and 2976 PCI cases). Median male BMI was 28.4 kg/m 2 [IQR 25.2-32.1] versus 28.8 kg/m 2 [24.7-33.7] for females, p = 0.01. Males had higher BSA (2.0 ± 0.2 m 2 ) than females (1.78 ± 0.2 m 2 ), p = 0.001. Each 0.4 m 2 increase in BSA conferred a 1.32x fold change in DAP (95% CI 1.29-1.36, p ≤ 0.001). Each 5 kg/m 2 increase in BMI was linked to a 1.13x DAP fold change (1.12-1.14, p ≤ 0.001). Male sex conferred a 1.23x DAP fold change (1.20-1.26, p ≤ 0.001). Multivariable modelling with BMI or BSA explained 14% of DAP variance (R 2 0.67 vs. 0.53 for both, p ≤ 0.001)., Conclusions: BSA is an important anthropometric measure between the sexes and a key predictor of radiation dose and radiation exposure beyond sex, BMI, and weight.

Against the backdrop of a global pandemic, the Society for Reproductive Biology (SRB) 2021 meeting reunited the Australian and New Zealand reproductive research community for the first time since 2019 and was the first virtual SRB meeting. Despite the recent global research disruptions, the conference revealed significant advancements in reproductive research, the importance of which span human health, agriculture, and conservation. A core theme was novel technologies, including the use of medical microrobots for therapeutic and sperm delivery, diagnostic hyperspectral imaging, and hydrogel condoms with potential beyond contraception. The importance of challenging the contraceptive status quo was further highlighted with innovations in gene therapies, non-hormonal female contraceptives, epigenetic semen analysis, and in applying evolutionary theory to suppress pest population reproduction. How best to support pregnancies, particularly in the context of global trends of increasing maternal age, was also discussed, with several promising therapies for improved outcomes in assisted reproductive technology, pre-eclampsia, and pre-term birth prevention. The unique insights gained via non-model species was another key focus and presented research emphasised the importance of studying diverse systems to understand fundamental aspects of reproductive biology and evolution. Finally, the meeting highlighted how to effectively translate reproductive research into policy and industry practice.

Purpose: During the COVID-19 pandemic, widespread public health measures were implemented to control community transmission. The association between these measures and health-related quality of life (HRQOL) among patients following percutaneous coronary intervention has not been studied., Methods: We included consecutive patients undergoing percutaneous coronary intervention (PCI) in the state-wide Victorian Cardiac Outcomes Registry between 1/3/2020 and 30/9/2020 (COVID-19 period; n = 5024), with a historical control group from the identical period one year prior (control period; n = 5041). HRQOL assessment was performed via telephone follow-up 30 days following PCI using the 3-level EQ-5D questionnaire and Australian-specific index values., Results: Baseline characteristics were similar between groups, but during the COVID-19 period indication for PCI was more common for acute coronary syndromes. No patients undergoing PCI were infected with COVID-19 at the time of their procedure. EQ-5D visual analogue score (VAS), index score, and individual components were higher at 30 days following PCI during the COVID-19 period (all P < 0.01). In multivariable analysis, the COVID-19 period was independently associated with higher VAS and index scores. No differences were observed between regions or stage of restrictions in categorical analysis. Similarly, in subgroup analysis, no significant interactions were observed., Conclusion: Measures of HRQOL following PCI were higher during the COVID-19 pandemic compared to the previous year. These data suggest that challenging community circumstances may not always be associated with poor patient quality of life., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

We investigated changes in some laboratory indices and the liver histology of chronic hepatitis patients who were exposed to dioxin. In 2014, we collected liver biopsy samples for histopathological examination from 33 chronic hepatitis patients living around the Da Nang Airbase, which is a dioxin-contaminated area due to the herbicide spraying in Vietnam. Dioxin exposure was measured by its levels in the blood. METAVIR classification was used to clarify the liver fibrosis stage. Laboratory tests included ten biochemical and six hematological indices that were measured in the blood. A regression linear model and binary logistic regression were used for data analysis. The observed alterations in the liver at the histological level mainly comprised hydropic degenerative hepatocytes, lymphocytes and polynuclear leukocytes surrounding the liver cells and granular and lipoic degeneration. In addition, increased TCDD levels were associated with increasing aminotransferase (AST), alanine aminotransferase, protein and total bilirubin levels and liver fibrosis stage. Similarly, increased TEQ-PCDD/Fs levels were associated with higher levels of AST and protein and liver fibrosis stage. In conclusion, dioxin exposure altered the liver histology and increased some biochemical marker indices and the liver fibrosis stage of chronic hepatitis patients living in dioxin-contaminated areas in Da Nang, Vietnam.

