Spatial proteomics of human diabetic kidney disease, from health to class III.

AIMS/HYPOTHESIS: Diabetic kidney disease (DKD) is the leading cause of chronic and end-stage kidney disease in the USA and worldwide. Animal models have taught us much about DKD mechanisms, but translation of this knowledge into treatments for human disease has been slowed by the lag in our molecular understanding of human DKD. METHODS: Using our Spatial TissuE Proteomics (STEP) pipeline (comprising curated human kidney tissues, multiplexed immunofluorescence and powerful analysis tools), we imaged and analysed the expression of 21 proteins in 23 tissue sections from individuals with diabetes and healthy kidneys (n=5), compared to those with DKDIIA, IIA-B and IIB (n=2 each) and DKDIII (n=1). RESULTS: These analyses revealed the existence of 11 cellular clusters (kidney compartments/cell types): podocytes, glomerular endothelial cells, proximal tubules, distal nephron, peritubular capillaries, blood vessels (endothelial cells and vascular smooth muscle cells), macrophages, myeloid cells, other CD45+ inflammatory cells, basement membrane and the interstitium. DKD progression was associated with co-localised increases in inflammatory cells and collagen IV deposition, with concomitant loss of native proteins of each nephron segment. Cell-type frequency and neighbourhood analyses highlighted a significant increase in inflammatory cells and their adjacency to tubular and αSMA+ (α-smooth muscle actin-positive) cells in DKD. Finally, DKD progression showed marked regional variability within single tissue sections, as well as inter-individual variability within each DKD class. CONCLUSIONS/INTERPRETATION: Using the STEP pipeline, we found alterations in protein expression, cellular phenotypic composition and microenvironment structure with DKD progression, demonstrating the power of this pipeline to reveal the pathophysiology of human DKD.

Advocating for language equity: a community-public health partnership.

In the United States, 21.5% of individuals aged 5 or older speak a language other than English at home and 8.2% have Limited English Proficiency (LEP). LEP individuals experience healthcare disparities, including lower access to healthcare services, poorer health outcomes, and higher levels of uninsurance. The COVID-19 pandemic highlighted and exacerbated these health disparities and unmet healthcare needs. In Alameda County (CA), where 46% of foreign-born residents speak a language other than English at home, community-based organizations have been crucial in providing translated materials and one-on-one support to ensure LEP residents receive critical COVID-19 updates and services. Refugee and Immigrant Collaborative for Empowerment (RICE) is a multilingual coalition of seven Alameda County community-based organizations led by the Korean Community Center of the East Bay (KCCEB). During the COVID-19 pandemic, RICE expanded its public health role to fill service and information gaps, advocate on behalf of LEP groups, and build a linguistically and culturally responsive public health safety network. This community case study describes a three-part advocacy-focused intervention that RICE undertook from September 2021 to October 2022. It included (1) a community needs survey, (2) a landscape assessment of the Alameda County Health Department's (ACPHD) communication materials and online platforms, and (3) relationship building with the ACPHD. The community survey revealed differences across LEP subgroups and highlighted the importance of gathering data disaggregated by language preference. The landscape assessment allowed RICE to understand the ACPHD's decision-making process and develop data-informed advocacy requests on behalf of LEP communities. Effective communication and coordination between RICE and the ACPHD shortened the feedback loop between public health authorities and LEP communities and laid the groundwork for the RICE organizations to be part of the ACPHD's future decision making. Data disaggregation, language equity-based advocacy, and cross-sector collaboration were critical ingredients in RICE's intervention. RICE's partnership and relationship of mutual accountability with the ACPHD may provide a useful model for other community-based organizations and public health departments seeking to form similar partnerships.

The Western and Chinese exercise training for blood pressure reduction among hypertensive patients: An overview of systematic reviews.

