Liquid biomarkers in prostate cancer: recent advancements and future directions.

PURPOSE OF REVIEW: Traditional diagnostic approaches of prostate cancer like PSA are limited by high false-positive rates and insufficient capture of tumour heterogeneity, necessitating the development of more precise tools. This review examines the latest advancements in liquid biomarkers for prostate cancer, focusing on their potential to refine diagnostic accuracy and monitor disease progression. RECENT FINDINGS: Liquid biomarkers have gained prominence because of their minimally invasive nature and ability to reflect the molecular characteristics of prostate cancer. Circulating tumour cells provide insight into tumour cell dissemination and are indicative of aggressive disease phenotypes, with single-cell analyses revealing genomic instability and treatment resistance. Circulating tumour DNA offers real-time tumour genomic information, aiding in treatment decision-making in advanced prostate cancer, where it has been associated with clinical progression. MicroRNAs act as oncogenes or tumour suppressors and exhibit diagnostic and prognostic potential; however, their clinical utility is constrained by the lack of consistent validation. Extracellular vesicles contain tumour-derived biomolecules, with specific proteins demonstrating prognostic relevance. Applications of these markers to urinary testing have been demonstrated. SUMMARY: Liquid biomarkers show potential in refining prostate cancer management. Future research should aim to integrate these biomarkers into a cohesive framework in line with precision medicine principles.

Epidemic-specific association of maternal exposure to per- and polyfluoroalkyl substances (PFAS) and their components with maternal glucose metabolism: A cross-sectional analysis in a birth cohort from Hong Kong.

Per- and polyfluoroalkyl substances (PFAS) are persistent chemicals that have been linked to increased risk of gestational diabetes mellitus (GDM) and may affect glucose metabolisms during pregnancy. We examined the associations between maternal PFAS exposure and maternal glucose metabolisms and GDM risk among 1601 mothers who joined the Hyperglycaemia-and-Adverse-Pregnancy-Outcome (HAPO) Study in Hong Kong in 2001-2006. All mothers underwent a 75 g-oral-glucose-tolerance test at 24-32 weeks of gestation. We measured serum concentrations of six PFAS biomarkers using high-performance liquid-chromatography-coupled-with-tandem-mass-spectrometry (LC-MS-MS). We fitted conventional and advanced models (quantile-g-computation [qgcomp] and Bayesian-kernel machine regression [BKMR]) to assess the associations of individual and a mixture of PFAS with glycaemic traits. Subgroup analyses were performed based on the enrollment period by the severe-acute-respiratory-syndrome (SARS) epidemic periods in Hong Kong between March 2003 and May 2004. PFOS and PFOA were the main components of PFAS mixture among 1601 pregnant women in the Hong Kong HAPO study, with significantly higher median PFOS concentrations (19.09 ng/mL), compared to Chinese pregnant women (9.40 ng/mL) and US women (5.27 ng/mL). Maternal exposure to PFAS mixture was associated with higher HbA1c in the qgcomp (ß = 0.04, 95 % CI: 0.01-0.06) model. We did not observe significant associations of PFAS mixture with fasting plasma glucose (PG), 1-h and 2-h PG in either model, except for 2-h PG in the qgcmop model (ß = 0.074, 95 % CI: 0.01-0.15). PFOS was the primary contributor to the overall positive effects on HbA1c. Epidemic-specific analyses showed specific associations between PFAS exposure and the odds of GDM in the pre-SARS epidemic period. The median concentration of PFOS was highest during the peri-SARS epidemic (21.2 [14.5-43.6] ng/mL) compared with the pre-SARS (12.3 [9.2-19.9] ng/mL) and post-SARS (20.3 [14.2-46.3] ng/mL) epidemic periods. Potential interactions and exposure-response relationships between PFOA and PFNA with elevated HbA1c were observed in the peri-SARS period in BKMR model. Maternal exposure to PFAS mixture was associated with altered glucose metabolism during pregnancy. SARS epidemic-specific associations call for further studies on its long-term adverse health effects, especially potential modified associations by lifestyle changes during the COVID-19 pandemic.

PFOS-elicited metabolic perturbation in liver and fatty acid metabolites in testis of adult mice.