Aims: We sought to investigate if sex disparity exists for secondary prevention pharmacotherapy following acute coronary syndrome (ACS) and impact on long-term clinical outcomes., Methods and Results: We analysed data on medical management 30-day post-percutaneous coronary intervention (PCI) for ACS in 20 976 patients within the multicentre Melbourne Interventional Group registry (2005-2017). Optimal medical therapy (OMT) was defined as five guideline-recommended medications, near-optimal medical therapy (NMT) as four medications, sub-optimal medical therapy (SMT) as ≤3 medications. Overall, 65% of patients received OMT, 27% NMT and 8% SMT. Mean age was 64 ± 12 years; 24% (4931) were female. Women were older (68 ± 12 vs. 62 ± 12 years) and had more comorbidities. Women were less likely to receive OMT (61% vs. 66%) and more likely to receive SMT (10% vs. 8%) compared to men, P < 0.001. On long-term follow-up (median 5 years, interquartile range 2-8 years), women had higher unadjusted mortality (20% vs. 13%, P < 0.001). However, after adjusting for medical therapy and baseline risk, women had lower long-term mortality [hazard ratio (HR) 0.88, 95% confidence interval (CI) 0.79-0.98; P = 0.02]. NMT (HR 1.17, 95% CI 1.05-1.31; P = 0.004) and SMT (HR 1.79, 95% CI 1.55-2.07; P < 0.001) were found to be independent predictors of long-term mortality., Conclusion: Women are less likely to be prescribed optimal secondary prevention medications following PCI for ACS. Lower adjusted long-term mortality amongst women suggests that as well as baseline differences between gender, optimization of secondary prevention medical therapy amongst women can lead to improved outcomes. This highlights the need to focus on minimizing the gap in secondary prevention pharmacotherapy between sexes following ACS., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Progesterone receptor (PGR) activity is obligatory for mammalian ovulation; however, there is no established direct functional pathway explaining how progesterone receptor completely and specifically regulates oocyte release. This study examined the overarching cell- and isoform-specific effects of the PGR within each cellular compartment of the ovary, using mice null for the PGR (PRKO), as well as isoform-specific null mice. The PGR was expressed in ovarian granulosa and stromal cells and although PRKO ovaries showed no visible histological changes in preovulatory ovarian morphology, follicle rupture did not occur. Reciprocal ovarian transplant experiments established the necessity of ovarian PGR expression for ovulation. Cumulus-oocyte complexes of PRKO mice exhibited normal morphology but showed some altered gene expression. The examination of mitochondrial activity showed subtle differences in PRKO oocytes but no differences in granulosa cell respiration, glycolysis or β-oxidation. Concurrently, RNA-seq identified novel functional pathways through which the PGR may regulate ovulation. PGR-A was the predominant transcriptionally active isoform in granulosa cells and 154 key PGR-dependent genes were identified, including a secondary network of transcription factors. In addition, the PGR regulated unique gene networks in the ovarian stroma. Collectively, we establish the effector pathways activated by the PGR across the ovarian cell types and conclude that PGR coordinates gene expression in the cumulus, granulosa and stromal cells at ovulation. Identifying these networks linking the PGR to ovulation provides novel targets for fertility therapeutics and nonhormonal contraceptive development.

Background Atmospheric changes in pollen concentration may affect human health by triggering various allergic processes. We sought to assess if changes in pollen concentrations were associated with different acute coronary syndrome (ACS) subtype presentations and short-term clinical outcomes. Methods and Results We analyzed data in consecutive patients presenting with ACS (unstable angina, non-ST-segment-elevation myocardial infarction, and ST-segment-elevation myocardial infarction) treated with percutaneous coronary intervention between January 2014 and December 2017 and enrolled in the VCOR (Victorian Cardiac Outcomes Registry). Baseline characteristics were compared among patients exposed to different grass and total pollen concentrations. The primary outcome was occurrence of ACS subtypes and 30-day major adverse cardiac and cerebrovascular events (composite of mortality, myocardial infarction, stent thrombosis, target vessel revascularization, or stroke). Of 15 379 patients, 7122 (46.3%) presented with ST-segment-elevation myocardial infarction, 6781 (44.1%) with non-ST-segment-elevation myocardial infarction, and 1476 (9.6%) with unstable angina. The mean age was 62.5 years, with men comprising 76% of patients. No association was observed between daily or seasonal grass and total pollen concentrations with the frequency of ACS subtype presentation. However, grass and total pollen concentrations in the preceding days (2-day average for grass pollen and 7-day average for total pollen) correlated with in-hospital mortality (odds ratio [OR], 2.17 [95% CI, 1.12-4.21]; P =0.021 and OR, 2.78 [95% CI, 1.00-7.74]; P =0.05), respectively, with a trend of 2-day grass pollen for 30-day major adverse cardiac and cerebrovascular events (OR, 1.50 [95% CI, 0.97-2.32]; P =0.066). Conclusions Increased pollen concentrations were not associated with differential ACS subtype presentation but were significantly related to in-hospital mortality following percutaneous coronary intervention, underscoring a potential biologic link between pollen exposure and clinical outcomes.