Hypertension remains the world's leading cause of premature death. Interventions such as exercise, diet modification, and pharmacological therapy remain the mainstay of hypertension treatment. Numerous systematic reviews and meta-analyses demonstrated the effectiveness of western exercises, such as aerobic exercise and resistance exercise, in reducing blood pressure in hypertensive patients. There is recently emerging evidence of blood pressure reduction with Chinese exercises, such as Tai Chi, Baduanjin, and Qigong. The current overview of systematic reviews aims to evaluate the quality and descriptively summarize the evidence for the effectiveness of western and Chinese exercises for hypertension management. Thirty-nine systematic reviews were included in this overview, with 15 of those being on Chinese exercise. Evidence suggests that exercise training, regardless of Western or Chinese exercise, generally reduced both systolic and diastolic blood pressure. High-intensity intermittent training did not further reduce blood pressure when compared to moderate-intensity continuous training. Conflicting results on the effectiveness of blood pressure reduction when comparing Chinese and Western exercise training were observed. This suggests the comparable effectiveness of Chinese exercise training, in particularly Tai Chi, to general or aerobic exercise training in terms of blood pressure reduction. The Chinese exercise modality and intensity may be more suitable for the middle-aged and elderly population.

3D Imaging for Cleared Tissues and Thicker Samples on Confocal and Light-Sheet Microscopes.

Advances in fluorescence microscopy, specifically the development of confocal and light-sheet microscopes, have enabled researchers to harness tissue clearing techniques to image-stained intact tissue samples in 3D. Using these techniques, tissue structure and biomarker distributions in 3D structures are preserved, thus allowing researchers to gain a wealth of spatial information about their tissue of interest. However, the execution of imaging these larger tissue samples can be challenging. Broadly speaking, tissue clearing techniques unify the refractive indices inside tissue samples, thus enabling deep tissue imaging on a confocal or light-sheet microscope. Here, we provide an overview to tissue clearing and 3D immunohistochemistry staining in general and discuss some difficulties that researchers may encounter when using these techniques. We then focus on imaging CLARITY-processed samples with both confocal and light-sheet microscopes and optimizing the acquisition parameters, before noting potential issues that may come up in imaging.

DIY liquid handling robots for integrated STEM education and life science research.

Automation has played a key role in improving the safety, accuracy, and efficiency of manufacturing and industrial processes and has the potential to greatly increase throughput in the life sciences. However, the lack of accessible entry-point automation hardware in life science research and STEM education hinders its widespread adoption and development for life science applications. Here we investigate the design of a low-cost (~$150) open-source DIY Arduino-controlled liquid handling robot (LHR) featuring plastic laser-cut parts. The robot moves in three axes with 0.5 mm accuracy and reliably dispenses liquid down to 20 µL. The open source, modular design allows for flexibility and easy modification. A block-based programming interface (Snap4Arduino) further extends the accessibility of this robot, encouraging adaptation and use by educators, hobbyists and beginner programmers. This robot was co-designed with teachers, and we detail the teachers' feedback in the context of a qualitative study. We conclude that affordable and accessible LHRs similar to this one could provide a useful educational tool to be deployed in classrooms, and LHR-based curricula may encourage interest in STEM and effectively introduce automation technology to life science enthusiasts.

Drug-drug interactions between direct-acting antivirals and co-medications: a territory-wide cohort study.

BACKGROUND: The increasing number of direct-acting antiviral (DAA) regimens along with limited number of subjects and co-medications involved in clinical trials results in drug-drug interactions (DDIs) with DAAs is to be determined. We aimed to examine the prevalence and degree of DDIs between DAAs and other co-medications in a territory-wide cohort of chronic hepatitis C virus (HCV) patients. METHODS: DDIs were assigned to three risk categories: Category 1-no clinically significant DDI; category 2-potential clinically significant interaction (monitoring and caution required); category 3-contraindicated (should not be co-administered). RESULTS: Of 2981 patients (mean age 59.3 ± 12.3 years; male 60.6%), 810 (48.8%) had genotype 1 and 552 (33.2%) genotype 6 HCV among the 1661 patients with HCV genotype tested; 769 (25.8%) received sofosbuvir/velpatasvir, 510 (17.1%) sofosbuvir/ledipasvir, and 865 (29.0%) glecaprevir/pibrentasvir. More than one-fourth (26.3%) of the patients have polypharmacy (≥ 3 co-medications) in all patients, 27.0% in patients received sofosbuvir/velpatasvir, 25.1% in elbasvir/grazoprevir, and 21.2% in glecaprevir/pibrentasvir. 2037 (68.3%) patient experienced DDI (Category 2: 53.1%; Category 3: 15.2%). The commonest drugs leading to DDIs were calcium channel blockers (31.5%) and proton pump inhibitors (23.0%) in category 2; statins (10.2%), antiplatelet/anticoagulants (3.0%) and antipsychotics (2.9%) in category 3. Changing medication was the most common response from physicians in both category 2 and 3 DDIs. CONCLUSION: The commonest co-medications leading to contraindication during DAA treatment were statins and antipsychotics. Category 2 and 3 DDIs are often managed by appropriate dose adjustments or temporary discontinuation of relevant co-medications. Careful assessment for potential DDI before DAA use is mandatory to avoid potential harmful effects.