Introduction: Multiple factors can contribute to sub-fecundity, including genetics, lifestyle, and environmental contaminants. PFASs are characterized as "forever chemicals" due to their ubiquitous contamination and their persistence in the environment, wildlife, and humans. Numerous studies have demonstrated that PFAS exposure adversely affects multiple bodily functions, including liver metabolism and gonadal function. It is unclear, however, how the disruption of hepatic fatty acid metabolism affects testicular function. Methods: In this study, male mice were administered 0.3 and 3 µg/g body weight of PFOS for 21 days. Results: Our data showed that PFOS exposure caused hepatic steatosis, as evidenced by significant increases in triglyceride levels, expression of ATP-citrate lyase, and fatty acid synthase, as well as fasting insulin levels. PFOS perturbed the expression levels of hepatokines, of which fibroblast growth factor-21 (Fgf-21), leukocyte cell-derived chemotaxin-2 (Lect-2), and retinol-binding protein-4 (Rbp-4) were significantly reduced, whereas angiopoietin-like 4 (Angptl4) was noticeably increased. While Rbp-4 and Fgf-21 are known to contribute to spermatogenesis and testosterone synthesis. In PFOS-exposed groups, testicular ATP, and testosterone decreased significantly with a significant increase in the expression of peroxisome proliferator-activated receptor-coactivator 1α. Mass spectrophotometry imaging revealed the localization of PFOS in testes, along with significant increases in fatty acid metabolites. These included arachidonic acid, dihomo-α-linolenic acid, dihomo-γ-linolenic acid, oxidized ceramide, diacylglycerol, phosphatidylcholine, and phosphatidylethanolamine, which are associated with inflammation and post-testicular causes of infertility. Discussion: This study revealed potential links between PFOS-elicited changes in hepatic metabolism and their impacts on testicular biology. This study provides insights into alternative targets elicited by PFOS that can be used to develop diagnostic and therapeutic strategies for improving testicular dysfunction.

Effects of In Utero PFOS Exposure on Epigenetics and Metabolism in Mouse Fetal Livers.

Prenatal exposure to perfluorooctanesulfonate (PFOS) increases fetus' metabolic risk; however, the investigation of the underlying mechanism is limited. In this study, pregnant mice in the gestational days (GD, 4.5-17.5) were exposed to PFOS (0.3 and 3 µg/g of body weight). At GD 17.5, PFOS perturbed maternal lipid metabolism and upregulated metabolism-regulating hepatokines (Angptl4, Angptl8, and Selenop). Mass-spectrometry imaging and whole-genome bisulfite sequencing revealed, respectively, selective PFOS localization and deregulation of gene methylation in fetal livers, involved in inflammation, glucose, and fatty acid metabolism. PCR and Western blot analysis of lipid-laden fetal livers showed activation of AMPK signaling, accompanied by significant increases in the expression of glucose transporters (Glut2/4), hexose-phosphate sensors (Retsat and ChREBP), and the key glycolytic enzyme, pyruvate kinase (Pk) for glucose catabolism. Additionally, PFOS modulated the expression levels of PPARα and PPARγ downstream target genes, which simultaneously stimulated fatty acid oxidation (Cyp4a14, Acot, and Acox) and lipogenesis (Srebp1c, Acaca, and Fasn). Using human normal hepatocyte (MIHA) cells, the underlying mechanism of PFOS-elicited nuclear translocation of ChREBP, associated with a fatty acid synthesizing pathway, was revealed. Our finding implies that in utero PFOS exposure altered the epigenetic landscape associated with dysregulation of fetal liver metabolism, predisposing postnatal susceptibility to metabolic challenges.

Environmental-relevant bisphenol A exposure promotes ovarian cancer stemness by regulating microRNA biogenesis.