Background: Acute decompensated heart failure (ADHF) is the most common cause of hospital admission in patients over 65, with poorer outcomes demonstrated in rural versus metropolitan areas. The aim of this study was to compare the in-hospital and post-discharge management of ADHF patients admitted to rural versus metropolitan hospitals in Victoria., Methods: Data from the Victorian Cardiac Outcomes Registry, Heart Failure (VCOR-HF) project was used. This was a prospective, observational, non-randomised study of consecutive patients admitted to participating hospitals in Victoria, Australia, with ADHF as their primary diagnosis over four 30-day periods during consecutive years. All patients were followed up for 30 days post discharge., Results: 1,357 patients (1,260 metropolitan, 97 rural) were admitted to study hospitals with ADHF during the study periods. Cohorts were similar in age (average 76.87±13.12 yrs) and percentage of male gender (56.4% overall). Metropolitan patients were more likely to have diabetes (44.4% vs 34.0%, p=0.046), kidney disease (65.8% vs 37.1%, p<0.01) and anaemia (31.9% vs 19.6%, p=0.01). There was no significant difference in length of stay between metropolitan and rural patients (7.49 vs 6.37 days, p=0.12). There was no significant difference between metropolitan and rural patients in 30-day rehospitalisations (19.1% vs 11.6%, p=0.07, respectively) and all-cause 30-day mortality (8.2% vs 4.1%, p=0.15, respectively). Metropolitan patients were significantly more likely to have seen their general practitioner (GP) (68.1% vs 53.2%, p<0.01) or attend an outpatient clinic (35.9% vs 10.6%, p<0.01) by 30 days. There was no significant difference in number of days to follow-up of any kind between groups. Referrals to a heart failure home visiting program remained low overall (19.9%)., Conclusion: There was no significant difference in 30-day rehospitalisations or mortality between patients admitted to rural versus metropolitan hospitals. Geographical discrepancies were noted in follow-up by 30 days, with significantly more metropolitan patients having seen a doctor by 30 days post-discharge. Overall follow-up rates remain suboptimal., (Copyright © 2021 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Objectives: Patients with ST-elevation myocardial infarction (STEMI) that occur while already in hospital ('in-hospital STEMI') face high mortality. However, data about this patient population are scarce. We sought to investigate differences in reperfusion and outcomes of in-hospital versus out-of-hospital STEMI., Design, Setting and Participants: Consecutive patients with STEMI all treated with percutaneous coronary intervention (PCI) across 30 centres were prospectively recruited into the Victorian Cardiac Outcomes Registry (2013-2018)., Primary and Secondary Outcomes: Patients with in-hospital STEMI were compared with patients with out-of-hospital STEMI with a primary endpoint of 30-day major adverse cardiovascular events (MACE). Secondary endpoints included ischaemic times, all-cause mortality and major bleeding., Results: Of 7493 patients with PCI-treated STEMI, 494 (6.6%) occurred in-hospital. Patients with in-hospital STEMI were older (67.1 vs 62.4 years, p<0.001), more often women (32% vs 19.9%, p<0.001), with more comorbidities. Patients with in-hospital STEMI had higher 30-day MACE (20.4% vs 9.8%, p<0.001), mortality (12.1% vs 6.9%, p<0.001) and major bleeding (4.9% vs 2.3%, p<0.001), than patients with out-of-hospital STEMI. According to guideline criteria, patients with in-hospital STEMI achieved symptom-to-device times of ≤70 min and ≤90 min in 29% and 47%, respectively. Patients with out-of-hospital STEMI achieved door-to-device times of ≤90 min in 71%. Occurrence of STEMI while in hospital independently predicted higher MACE (adjusted OR 1.77, 95% CI 1.33 to 2.36, p<0.001) and 12-month mortality (adjusted OR 1.49, 95% CI 1.08 to 2.07, p<0.001)., Conclusions: Patients with in-hospital STEMI experience delays to reperfusion with significantly higher MACE and mortality, compared with patients with out-of-hospital STEMI, after adjustment for confounders. Focused strategies are needed to improve recognition and outcomes in this high-risk and understudied population., Competing Interests: Competing interests: JS is supported by a Monash University scholarship. RD receives teaching and travel grants from Abbott, Medtronic and Boehringer. He serves on the advisory board of Astra Zeneca. SJD is proctor for Medtronic and his work is supported by a grant (1111170) from the National Health and Medical Research Council of Australia. SZ has obtained research funding from Abbott Vascular, Biotronik Australia and Medtronic Australia and speaking honoraria from AstraZeneca. All other authors have no conflicts of interest., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aim: Low-grade gliomas (LGG) are heterogenous tumours, causing variable survivals in patients. Identifying molecular markers for a more accurate prognosis is, therefore, important. Since death receptor 6 (DR6) is up-regulated in gliomas and shows an aberrant signalling network, we tested its suitability as a prognostic marker., Materials and Methods: DR6 was investigated in patient samples via PCR and western blot. Clinical data were analysed and compared to The Cancer Genome Atlas (TCGA) 'brain lower grade glioma' dataset., Results: DR6 was found to be enhanced in LGG and its expression increased in recurrent LGG. The receptor showed a protective effect in primary LGG with a significantly elongated progression-free survival that was confirmed in the TCGA study. This effect was reversed in relapsed LGG in which cases with high DR6 expression reveal a shorter overall survival., Conclusion: DR6 is an interesting candidate for further studies regarding its effect as a prognostic marker, playing an opposing role in primary and relapsed LGG., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)