Viral Size Modulates Sendai Virus Binding to Cholesterol-Stabilized Receptor Nanoclusters.

Binding to the host membrane is the initial infection step for animal viruses. Sendai virus (SeV), the model respirovirus studied here, utilizes sialic-acid-conjugated glycoproteins and glycolipids as receptors for binding. In a previous report studying single virus binding to supported lipid bilayers (SLBs), we found a puzzling mechanistic difference between the binding of SeV and influenza A virus (strain X31, IAVX31). Both viruses use similar receptors and exhibit similar cooperative binding behavior, but whereas IAVX31 binding was altered by SLB cholesterol concentration, which can stabilize receptor nanoclusters, SeV was not. Here, we propose that differences in viral size distributions can explain this discrepancy; viral size could alter the number of virus-receptor interactions in the contact area and, therefore, the sensitivity to receptor nanoclusters. To test this, we compared the dependence of SeV binding on SLB cholesterol concentration between size-filtered and unfiltered SeV. At high receptor density, the unfiltered virus showed little dependence, but the size-filtered virus exhibited a linear cholesterol dependence, similar to IAVX31. However, at low receptor densities, the unfiltered virus did exhibit a cholesterol dependence, indicating that receptor nanoclusters enhance viral binding only when the number of potential virus-receptor interactions is small enough. We also studied the influence of viral size and receptor nanoclusters on viral mobility following binding. Whereas differences in viral size greatly influenced mobility, the effect of receptor nanoclusters on mobility was small. Together, our results highlight the mechanistic salience of both the distribution of viral sizes and the lateral distribution of receptors in a viral infection.

Tenofovir alafenamide is associated with improved alanine aminotransferase and renal safety compared to tenofovir disoproxil fumarate.

Tenofovir alafenamide (TAF) is a novel prodrug of tenofovir for the treatment of chronic hepatitis B (CHB) infection. We aimed to evaluate the impact of switching to TAF on alanine aminotransferase (ALT) normalization and renal safety. We also described the indications of switching to TAF. Consecutive adult CHB patients switched from tenofovir disoproxil fumarate (TDF) dominant therapy to TAF for more than 12 months were identified retrospectively. A subgroup of patients newly switched to TAF was prospectively invited to perform transient elastography examination and dual-energy X-ray absorptiometry. The time of switching to TAF was defined as baseline. Among 393 patients in the retrospective cohort, the median ALT at month 12 was significantly lower (21.0 [16.0-29.9] U/L vs. 25.0 [19.0-34.0] U/L; p < 0.001) and ALT normalization rate was higher (89.9% vs. 83.7%; p = 0.037) than those at baseline. Estimated glomerular filtration rate decreased from 12 months before baseline and then increased from baseline to month 12 significantly (69.7 ± 22.0 ml/min/1.73 m2 vs. 68.5 ± 21.5 ml/min/1.73 m2 vs. 69.2 ± 21.5 ml/min/1.73 m2 , p = 0.002 (-12 m vs. baseline), p = 0.004 (baseline vs. 12 m)). In the prospective cohort, 103 patients switched to TAF because of age > 60 years (63.1%), bone diseases (54.4%), and renal alteration (42.7%). TAF is associated with ALT improvement and better renal safety than TDF dominant therapy in CHB patients. Most CHB patients switched to TAF because of advanced age, followed by bone disease and renal alteration.

Single-virus assay reveals membrane determinants and mechanistic features of Sendai virus binding.