Bisphenol A (BPA) is a ubiquitous environmental xenobiotic impacting millions of people worldwide. BPA has long been proposed to promote ovarian carcinogenesis, but the detrimental mechanistic target remains unclear. Cancer stem cells (CSCs) are considered as the trigger of tumour initiation and progression. Here, we show for the first time that nanomolar (environmentally relevant) concentration of BPA can markedly increase the formation and expansion of ovarian CSCs concomitant. This effect is observed in both oestrogen receptor (ER)-positive and ER-defective ovarian cancer cells, suggesting that is independent of the classical ERs. Rather, the signal is mediated through alternative ER G-protein-coupled receptor 30 (GPR30), but not oestrogen-related receptor α and γ. Moreover, we report a novel role of BPA in the regulation of Exportin-5 that led to dysregulation of microRNA biogenesis through miR-21. The use of GPR30 siRNA or antagonist to inhibit GPR30 expression or activity, respectively, resulted in significant inhibition of ovarian CSCs. Similarly, the CSCs phenotype can be reversed by expression of Exportin-5 siRNA. These results identify for the first time non-classical ER and microRNA dysregulation as novel mediators of low, physiological levels of BPA function in CSCs that may underlie its significant tumour-promoting properties in ovarian cancer.

Urinary continence in high-risk prostate cancer after robot-assisted radical prostatectomy.

PURPOSE OF REVIEW: Urinary incontinence is common postoperative complication following robot-assisted radical prostatectomy (RARP) in patients with prostate cancer (PCa). Despite the increasing adoption of RARP in the treatment of high-risk PCa (HRPC), concerns persist regarding the adequacy of reported continence outcomes in this subgroup. This review aims to illuminate the state of continence recovery in HRPC patients post-RARP. RECENT FINDINGS: Urinary continence (UC) recovery rates in HRPC was reported to be lower than the intermediate/low-risk counterparts from 6 to 24 months post-RARP. Predictive models showed that age, obesity, race, disease status, and surgical approaches represent predictors of continence recovery. Special techniques like NeuroSAFE technique and Retzius-Sparing approach also play a role in reducing incontinence also in the high-risk scenario. SUMMARY: RARP for HRPC appears to be associated with worse continence compared with other risk groups. A multimodality approach for prediction and prevention of incontinence after RARP is vital. Further research into this area is necessary to enhance continence recovery outcomes in HRPC patients undergoing RARP.

Incidence and Predictors for Oncologic Etiologies in Chinese Children with Pituitary Stalk Thickening.

BACKGROUND: With the increasing use of magnetic resonance imaging (MRI) in the evaluation of children with endocrine disorders, pituitary stalk thickening (PST) poses a clinical conundrum due to the potential for underlying neoplasms and challenges in obtaining a tissue biopsy. The existing literature suggests Langerhans cell histiocytosis (LCH) to be the commonest (16%) oncologic cause for PST, followed by germ cell tumors (GCTs, 13%) (CCLG 2021). As the cancer epidemiology varies according to ethnicity, we present herein the incidence and predictors for oncologic etiologies in Hong Kong Chinese children with PST. METHODS: Based on a territory-wide electronic database, we reviewed patients aged < 19 years who presented to three referral centers with endocrinopathies between 2010 and 2022. Records for patients who underwent at least one MRI brain/pituitary were examined (n = 1670): those with PST (stalk thickness ≥ 3 mm) were included, while patients with pre-existing cancer, other CNS and extra-CNS disease foci that were diagnostic of the underlying condition were excluded. RESULTS: Twenty-eight patients (M:F = 10:18) were identified. The median age at diagnosis of PST was 10.9 years (range: 3.8-16.5), with central diabetes insipidus (CDI) and growth hormone deficiency (GHD) being the most frequent presenting endocrine disorders. At a median follow-up of 4.8 years, oncologic diagnoses were made in 14 patients (50%), including 13 GCTs (46%; germinoma = 11, non-germinoma = 2) and one LCH (4%). Among patients with GCTs, 10 were diagnosed based on histology, two by abnormal tumor markers and one by a combination of histology and tumor markers. Three patients with germinoma were initially misdiagnosed as hypophysitis/LCH. The cumulative incidence of oncologic diagnoses was significantly higher in boys and patients with PST at presentation ≥6.5 mm, CDI or ≥2 pituitary hormone deficiencies at presentation and evolving hypopituitarism (all p < 0.05 by log-rank). CONCLUSIONS: A higher rate of GCTs was observed in Chinese children with endocrinopathy and isolated PST. The predictors identified in this study may guide healthcare providers in Asia in clinical decision making. Serial measurement of tumor markers is essential in management.

