Cardiovascular health of patients with cancer: Challenges abound.

Patients with cancer have elevated cardiovascular risks compared to those without cancer. As cancer incidence increases and cancer-related mortality decreases, cardiovascular diseases in patients with a history of cancer will become increasingly important. This in turn is reflected by the exponentially increasing amount of cardio-oncology research in recent years. This narrative review aims to summarize the key existing literature in several main areas of cardio-oncology, including the epidemiology, natural history, prevention, management, and determinants of the cardiovascular health of patients with cancer, and identify relevant gaps in evidence for further research.

Characterizing the Rhinoplasty Outcomes Most Important to Patients, Surgeons, and the General Population.

Understanding rhinoplasty characteristics important to patients, physicians, and society is essential for evaluating outcomes and designing optimal treatment plans. The authors aimed to elucidate specific rhinoplasty-related outcomes that are most important to patients, surgeons, and the general population. A cross-sectional survey comprising 11 rhinoplasty-specific characteristics, was distributed to patients, facial plastic surgeons, and the general population. Adult patients presenting for rhinoplasty consideration or follow-up after undergoing rhinoplasty were recruited. Characteristics rankings were compared between the 3 respondent groups using Spearman's rank correlation coefficient (ρ). Responses from 150 surgeons, 111 patients, and 102 lay individuals from the general population were included for analysis. When ranking rhinoplasty-specific characteristics in order of importance, patients and the general population ranked "ability to breathe through nose while awake" first and "overall appearance of nose" as second. Surgeons ranked "overall appearance of nose" first and "ability to breathe through nose while awake" second. There were strong correlations between patients' and surgeons' rankings (Spearman's ρ=0.836, P=0.002), between patients' and the general population's rankings (Spearman's ρ=0.773, P=0.007), and between surgeons' and the general population's rankings (Spearman's ρ=0.782, P=0.006). Our results highlight a significant correlation between characteristics of the "ideal" nose as determined by patients, surgeons, and the general population.

Epigenetic dissection of human blood group genes reveals regulatory elements and detailed characteristics of KEL and four other loci.

BACKGROUND: Blood typing is essential for safe transfusions and is performed serologically or genetically. Genotyping predominantly focuses on coding regions, but non-coding variants may affect gene regulation, as demonstrated in the ABO, FY and XG systems. To uncover regulatory loci, we expanded a recently developed bioinformatics pipeline for discovery of non-coding variants by including additional epigenetic datasets. METHODS: Multiple datasets including ChIP-seq with erythroid transcription factors (TFs), histone modifications (H3K27ac, H3K4me1), and chromatin accessibility (ATAC-seq) were analyzed. Candidate regulatory regions were investigated for activity (luciferase assays) and TF binding (electrophoretic mobility shift assay, EMSA, and mass spectrometry, MS). RESULTS: In total, 814 potential regulatory sites in 47 blood-group-related genes were identified where one or more erythroid TFs bound. Enhancer candidates in CR1, EMP3, ABCB6, and ABCC4 indicated by ATAC-seq, histone markers, and co-occupancy of 4 TFs (GATA1/KLF1/RUNX1/NFE2) were investigated but only CR1 and ABCC4 showed increased transcription. Co-occupancy of GATA1 and KLF1 was observed in the KEL promoter, previously reported to contain GATA1 and Sp1 sites. TF binding energy scores decreased when three naturally occurring variants were introduced into GATA1 and KLF1 motifs. Two of three GATA1 sites and the KLF1 site were confirmed functionally. EMSA and MS demonstrated increased GATA1 and KLF1 binding to the wild-type compared to variant motifs. DISCUSSION: This combined bioinformatics and experimental approach revealed multiple candidate regulatory regions and predicted TF co-occupancy sites. The KEL promoter was characterized in detail, indicating that two adjacent GATA1 and KLF1 motifs are most crucial for transcription.