Sendai virus (SeV, formally murine respirovirus) is a membrane-enveloped, negative-sense RNA virus in the Paramyxoviridae family and is closely related to human parainfluenza viruses. SeV has long been utilized as a model paramyxovirus and has recently gained attention as a viral vector candidate for both laboratory and clinical applications. To infect host cells, SeV must first bind to sialic acid glycolipid or glycoprotein receptors on the host cell surface via its hemagglutinin-neuraminidase (HN) protein. Receptor binding induces a conformational change in HN, which allosterically triggers the viral fusion (F) protein to catalyze membrane fusion. While it is known that SeV binds to α2,3-linked sialic acid receptors, and there has been some study into the chemical requirements of those receptors, key mechanistic features of SeV binding remain unknown, in part because traditional approaches often convolve binding and fusion. Here, we develop and employ a fluorescence microscopy-based assay to observe SeV binding to supported lipid bilayers (SLBs) at the single-particle level, which easily disentangles binding from fusion. Using this assay, we investigate mechanistic questions of SeV binding. We identify chemical structural features of ganglioside receptors that influence viral binding and demonstrate that binding is cooperative with respect to receptor density. We measure the characteristic decay time of unbinding and provide evidence supporting a "rolling" mechanism of viral mobility following receptor binding. We also study the dependence of binding on target cholesterol concentration. Interestingly, we find that although SeV binding shows striking parallels in cooperative binding with a prior report of Influenza A virus, it does not demonstrate a similar sensitivity to cholesterol concentration and receptor nanocluster formation.

FRET Imaging of Rho GTPase Activity with Red Fluorescent Protein-Based FRET Pairs.

With the development of fluorescent proteins (FPs) and advanced optical microscopy techniques, Förster or fluorescence resonance energy transfer (FRET) has become a powerful tool for real-time noninvasive visualization of a variety of biological processes, including kinase activities, with high spatiotemporal resolution in living cells and organisms. FRET can be detected in appropriately configured microscopes as changes in fluorescence intensity, lifetime, and anisotropy. Here, we describe the preparation of samples expressing FP-based FRET sensors for RhoA kinase, intensity- and lifetime-based FRET imaging, and postimaging data analysis.

Antihypertensive treatments and risks of lung Cancer: a large population-based cohort study in Hong Kong.

BACKGROUND: There is a growing concern that the use of anti-hypertensives may be associated with an increased risk of cancer, but it remains uncertain for the association between anti-hypertensives and lung cancer risk, as well as their interaction with aspirin in chemoprotective effects. METHODS: The goal of this study is to assess the association between anti-hypertensives use and the risk of lung cancer, as well as the chemopreventive impacts from the combination usage of aspirin and anti-hypertensives. A retrospective cohort study was conducted based on all the public hospital electronic medical records in Hong Kong. Patients with prescription records of anti-hypertensives (ACEi/ARB, CCB, ß-blocker,α-blocker) and/or aspirin were included as the exposure groups. Using the Cox proportional hazards model with inverse probability weighting, we estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for lung cancer risk from anti-hypertensives usage or combination usage of aspirin with anti-hypertensives. The likelihood ratio test and interaction model were adopted for exploring the interaction effects with aspirin. RESULTS: A total of 6592 and 84,116 lung cancer cases were identified from the groups of anti-hypertensives users and anti-hypertensives users with aspirin, respectively. The group of non-aspirin patients who received anti-hypertensives showed a significantly lower risk of lung cancer (HR: 0.63, 95% CI: 0.60-0.66), compared to those without anti-hypertensives. When aspirin and α-blocker were used simultaneously, it could lower the risk of lung cancer significantly (HR: 0.53, 95% CI: 0.34-0.84). Moreover, the lower risk of lung cancer persisted with a longer follow-up period of anti-hypertensives usage. Combination usage with aspirin in the users of ACEi/ARB, CCB, and α-blocker showed significant interaction effects. However, the smoking effect could not be eliminated in this analysis. DISCUSSION: Anti-hypertensive treatment was associated with a lower risk of lung cancer, which is associated with the anti-hypertensives exposure period. The potential interaction on the chemopreventive influence from combination usage of α-blocker and aspirin might exist. More corroborations on these findings are needed to focus on the different settings in future studies.

Progressive increases in creatine kinase activity in an anorexic cat with necrotising myopathy.