Tolerability of ifosfamide-containing regimen in patients with high-risk renal and INI-1-deficient tumors.

BACKGROUND: Outcomes for children with high-risk renal (HRR) and INI-1-deficient (INI-) tumors are unacceptably poor. Concerns about excessive toxicity-as many are infants and/or undergo nephrectomy-have resulted in decreased chemotherapy dosing and omission of the nephrotoxic drug ifosfamide in collaborative group studies. As cause of death for children with these cancers remains overwhelmingly more from progressive disease rather than treatment toxicity, we examined the tolerability of an intensive ifosfamide-containing regimen. PROCEDURE: Retrospective review of children with HRR/INI- tumors treated at a single institution with vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide, carboplatin, etoposide (VDC-ICE) from 2006-2016. The primary outcome was regimen tolerability, including kidney injury and grade 3-5 nonhematologic toxicities. RESULTS: Fourteen patients with a median age of 1.7 years (range: 0.1-10.5) treated with VDC-ICE were identified. Diagnosis included malignant rhabdoid tumor (n = 9) (primary renal [n = 2]); diffuse anaplastic Wilms tumor (n = 3); clear cell sarcoma of the kidney (n = 1); and anaplastic chordoma (n = 1). All children with primary renal tumors (43%) underwent complete (n = 5) or partial nephrectomy (n = 1) before chemotherapy. Nine (64%) completed all intended cycles of chemotherapy; n = 5 (36%) did not due to disease progression. Unplanned hospitalizations occurred in 13 (93%) patients, most commonly for febrile neutropenia. No patient experienced severe organ toxicity, diminished renal function, treatment discontinuation due to toxicities, or treatment-related death. CONCLUSIONS: In children with HRR/INI- tumors, VDC-ICE chemotherapy was well-tolerated without excessive toxicities, even amongst young patients with solitary kidneys. Concerns about toxicity should not preclude an intensive ifosfamide-containing regimen from use in future trials in this population.

Improving Home Caregiver Independence With Central Line Care for Pediatric Cancer Patients.

OBJECTIVE: Home caregivers (eg parents) of pediatric patients with cancer with external central lines (CL) must carefully maintain this device to prevent complications. No guidelines exist to support caregiver skill development, assess CL competency, follow-up after initial CL teaching, and support progress over time. We aimed to achieve >90% caregiver independence with CL care within 1 year through a family-centered quality improvement intervention. METHODS: Drivers to achieve CL care independence were identified using surveys and interviews of patient or caregivers, a multidisciplinary team with patient or family representatives, and piloting clinic return demonstrations (teach-backs). A family-centered CL care skill-learning curriculum, with a postdischarge teach-back program, was implemented using plan-do-study-act cycles. Patients or caregivers participated until independent with CL flushing. Changes included: language iterations to maximize patient or caregiver engagement, developing standardized tools for home use and for teaching and evaluating caregiver proficiency on the basis of number of nurse prompts required during the teach-back, earlier inpatient training, and clinic redesign to incorporate teach-backs into routine visits. The proportion of eligible patients whose caregiver had achieved independence in CL flushing was the outcome measure. Teach-back program participation was a process measure. Statistical process control charts tracked change over time. RESULTS: After 6 months of quality improvement intervention, >90% of eligible patients had a caregiver achieve independence with CL care. This was sustained for 30 months postintervention. Eighty-eight percent of patients (n = 181) had a caregiver participate in the teach-back program. CONCLUSION: A family-centered hands-on teach-back program can lead to caregiver independence in CL care.

Developing the Key Driver Diagram by Analyzing Home Central Line Caregiver Proficiency Factors.