The modified Rajan's heart failure risk score predicts all-cause mortality in patients hospitalized for heart failure with reduced ejection fraction: a retrospective cohort study.

Background: The dimensionless Rajan's heart failure (R-hf) risk score was proposed to predict all-cause mortality in patients hospitalized with chronic heart failure (HF) and reduced ejection fraction (EF) (HFrEF). Purpose: To examine the association between the modified R-hf risk score and all-cause mortality in patients with HFrEF. Methods: Retrospective cohort study included adults hospitalized with HFrEF, as defined by clinical symptoms of HF with biplane EF less than 40% on transthoracic echocardiography, at a tertiary centre in Dalian, China, between 1 November 2015, and 31 October 2019. All patients were followed up until 31 October 2020. A modified R-hf risk score was calculated by substituting brain natriuretic peptide (BNP) for N-terminal prohormone of BNP (NT-proBNP) using EF× estimated glomerular filtration rate (eGFR)× haemoglobin (Hb))/BNP. The patients were stratified into tertiles according to the R-hf risk score. The measured outcome was all-cause mortality. The score performance was assessed using C-statistics. Results: A total of 840 patients were analyzed (70.2% males; mean age, 64±14 years; median (interquartile range) follow-up 37.0 (27.8) months). A lower modified R-hf risk score predicted a higher risk of all-cause mortality, independent of sex and age [1st tertile vs. 3rd tertile: adjusted hazard ratio (aHR), 3.46; 95% CI: 2.11-5.67; P<0.001]. Multivariate Cox regression analysis indicated that a lower modified R-hf risk score was associated with increased cumulative all-cause mortality [univariate: (1st tertile vs. 3rd tertile: aHR, 3.45; 95% CI: 2.11-5.65; P<0.001) and multivariate: (1st tertile vs. 3rd tertile: aHR 2.21, 95% CI: 1.29-3.79; P=0.004)]. The performance of the model, as reported by C-statistic was 0.67 (95% CI: 0.62-0.72). Conclusion: The modified R-hf risk score predicted all-cause mortality in patients hospitalized with HFrEF. Further validation of the modified R-hf risk score in other cohorts of patients with HFrEF is needed before clinical application.

Epidemiology and patterns of gymnastics-related head & neck trauma injuries: A NEISS database study.

OBJECTIVE: To describe the epidemiology and patterns of gymnastics-related Head & Neck trauma injuries using the NEISS database from 2001 to 2020. STUDY DESIGN AND SETTING: Cross-sectional analysis of a national database. METHODS: Gymnastics-related ED visits between 2001 and 2020 were queried from the NEISS database. Bivariate chi-squared analyses were used to compare injury demographics, location, type, and disposition. Fracture location was identified using the narrative description of each case and were divided into subtypes for further analysis. RESULTS: 1455 gymnastics-related head and neck traumatic injuries were identified. The majority were in females (65.8%). The most common presenting age group was pediatric (≤18 years) (92.7%), and the largest racial group was Caucasian (51.5%). Of all location subtypes, facial injuries were the most common presenting injury type overall (45.2%). Regarding injury types, lacerations were most common (36.8%), followed by dental injury (30.7%) and fractures (21.2%). The most common location of head and neck fractures was the nose (45.8%), followed by cervical spine (16.7%) and orbit (13.3%). The majority (95.7%) of gymnastics-related head and neck traumatic injuries presenting to the ED were treated and discharged. CONCLUSION: This study characterizes gymnastics-related head and neck injuries which is a topic that is under-studied. The findings from this study are helpful for gymnasts and those who care for them including providers, coaches and guardians, and this data may help inform future guidelines for treatment and injury prevention.

Bioinformatic Study of Possible Acute Regulation of Acid Secretion in the Stomach.