CASE SUMMARY: A 5-year-old castrated male domestic shorthair cat with weight loss and reduced appetite was evaluated for increased and progressively rising creatine kinase (CK) activity. The cat had recently been diagnosed with hepatic lipidosis. Muscle biopsy and histopathology revealed mild myonecrosis and phagocytosis without obvious inflammatory cell infiltrates. Resolution of necrotising myopathy was observed after a short course of anti-inflammatory prednisolone and nutritional supplementation. RELEVANCE AND NOVEL INFORMATION: This is the first report of a necrotising myopathy in a cat associated with progressively increasing CK activity and decreased appetite. Anorexia in cats has been associated with increased CK activity, but an underlying cause of this CK elevation has only been postulated. Here we document muscle necrosis and muscle stiffness in a cat with anorexia.

Efficacy and safety comparing prasugrel/ticagrelor and clopidogrel in Hong Kong post-acute coronary syndrome patients-A 10-year cohort study.

BACKGROUND: Clinical evidence of prasugrel/ticagrelor in dual antiplatelet therapy (DAPT) in Asian acute coronary syndrome (ACS) population remains inconclusive. We aimed to compare the clinical efficacy and safety of prasugrel/ticagrelor compared to clopidogrel as part of DAPT in Hong Kong ACS population for 10 years. HYPOTHESIS: Prasugrel/ticagrelor, compared to clopidogrel, reduces risk of major adverse cardiovascular event (MACE) in Hong Kong ACS population. METHODS: The retrospective observational cohort study included patients admitted to seven institutions under Hospital Authority Hong Kong with diagnosis of ACS during 2008-2017. Risk of MACE, defined as composite of cardiovascular (CV) death, non-fatal myocardial infarction (MI) and non-fatal stroke, and risk of any bleeding leading to hospitalization were examined. Baseline characteristics difference was adjusted by propensity score (PS) matching. Adjusted Cox regression model was used to estimate hazard ratio of interested outcome. RESULTS: In PS matched cohort including 944 patients in each group, MACE risk reduction of 40% from 1 year to 5 years after index ACS event was observed in prasugrel/ticagrelor group (HR 0.60, 95% CI 0.39-0.91, p = .015). The risk reduction was highly driven by MI reduction (HR 0.54, 95% CI 0.33-0.91, p = .019). Lower bleeding risk was observed in prasugrel/ticagrelor group compared to clopidogrel from 1 year to 5 years (HR 0.46, 95% CI 0.21-1.00, p = .051). CONCLUSIONS: Prasugrel/ticagrelor showed MACE risk reduction over clopidogrel as part of DAPT up to 5 years after index event, while prasugrel/ticagrelor was not associated with increased bleeding risk.

May Measurement Month 2017-2019: A Community-Wide Opportunistic Blood Pressure Screening Campaign in Hong Kong.

INTRODUCTION: Hypertension is a modifiable risk factor for multiple cardiovascular diseases. Early identification and intervention of new cases are crucial to improve patients' outcomes. May Measurement Month (MMM) is an annual global synchronised blood pressure (BP) screening campaign. Participants can have their BP measured at the screening sites. It may be a possible way to identify undiagnosed hypertensive patients in the population. METHODS: It was a cross-sectional study of BP among Hong Kong adults. Multiple screening sites were set in local community pharmacies and on the campus of the Chinese University of Hong Kong. Participants were asked to fill in a questionnaire regarding their demographics, medical history, and social history. Then, they took at least one BP reading using an automated sphygmomanometer after sitting at for 5 minutes. Up to three BP readings were taken and recorded for each participant, with one-minute intervals between readings. RESULTS: A total of 3224 adults participated in MMM between 2017 and 2019. The average BP among the 3224 participants was 139.8/75.5 mmHg. The prevalence of hypertension was 2282 (70.8%), of which 635 (27.8%) were undiagnosed before MMM. Among the 1647 participants previously diagnosed with hypertension, 1007 (61.1%) had uncontrolled hypertension. CONCLUSION: A high number of cases can be identified with untreated, or treated but uncontrolled, hypertension from MMM. Citizens should be encouraged to check BP regularly and take follow-up actions if hypertension is suspected.

Trends of prescribing adherence of antiplatelet agents in Hong Kong patients with acute coronary syndrome: a 10-year retrospective observational cohort study.