Caregivers of pediatric oncology and stem cell transplant patients often care for central lines (CLs) at home. Methods to achieve caregiver CL care proficiency, and interventions designed with caregiver input are lacking. Methods: Caregivers of pediatric oncology and stem cell transplant patients patients with an external CL or removed within 2 weeks were eligible for a survey assessing knowledge, the value of training strategies, and comfort. We mapped responses (n = 79) and acceptability/challenges of introducing a pilot caregiver CL teach-back clinic program onto the capability, opportunity, motivation behavioral (COM-B) model of change to identify drivers of caregiver CL care proficiency. A working group, including caregivers, refined and approved a final driver diagram. Results: Survey: Ninety-four percent of caregivers answered knowledge questions correctly (capability); 95% considered hands-on training helpful (opportunity); 53% were not very comfortable with CL care (motivation). Teach-back: Seventy-nine percent of caregivers were interested in a teach-back as additional training; 38% participated (opportunity); 20% refused participation due to being overwhelmed/not having time (motivation). Thirty-three percent of participants had a CL proficiency assessment (capability). Drivers of home caregiver CL care proficiency included: support for the caregiver's physical capability to perform CL care; enabling the CL care nurse trainer role; facilitating and increasing training opportunities, and engaging caregivers early and continuously to motivate proficiency development appropriately. Conclusions: An approach centered on caregivers as main stakeholders can identify drivers to co-design an intervention for improved home CL care delivery. A standardized process to train and evaluate caregivers with multiple hands-on opportunities might be beneficial.

Adverse metabolic consequences of androgen deprivation therapy (ADT) on Asian patients with prostate cancer: Primary results from the real-life experience of ADT in Asia (READT) study.

BACKGROUND: Androgen deprivation therapy (ADT) use in prostate cancer (PCa) has seen a rising trend. We investigated the relationship between ADT and adverse changes in metabolic parameters in an Asian population. METHODS: This is an international prospective multicenter single-arm cohort yielded from the real-life experience of ADT in Asia (READT) registry. Consecutive ADT-naïve patients diagnosed of PCa and started on ADT were prospectively recruited from 2016 and analyzed. Baseline patient characteristics, PCa disease status, and metabolic parameters were documented. Patients were followed up at 6-month interval for up to 5 years. Metabolic parameters including body weight, lipid profiles, and glycemic profiles were recorded and analyzed. RESULTS: 589 patients were eligible for analysis. ADT was associated with adverse glycemic profiles, being notable at 6 months upon ADT initiation and persisted beyond 1 year. Comparing to baseline, fasting glucose level and hemoglobin A1c level increased by 4.8% (p < 0.001) and 2.7% (p < 0.001), respectively. Triglycerides level was also elevated by 16.1% at 6th month and by 20.6% at 12th month compared to baseline (p < 0.001). Mean body weight was 1.09 kg above baseline at 18th month (p < 0.001). CONCLUSION: ADT was associated with adverse metabolic parameters in terms of glycemic profiles, lipid profiles, and body weight in the Asian population. These changes developed early in the treatment and can persist beyond the first year. Regular monitoring of the biochemical profiles during treatment is paramount in safeguarding the patients' metabolic health.

Cadmium Disrupted ER Ca2+ Homeostasis by Inhibiting SERCA2 Expression and Activity to Induce Apoptosis in Renal Proximal Tubular Cells.

Cadmium (Cd2+) exposure induces chronic kidney disease and renal cancers, which originate from injury and cancerization of renal tubular cells. Previous studies have shown that Cd2+ induced cytotoxicity by disrupting the intracellular Ca2+ homeostasis that is physically regulated by the endoplasmic reticulum (ER) Ca2+ store. However, the molecular mechanism of ER Ca2+ homeostasis in Cd2+-induced nephrotoxicity remains unclear. In this study, our results firstly revealed that the activation of calcium-sensing receptor (CaSR) by NPS R-467 could protect against Cd2+ exposure-induced cytotoxicity of mouse renal tubular cells (mRTEC) by restoring ER Ca2+ homeostasis through the ER Ca2+ reuptake channel sarco/endoplasmic reticulum Ca2+-ATPase (SERCA). Cd2+-induced ER stress and cell apoptosis were effectively abrogated by SERCA agonist CDN1163 and SERCA2 overexpression. In addition, in vivo, and in vitro results proved that Cd2+ reduced the expressions of SERCA2 and its activity regulator phosphorylation phospholamban (p-PLB) in renal tubular cells. Cd2+-induced SERCA2 degradation was suppressed by the treatment of proteasome inhibitor MG132, which suggested that Cd2+ reduced SERCA2 protein stability by promoting the proteasomal protein degradation pathway. These results suggested that SERCA2 played pivotal roles in Cd2+-induced ER Ca2+ imbalance and stress to contribute to apoptosis of renal tubular cells, and the proteasomal pathway was involved in regulating SERCA2 stability. Our results proposed a new therapeutic approach targeting SERCA2 and associated proteasome that might protect against Cd2+-induced cytotoxicity and renal injury.