The gastric H+,K+-ATPase is an integral membrane protein which derives energy from the hydrolysis of ATP to transport H+ ions from the parietal cells of the gastric mucosa into the stomach in exchange for K+ ions. It is responsible for the acidic environment of the stomach, which is essential for digestion. Acid secretion is regulated by the recruitment of the H+,K+-ATPase from intracellular stores into the plasma membrane on the ingestion of food. The similar amino acid sequences of the lysine-rich N-termini α-subunits of the H+,K+- and Na+,K+-ATPases, suggests similar acute regulation mechanisms, specifically, an electrostatic switch mechanism involving an interaction of the N-terminal tail with the surface of the surrounding membrane and a modulation of the interaction via regulatory phosphorylation by protein kinases. From a consideration of sequence alignment of the H+,K+-ATPase and an analysis of its coevolution with protein kinase C and kinases of the Src family, the evidence points towards a phosphorylation of tyrosine-7 of the N-terminus by either Lck or Yes in all vertebrates except cartilaginous fish. The results obtained will guide and focus future experimental research.

Identification of anti-fibrotic and pro-apoptotic bioactive compounds from Ganoderma formosanum and their possible mechanisms in modulating TGF-ß1-induced lung fibrosis.

ETHNOPHARMACOLOGICAL RELEVANCE: The Compendium of Materia Medica and the Classic of Materia Medica, the two most prominent records of traditional Chinese medicine, documented the therapeutic benefits of Ganoderma sinense particularly in addressing pulmonary-related ailments. Ganoderma formosanum, an indigenous subspecies of G. sinense from Taiwan, has demonstrated the same therapeutic properties. AIM OF THE STUDY: The aim of this study is to identify bioactive compounds and evaluate the potential of G. formosanum extracts as a novel treatment to alleviate pulmonary fibrosis (PF). Using an in-house drug screening platform, two-stage screening was performed to determine their anti-fibrotic efficacy. METHODS AND MATERIALS: G. formosanum was fractionated into four partitions by solvents of different polarities. To determine their antifibrotic and pro-apoptotic properties, the fractions were analyzed using two TGF-ß1-induced pulmonary fibrosis cell models (NIH-3T3) and human pulmonary fibroblast cell lines, immunoblot, qRT-PCR, and annexin V assays. Subsequently, transcriptomic analysis was conducted to validate the findings and explore possible molecular pathways. The identification of potential bioactive compounds was achieved through UHPLC-MS/MS analysis, while molecular interaction study was investigated by multiple ligands docking and molecular dynamic simulations. RESULTS: The ethyl acetate fraction (EAF) extracted from G. formosanum demonstrated substantial anti-fibrotic and pro-apoptotic effects on TGF-ß1-induced fibrotic models. Moreover, the EAF exhibited no discernible cytotoxicity. Untargeted UHPLC-MS/MS analysis identified potential bioactive compounds in EAF, including stearic acid, palmitic acid, and pentadecanoic acid. Multiple ligands docking and molecular dynamic simulations further confirmed that those bioactive compounds possess the ability to inhibit TGF-ß receptor 1. CONCLUSION: Potential bioactive compounds in G. formosanum were successfully extracted and identified in the EAF, whose anti-fibrotic and pro-apoptotic properties could potentially modulate pulmonary fibrosis. This finding not only highlights the EAF's potential as a promising therapeutic candidate to treat pulmonary fibrosis, but it also elucidates how Ganoderma confers pulmonary health benefits as described in the ancient texts.

One-pot synthesis of benzofused 8-oxabicyclo[3.3.1]nonanes via GaCl3-mediated cyclocondensation of o-allylbenzaldehydes and 1,3-dicarbonyl synthons.

GaCl3-mediated one-pot cyclocondensation of o-allylbenzaldehydes and 1,3-dicarbonyls generates benzofused 8-oxabicyclo[3.3.1]nonanes in moderate to good yields in refluxing MeNO2 under easy-operational conditions. A plausible mechanism is proposed and discussed here. In the overall reaction process, various metal chloride-promoted conditions were investigated for one-pot cyclocondensation.