OBJECTIVES: The objective of this study is to examine the temporal trend of antiplatelet prescribing pattern during index hospitalisation discharge in Hong Kong (HK) acute coronary syndrome (ACS) population. DESIGN: The study is a retrospective observational cohort study. SETTING: The study retrieved data from electronic health record from Hospital Authority (HA), HK. PARTICIPANTS: The study included patients aged 18 years old or above, who were admitted to seven institutions under HA with diagnosis of ACS during 2008-2017. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the frequency of antiplatelet therapy prescription at the point of index hospitalisation discharge each year during 2008-2017. Association between demographics, baseline comorbidities, procedures and antiplatelet prescription were examined as secondary outcome using multivariate logistic regression model, with commonly used antiplatelet groups selected for comparison. RESULTS: Among the included 14 716 patients, 5888 (40.0%) discharged with aspirin alone, 6888 (46.8%) discharged with dual antiplatelet therapy (DAPT) with clopidogrel, and 973 (6.6%) discharged with DAPT with prasugrel/ticagrelor. Prescribing rate of aspirin alone decreased substantially from 56.8% in 2008 to 27.5% in 2017. Utilisation of DAPT with clopidogrel increased from 33.7% in 2008 to 52.7% in 2017. Use of DAPT with prasugrel/ticagrelor increased from 0.3% in 2010 to 15.3% in 2017. Compared with those prescribed with DAPT with clopidogrel, male patients (adjusted OR (aOR) 1.34, 95% CI 1.09 to 1.65), patients with non-ST-elevation myocardial infarction (aOR 2.50, 1.98 to 3.16) or ST-elevation myocardial infarction (aOR 3.26, 2.59 to 4.09), use of glycoprotein IIb/IIIa (aOR 3.03, 2.48 to 3.68) or undergoing percutaneous coronary intervention (aOR 3.85, 3.24 to 4.58) or coronary artery bypass graft (aOR 6.52, 4.63 to 9.18) during index hospitalisation, concurrent use of histamine-2 receptor antagonists (aOR 1.35, 1.10 to 1.65) or proton pump inhibitors (aOR 3.57, 2.93 to 4.36) during index hospitalisation discharge were more likely to be prescribed with DAPT with prasugrel/ticagrelor. Patients with older age (aOR 0.97, 0.96 to 0.97), diabetes (aOR 0.68, 0.52 to 0.88), chronic kidney disease (aOR 0.43, 0.22 to 0.85) or concurrent use of oral anticoagulant (aOR 0.16, 0.07 to 0.42) were more likely to received DAPT with clopidogrel. CONCLUSIONS: Use of DAPT with prasugrel/ticagrelor was suboptimal yet improving during 2008-2017 in HK patients with ACS. Considering DAPT, predictors for clopidogrel prescription, compared with prasugrel/ticagrelor, were consistent with identified risk factors of bleeding.

Use of metformin and aspirin is associated with delayed cancer incidence.

BACKGROUND: While the chemoprevention effect of aspirin is well-established, the effects of metformin in cancer prevention is still controversial. This study is to investigate the use of aspirin, metformin, or the combination of both is associated with delayed cancer incidence. METHOD: This dataset is based on the electronic medical record of public hospitals in Hong Kong. Patients were classified into 1. aspirin user, 2. metformin user, 3. both aspirin and metformin user and 4. control group with neither aspirin nor metformin used. Aspirin and/or metformin must have been taken for over 6 months in the treatment group and cancer incidences was counted at least 6 months after exposure to such medications. The primary outcome of this study was overall incidence of cancer during the follow-up period. The secondary outcomes were cancer incidences of specific sites, including colon/rectum, liver, oesophagus, pancreas, stomach, lung, breast, kidney, bladder and prostate. Cox proportional hazards regression models were fitted to estimate hazard ratios of cancer risks. Inverse probability of treatment weighting was used to control for the medication effects. RESULTS: A total of 120,971 aspirin users, 11,365 metformin users, and 6630 aspirin plus metformin users, were identified. Compare to the control groups, those who used aspirin alone demonstrated a significant reduction in overall cancer risk (HR 0.80, 95% CI 0.73-0.87). Similarly, those who used metformin alone also showed an overall reduction in cancer risk (HR 0.79, 95% CI 0.71-0.88). Patients who received both aspirin and metformin showed the most significant reduction in overall cancer risk (HR 0.53, 95% CI 0.45-0.63). Metformin showed a significant reduction in cancer risk of lung, oesophagus and bladder. CONCLUSION: There is a similar decrease in overall cancer rate with the use of aspirin or metformin alone. A more significant reduction in overall cancer risk was found with the use of both agents.