Iron Deficiency among School-Aged Adolescents in Hong Kong: Prevalence, Predictors, and Effects on Health-Related Quality of Life.

Iron deficiency (ID) is a prevalent nutritional deficiency affecting children/adolescents worldwide. We reported (1) the prevalence of ID and ID with anemia (IDA) among Chinese school-aged adolescents, (2) clinical and dietary predictors of iron status, and (3) its impact on health-related qualities of life (HRQoL). This cross-sectional study recruited 183 boys and 340 girls (mean age = 17.55) from 16 schools in Hong Kong. ID is defined as serum ferritin <15 µg/L. The participants reported their dietary habits, menstrual patterns (girls), and HRQoL using structured questionnaires. The overall prevalence of ID was 11.1%. None of the boys had ID or IDA. Among girls, the rate of ID was 17.1% and IDA was 10.9%. One-third (36.3%) reported a regular habit of skipping ≥1 meal/day. Lower ferritin was found in adolescents who skipped meals (Est = -35.1, p = 0.017). Lower ferritin is correlated with poorer school functioning (Est = 0.81, p = 0.045) and fatigue (Est = 0.92, p = 0.016). Skipping meals is associated with poorer physical (p = 0.0017) and school functioning (p = 0.027). To conclude, 1 in 10 school-aged adolescents in Hong Kong are iron-deficient. The ID rate in girls (17.1%) is similar to that in other industrialized countries (5.2-16.6%). Future work should promote awareness on the potential health consequences of poor dietary habits on ID and the well-being of adolescents.

Preventable harm because of outpatient medication errors among children with leukemia and lymphoma: A multisite longitudinal assessment.

BACKGROUND: There is little longitudinal information about the type and frequency of harm resulting from medication errors among outpatient children with cancer. We aimed to characterize rates and types of medication errors and harm to outpatient children with leukemia and lymphoma over 7 months of treatment. METHODS: We recruited children taking medications at home for leukemia or lymphoma from three pediatric cancer centers. Errors were identified by chart review, in-home medication review, observation of administration, and interviews. Physician reviewers confirmed error (Fleiss' κ = 0.95), harm (Fleiss' κ = 0.82), and suggested interventions. Generalized linear mixed models with random effects were used to account for clustering by site. RESULTS: Among 131 children taking 1669 medications with 367 home visits, 408 errors were identified, including 242 with potential for harm and 39 with harm (1.0 harm per 1000 patient-days [95% CI, 0.1-9.8]). Ten percent of children were injured by errors and 42% had errors with potential for harm. Twenty-six percent of caregivers reported that miscommunication led to missed doses or overdoses at home. Children on >13 medications had significantly more serious medication errors than those on fewer medications (77% vs 61%; p = .05). Physician reviewers judged that improved communication among caregivers and between caregivers and clinicians may have prevented the most harm (66%). CONCLUSIONS: In this longitudinal study, 10% children with leukemia or lymphoma experienced adverse drug events because of outpatient medication errors. Improvements addressing communication with and among caregivers should be codeveloped with families and based on human-factors engineering. PLAIN LANGUAGE SUMMARY: In this longitudinal study, medication errors in the clinic, pharmacy, or at home among children with leukemia or lymphoma over a 7-month period were common, and 10% suffered harm because of errors. Children on >13 medications had significantly more serious medication errors than those on fewer medications (77% vs 61%; p = .05). Physician reviewers judged that improved communication among caregivers and between caregivers and clinicians may have prevented the most harm (66%). Improvements addressing communication with and among caregivers should be codeveloped with families and based on human-factors engineering.