A Narrative Review on Diabetic Ketoacidosis in Children.

BACKGROUND: Diabetic ketoacidosis (DKA) is a life-threatening complication in children with diabetes mellitus. There are considerable differences in the management approaches for DKA between different countries. One of the main areas of differences between guidelines is the administration of fluid, with most guidelines adopting a restrictive approach. This is based on the concern over cerebral oedema, a lethal sequela allegedly to be caused by excessive fluid administration. However, in recent years, new clinical studies suggest that there is no causal relationship between intravenous fluid therapy and DKA-related cerebral injury. The British Society of Paediatric Endocrinology updated its guideline in 2020 to adopt a more permissive approach to fluid administration, which has sparked controversy among some paediatricians. OBJECTIVES: The purpose of this article is to provide a narrative review on the management of DKA. METHODS: A PubMed search was performed with clinical queries using the key term "diabetic ketoacidosis". The search strategy included randomized controlled trials, clinical trials, meta-analyses, observational studies, guidelines, and reviews. The search was restricted to English literature and the age range of 18 years and younger. Moreover, we reviewed and compared major guidelines. CONCLUSION: The management of DKA involves early recognition, accurate diagnosis, meticulous fluid and insulin treatment with close monitoring of blood glucose, ketones, electrolytes, renal function, and neurological status. There is still limited clinical evidence to support either a restrictive or permissive approach in the fluid management of paediatric DKA patients. Clinicians should exercise caution when applying different guidelines in their clinical practice, considering the specific circumstances of individual paediatric patients.

Design of 2-Pyridone Fluorophores for Brighter Emissions at Longer Wavelengths.

The recent discovery of blue fluorophores with high quantum yields based on pyridone structures inspired the development of new low-molecular-weight fluorophores with bright emissions at tunable wavelengths, which are highly attractive for various applications. In this study, we propose a rational design strategy for 2-pyridone-based fluorophores with bright emissions at long wavelengths. With a detailed understanding of the positional substitution effects on each carbon atom of the 2-pyridone core, we developed a bright blue fluorophore (λabs =377 nm; λem =433 nm; ϵ=13,200 M-1 cm-1 ; ϕF =88 %) through C3 -aryl and C4 -ester substitutions followed by cyclization. Furthermore, by applying the intramolecular charge transfer (ICT) principle, we invented a bright green fluorophore through C3 - and C4 -diester and C6 -aryl substitutions. The ICT fluorophore based on the pyridone structure shows large molar absorptivity (ϵ=20,100 M-1 cm-1 ), longer emission wavelength (λem =539 nm), high emission quantum yield (ϕF =74 %), and large Stokes shift (Δv=5720 cm-1 ), which are comparable to those of practical fluorescent probes.

Demography, common disorders and mortality of Shih Tzu dogs under primary veterinary care in the UK.