Warfarin control in Hong Kong clinical practice: a single-centre observational study.

INTRODUCTION: Time in therapeutic range (TTR) assesses the safety and effectiveness of warfarin therapy using the international normalised ratio. This study investigated the TTR in Hong Kong patients using both European and Japanese therapeutic ranges and patients' economic and clinical outcomes. Predictors of poor warfarin control and patient knowledge concerning warfarin therapy were assessed. METHODS: A 5-month observational study with retrospective and prospective components was conducted in the Prince of Wales Hospital. The study examined electronic patient records of patients who received warfarin for at least 1 year during the period from January 2010 to August 2015. Patient knowledge was assessed via phone interview using the Oral Anticoagulation Knowledge (OAK) test. RESULTS: In total, 259 patients were included; 174 completed the OAK test. The calculated mean TTR was 40.2±17.1% (European therapeutic range), compared with 49.1±16.1% (Japanese therapeutic range) [P<0.001]. Mean TTR was higher in patients with atrial fibrillation than in patients with prosthetic heart valve (P<0.001). The abilities of TTR to predict clinical and economic outcomes were comparable between European and Japanese therapeutic ranges. Patients with ideal TTR had fewer clinical complications and lower healthcare costs. Patients with younger age exhibited worse TTR, as did those with concurrent use of furosemide, famotidine, or simvastatin. Mean OAK test score was 54.1%. Only 24 (13.8%) patients achieved a satisfactory overall score of ≥75% in the test. CONCLUSION: Warfarin use in Hong Kong patients was poorly controlled, regardless of indication. Patient knowledge concerning warfarin use was suboptimal; thus, additional patient education is warranted regarding warfarin.

The Cardioprotective Role of Flaxseed in the Prevention of Doxorubicin- and Trastuzumab-Mediated Cardiotoxicity in C57BL/6 Mice.

BACKGROUND: Although the combination of doxorubicin (DOX) and trastuzumab (TRZ) reduces the progression and recurrence of breast cancer, these anticancer drugs are associated with significant cardiotoxic side effects. OBJECTIVE: We investigated whether prophylactic administration of flaxseed (FLX) and its bioactive components, α-linolenic acid (ALA) and secoisolariciresinol diglucoside (SDG), would be cardioprotective against DOX + TRZ-mediated cardiotoxicity in a chronic in vivo female murine model. METHODS: Wild-type C57BL/6 female mice (10-12 wk old) received daily prophylactic treatment with one of the following diets: 1) regular control (RC) semi-purified diet; 2) 10% FLX diet; 3) 4.4% ALA diet; or 4) 0.44% SDG diet for a total of 6 wks. Within each arm, mice received 3 weekly injections of 0.9% saline or a combination of DOX [8 mg/(kg.wk)] and TRZ [3 mg/(kg.wk)] starting at the end of week 3. The main outcome was to evaluate the effects of FLX, ALA, and SDG on cardiovascular remodeling and markers of apoptosis, inflammation, and mitochondrial dysfunction. Significance between measurements was determined using a 4 (diet) × 2 (chemotherapy) × 2 (time) mixed factorial design with repeated measures. RESULTS: In the RC + DOX + TRZ-treated mice at week 6 of the study, the left ventricular ejection fraction (LVEF) decreased by 50% compared with the baseline LVEF (P < 0.05). However, the prophylactic administration of the FLX, ALA, or SDG diet was partially cardioprotective, with mice in these treatment groups showing an ∼68% increase in LVEF compared with the RC + DOX + TRZ-treated group at week 6 (P < 0.05). Although markers of inflammation (nuclear transcription factor κB), apoptosis [poly (ADP-ribose) polymerase-1 and the ratio of BCL2-associated X protein to B-cell lymphoma-extra large], and mitochondrial dysfunction (BCL2-interacting protein 3) were significantly elevated by approximately 2-fold following treatment with RC + DOX + TRZ compared with treatment with RC + saline at week 6, prophylactic administration of FLX, ALA, or SDG partially downregulated these signaling pathways. CONCLUSION: In a chronic in vivo female C57BL/6 mouse model of DOX + TRZ-mediated cardiotoxicity, FLX, ALA, and SDG were partially cardioprotective.

Author Correction: First-hand, immersive full-body experiences with living cells through interactive museum exhibits.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.