BACKGROUND: Shih Tzus are a popular dog breed in the UK although there is relatively little reported information on their health. This study aimed to characterise the demography, common disorders and mortality of Shih Tzus under primary veterinary care during 2016 in the UK using de-identified clinical records from the VetCompass™ Programme. RESULTS: The study population of 336,865 dogs under veterinary care during 2016 included 11,082 Shih Tzus (3.3%). The median age was 4.1 years (IQR: 2.1-7.1, range: 0.3-20.4) and mean adult bodyweight was 7.9 kg (SD: 1.9 kg). Annual proportional births increased from 2.2% of all dog births in 2005 to 3.8% in 2013, dropping to 3.3% by 2016. From a random subset of 2,423 Shih Tzus that had information extracted on disorders diagnosed during 2016, the most prevalent fine-level precision disorders were periodontal disease (n = 229, prevalence 9.5%, 95% CI: 8.4-10.7), anal sac impaction (180, 7.4%, 95% CI: 6.5-8.5) and ear disorders (134, 5.5%, 95% CI: 4.7-6.5). The most prevalent grouped-level precision disorders were cutaneous (n = 402, prevalence: 16.6%, 95% CI: 15.2-18.1), dental (322, 13.3%, 95% CI: 12.0-14.7), and ophthalmological (289, 11.9%, 95% CI: 10.7-13.3). Males were more likely than females to be diagnosed with skin disorders (P = 0.007) and musculoskeletal disorders (P = 0.010) while females were more likely than males to be diagnosed with hernias (P = 0.005). The median age of death was 12.7 years (IQR 8.7-14.3, range 2.0-19.9) and did not differ statistically between males and females. The most common grouped causes of death were enteropathy (7.9%, 95% CI: 3.9-15.4), heart disease (7.9%, 95% CI: 3.9-15.4) and poor quality of life (7.9%, 95% CI: 3.9-15.4). CONCLUSIONS: Periodontal disease, anal sac impaction and ear disorders were identified as common health issues. Shih Tzus had higher prevalence of anal sac impaction, umbilical hernias and eye problems than reported previously in dogs overall, suggesting potential predispositions. Shih Tzus appear to be relatively long-lived compared to previous reports of lifespan in dogs overall. The results can inform veterinarians and owners on priority disorders for monitoring to protect welfare. Oral hygiene was highlighted as a healthcare priority.

The Shih Tzu is a popular small breed of dog in the UK. However, there is little information on common health conditions affecting this breed. This study aimed to describe the demography, common disorders, and causes of death of Shih Tzus in the UK in 2016 using the VetCompass™ Programme, which holds a database of anonymized clinical records of dogs attending primary-care veterinary practices in the UK.The study included 11,082 Shih Tzus (3.3%) from 336,865 dogs under veterinary care in the UK in VetCompass™ in 2016. The popularity of the Shih Tzu increased slightly from 2005 to 2013 but showed signs of decline towards 2016. The average age of Shih Tzus in the study was 4.1 years and the average adult bodyweight was 7.9 kg. The most common disorders affecting Shih Tzus in the study were periodontal disease (inflammation of the gums and tissue around the teeth, affecting 9.5% of Shih Tzus), anal sac impaction (7.4%) and ear disorders (5.5%). Male Shih Tzus were more likely than females to have skin and musculoskeletal disorders (conditions affecting bones, muscles and joints), while female Shih Tzus were more likely be diagnosed with hernias (when internal tissues push out through weakened muscle tissues). Shih Tzus had higher prevalence of anal sac impaction, umbilical hernias and eye problems than previously reported in dogs overall, suggesting potential predispositions. The average age at death of Shih Tzus was 12.7 years of age and the most common causes of death were enteropathy (gastrointestinal diseases causing signs such as diarrhoea and vomiting, 7.9%), heart disease (7.9%) and poor quality of life (7.9%).This study demonstrated the value of analysis of veterinary clinical records to increase our understanding of common health problems affecting dogs in the UK. The results can help both current and prospective Shih Tzu owners, and veterinarians, in prioritising preventative healthcare for Shih Tzus. For example, the most common disorder in Shih Tzus was periodontal disease, suggesting that increased preventative dental checkups and toothbrushing could improve welfare, especially if implemented from an early age.

4-(Triethoxysilyl)butanoic acid as a self-assembled monolayer for surface modification of titanium dioxide.

In this study, the carboxy silane 4-(triethoxysilyl)butanoic acid (TESBA) was used to modify titanium dioxide (TiO2) to create a self-assembled monolayer (SAM) and then directionally immobilize a capture antibody using protein A. We selected the amino silane (3-aminopropyl)triethoxysilane (APTES) to perform a comparative analysis with TESBA, and employed glutaraldehyde (GA) as the control. The modification and detection effects and the limit of detection (LOD) were evaluated by detecting human immunoglobulin G (IgG). The average normalized sensitivity of the dual-grating coupler waveguide biosensor was 49.63 ± 0.27 RIU-1 and the optimum resolution was 1.30 × 10-6 RIU. When the SAM was prepared using TESBA and APTES followed by GA, the LOD was 4.59 × 10-7 g mL-1 and 5.29 × 10-7 g mL-1, respectively. We analyzed the modification and detection effects by the t-test and concluded that the differences in the modification effects using TESBA and APTES followed by GA were significant and the differences in the detection effects using TESBA and APTES followed by GA were insignificant. The use of TESBA as the SAM led to the modification effect being superior to that obtained using APTES followed by GA. The detection effect using TESBA was as outstanding as that using APTES followed by GA. Our findings demonstrate the feasibility and effectiveness of using TESBA as the SAM to carboxylate the surface of TiO2, thereby enabling immobilization of biomolecules for human IgG detection.

Healthy diet intervention reverses the progression of NASH through gut microbiota modulation.

IMPORTANCE: The link between gut microbiota and diet is crucial in the development of non-alcoholic steatohepatitis (NASH). This study underscores the essential role of a healthy diet in preventing and treating NASH by reversing obesity, lipidemia, and gut microbiota dysbiosis. Moreover, the supplementation of functional food or drug to the diet can provide additional advantages by inhibiting hepatic inflammation through the modulation of the hepatic inflammasome signaling pathway and partially mediating the gut microbiota and lipopolysaccharide signaling pathway. This study highlights the importance of adopting healthy dietary habits in treating NASH and proposes that supplementing with ginger essential oil or obeticholic acid may offer additional benefits. Nonetheless, further clinical studies are necessary to validate these findings.

Treatment, Management, and Otolaryngology Consultation for Epistaxis in the Emergency Room: An Institutional Experience.

BACKGROUND: Epistaxis is a common reason for emergency department (ED) visits, accounting for approximately 1 of every 200 ED visits in the United States annually and up to one-third of all otolaryngology (ENT)-related ED encounters. OBJECTIVES: To detail reasons for ENT consultation for epistaxis in the ED, understand how consultation impacts patient care, assess follow-up patterns after emergency care, and study patient care after transfer or referral into the ED. METHODS: Retrospective chart review of 592 adult patients with epistaxis managed in a tertiary care ED setting between 2017 and 2018. Patients with known follow-up, ENT consult in the ED, or admission were included, while patients with trauma, recent head and neck surgery, or abnormal anatomy were excluded. RESULTS: The most common reasons for ENT consultation for epistaxis were for advanced management, referral to the ED from an outside facility or provider, and recent head and neck surgery. In total, 48.2% of patients treated for epistaxis in the ED received an ENT consultation. ENT consultation was associated with a higher likelihood of receiving absorbable or nonabsorbable packing (92.4% vs 36.1%). In total, 40.4% of patients referred into the ED from an outside facility or provider had no change in their management after receiving an ENT consult. Patients referred to the ED and White patients were significantly more likely to receive an ENT consult. Secondary analyses revealed that more White patients had an established outpatient ENT provider than patients of other races. On multivariate analysis, patients who received an ENT consult spent 75.2 min longer in the ED. CONCLUSION: The high percentage of patients referred or transferred to the ED for epistaxis management with no change in interventions after ENT consultation indicates a continued need to develop more precise clinical care pathways. Additionally, there may be gaps between White and non-White patients in access to ENT care.

Major adverse cardiovascular events of enzalutamide versus abiraterone in prostate cancer: a retrospective cohort study.

BACKGROUND: While the cardiovascular risks of androgen receptor pathway inhibitors have been studied, they were seldom compared directly. This study compares the risks of major adverse cardiovascular events (MACE) between enzalutamide and abiraterone among prostate cancer (PCa) patients. METHODS: Adult PCa patients receiving either enzalutamide or abiraterone in addition to androgen deprivation therapy in Hong Kong between 1 December 1999 and 31 March 2021 were identified in this retrospective cohort study. Patients who switched between enzalutamide and abiraterone, initiated abiraterone used without steroids, or experienced prior cardiac events were excluded. Patients were followed-up until 30 September 2021. The primary outcomes were MACE, a composite of stroke, myocardial infarction (MI), Heart failure (HF), or all-cause mortality and a composite of adverse cardiovascular events (CACE) not including all-cause mortality. The secondary outcomes were individual components of MACE. Inverse probability treatment weighting was used to balance covariates between treatment groups. RESULTS: In total, 1015 patients were analyzed (456 enzalutamide users and 559 abiraterone users; mean age 70.6 ± 8.8 years old) over a median follow-up duration of 11.3 (IQR: 5.3-21.3) months. Enzalutamide users had significantly lower risks of 4P-MACE (weighted hazard ratio (wHR) 0.71 [95% confidence interval (CI) 0.59-0.86], p < 0.001) and CACE (wHR 0.63 [95% CI: 0.42-0.96], p = 0.031), which remained consistent in multivariable analysis. Such an association may be stronger in patients aged ≥65 years or without diabetes mellitus and was independent of bilateral orchidectomy. Enzalutamide users also had significantly lower risks of MI (wHR 0.57 [95% CI: 0.33-0.97], p = 0.040) and all-cause mortality (wHR 0.71 [95% CI: 0.59-0.85], p < 0.001). CONCLUSION: Enzalutamide was associated with lower cardiovascular risks than abiraterone in PCa patients.

Trends in Head and Neck Injuries Related to Electric Versus Pedal Bicycle Use in the United States.

OBJECTIVES: To describe the incidence of head and neck trauma related to electric bicycles and to characterize head and neck injury patterns seen in electric bicycle (eBike) users versus pedal bicyclists in the United States. METHODS: The National Electronic Injury Surveillance System (NEISS) was queried from 2009 to 2020 for patients with head and neck injuries related to electric and pedal bicycles. Extracted data included patient demographics, injury patterns, hospital admission, and helmet use. Univariate chi-squared analyses were performed to compare demographics and injury patterns between bicycle groups. Effect sizes were reported with Cramer V values (V). RESULTS: The incidence of eBike-related head and neck injuries increased from 2993 in 2009 to 9916 in 2020. Compared to pedal bicycle users, eBike users were more likely to have head injuries (60.4% vs. 52.0%) and fractures (10.9% vs. 6.0%), and were more likely to require hospitalization (20.6% vs. 10.4%). The effect size of helmet use was significantly greater in eBike users compared to pedal bicyclists when examining distributions of age group (V = 0.203 vs. V = 0.079), injury location (V = 0.220 vs. V = 0.082), and injury type (V = 0.162 vs. V = 0.059). Helmeted injuries in eBike users more commonly involved neck injuries and sprains, rather than head injuries and fractures. CONCLUSION: Head and neck trauma related to eBike use is increasing in the United States. Injury patterns and admission rates reflect greater injury severity in eBike users compared to pedal bicyclists. Helmet use may be particularly beneficial in mitigating head and neck injury in eBike users. LEVEL OF EVIDENCE: 3 Laryngoscope, 2023.

Statin use and mortality risk in Asian patients with prostate cancer receiving androgen deprivation therapy: A population-based cohort study.

BACKGROUND: This study aimed to examine the associations between the use of statins concurrent with androgen deprivation therapy (ADT) and the risks of mortality in Asian patients diagnosed with prostate cancer (PCa). METHODS: Adult patients (≥18 years old) diagnosed with PCa who were receiving any form of ADT and were being treated at public hospitals in Hong Kong from December 1999 to March 2021 were retrospectively identified, with follow-up conducted until September 2021. Patients who had received medical castration for <180 days without subsequent bilateral orchidectomy, those who had used statins concurrently with ADT for <180 days, and those with missing baseline total cholesterol levels were excluded. Statin users were defined as individuals who had used statins for ≥180 days concurrent with ADT, while non-users were those who had not used any statins. PCa-related mortality was the primary outcome, while all-cause mortality served as the secondary outcome. Inverse probability treatment weighting was employed to balance the covariates. RESULTS: A total of 4920 patients were included, consisting of 2578 statin users and 2342 non-users (mean age 76.1 ± 8.2 years). Over a mean follow-up period of 4.2 ± 3.3 years, it was observed that statin users had significantly lower risks of both PCa-related mortality (weighted hazard ratio [wHR] 0.56 [95% confidence interval (CI) 0.48, 0.65], p < 0.001) and all-cause mortality (wHR 0.57 [95% CI 0.51, 0.63], p < 0.001), regardless of the type of ADT used. Notably, these associations were more pronounced among patients with less advanced PCa, as indicated by the absence of androgen receptor antagonist or chemotherapy usage (p value for interaction <0.001 for both outcomes). CONCLUSION(S): The use of statins concurrent with ADT was associated with reduced mortality risks among Asian patients with PCa. These findings suggest the need for additional research to explore the potential role of statins in the treatment of PCa patients.

High-Complexity One-Pot Golden Gate Assembly.

Golden Gate Assembly is a flexible method of DNA assembly and cloning that permits the joining of multiple fragments in a single reaction through predefined connections. The method depends on cutting DNA using a Type IIS restriction enzyme, which cuts outside its recognition site and therefore can generate overhangs of any sequence while separating the recognition site from the generated fragment. By choosing compatible fusion sites, Golden Gate permits the joining of multiple DNA fragments in a defined order in a single reaction. Conventionally, this method has been used to join five to eight fragments in a single assembly round, with yield and accuracy dropping off rapidly for more complex assemblies. Recently, we demonstrated the application of comprehensive measurements of ligation fidelity and bias data using data-optimized assembly design (DAD) to enable a high degree of assembly accuracy for very complex assemblies with the simultaneous joining of as many as 52 fragments in one reaction. Here, we describe methods for applying DAD principles and online tools to evaluate the fidelity of existing fusion site sets and assembly standards, selecting new optimal sets, and adding fusion sites to existing assemblies. We further describe the application of DAD to divide known sequences at optimal points, including designing one-pot assemblies of small genomes. Using the T7 bacteriophage genome as an example, we present a protocol that includes removal of native Type IIS sites (domestication) simultaneously with parts generation by PCR. Finally, we present recommended cycling protocols for assemblies of medium to high complexity (12-36 fragments), methods for producing high-quality parts, examples highlighting the importance of DNA purity and fragment stoichiometric balance for optimal assembly outcomes, and methods for assessing assembly success. © 2023 New England Biolabs, Inc. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Assessing the fidelity of an overhang set using the NEBridge Ligase Fidelity Viewer Basic Protocol 2: Generating a high-fidelity overhang set using the NEBridge GetSet Tool Alternate Protocol 1: Expanding an existing overhang set using the NEBridge GetSet Tool Basic Protocol 3: Dividing a genomic sequence with optimal fusion sites using the NEBridge SplitSet Tool Basic Protocol 4: One-pot Golden Gate Assembly of 12 fragments into a destination plasmid Alternate Protocol 2: One-pot Golden Gate Assembly of 24+ fragments into a destination plasmid Basic Protocol 5: One-pot Golden Gate Assembly of the T7 bacteriophage genome from 12+ parts Support Protocol 1: Generation of high-purity amplicons for assembly Support Protocol 2: Cloning assembly parts into a holding vector Support Protocol 3: Quantifying DNA concentration using a Qubit 4 fluorometer Support Protocol 4: Visualizing large assemblies via TapeStation Support Protocol 5: Validating phage genome assemblies via ONT long-read sequencing.