A Chromosome-level assembly of the Japanese eel genome, insights into gene duplication and chromosomal reorganization.

Japanese eels (Anguilla japonica) are commercially important species, harvested extensively for food. Currently, this and related species (American and European eels) are challenging to breed on a commercial basis. As a result, the wild stock is used for aquaculture. Moreover, climate change, habitat loss, water pollution, and altered ocean currents affect eel populations negatively. Accordingly, the International Union for Conservation of Nature lists Japanese eels as endangered and on its red list. Here we presented a high-quality genome assembly for Japanese eels and demonstrated that large chromosome reorganizations occurred in the events of third-round whole-genome duplications (3R-WRDs). Several chromosomal fusions and fissions have reduced the ancestral protochromosomal number of 25 to 19 in the Anguilla lineage. A phylogenetic analysis of the expanded gene families showed that the olfactory receptors (group δ and ζ genes) and voltage-gated Ca2+ channels expanded significantly. Both gene families are crucial for olfaction and neurophysiology. Additional tandem and proximal duplications occurred following 3R-WGD to acquire immune-related genes for an adaptive advantage against various pathogens. The Japanese eel assembly presented here can be used to study other Anguilla species relating to evolution and conservation.

Experiences of community-dwelling older adults with chronic low back pain in Hong Kong and Switzerland - A qualitative study.

Introduction: The prevalence of chronic low back pain (LBP) increases with age and older adults are more vulnerable to develop chronic LBP. A recent Swiss study has shown that 78% of community-dwelling older adults aged ≥65 years experienced chronic LBP. Similarly, a study in Hong Kong found that approximately 30% of people aged above 60 years experienced chronic LBP. The aim of this collaborative research project was to illuminate older adults' experiences of living with chronic LBP and its implication on older adults' daily life in Western and Eastern cultures. Methods: Twenty-five older people experiencing chronic LBP living in Switzerland or Hong Kong were recruited through health professionals or community centres. Using semi-structured interviews, participants shared their experiences regarding chronic LBP and its implications on their daily life. The interviews were recorded and transcribed "ad verbatim" in the original language. An inductive thematic analysis was used, using a qualitative data analysis software program (NVivo) and a shared code book in English. The Swiss and Hong Kong research teams engaged in collaborative analysis until a consensus was established, taking into consideration of cultural specificities. Ethical approval was obtained from the local ethic committees in both regions. Results: Themes were related to negative perceptions/experiences: (1) interferences of daily function; (2) pessimistic attitudes toward their conditions/prognosis; and (3) self-perceived burden related to families. Conversely, four themes revealed attributes to social roles: (1) maintaining their roles in families; (2) experiencing supports from family and friends; (3) being content despite LBP; and (4) enjoying social activities. Cultural differences between Switzerland and Hong Kong were related to social circles and offers from the healthcare system, influencing individual experiences and perceptions. Discussion: Although chronic LBP may negatively impact older adults, individual approaches as well as social and health system supports influence older adults' attitude toward their pain and self-management strategies. Developing effective and culturally sensitive interventions for an elderly population with chronic LBP can be challenging but essential for the development of innovative healthcare services tailored to the population's needs. The methodological approach used for this research project establishes the framework for developing and evaluating complex interventions.

Hepatic metabolism gene expression and gut microbes in offspring, subjected to in-utero PFOS exposure and postnatal diet challenges.

We examined the changes in hepatic metabolic gene expression and gut microbiota of offspring exposed to PFOS in-utero. At GD17.5, our data showed that PFOS exposure decreased fetal bodyweights and hepatic metabolic gene expressions but increased relative liver mass and lipid accumulation. At PND21, in-utero high-dose PFOS-exposed offspring exhibited significantly greater bodyweight (catch-up-growth), associated with significant induction of hepatic metabolic gene expression. In addition, 16SrRNA-sequencing of the cecal samples revealed an increase in carbohydrate catabolism but a reduction in microbial polysaccharide synthesis and short-chain fatty acid (SCFA) metabolism. From PND21-80, a postnatal diet-challenge for the offspring was conducted. At PND80 under a normal diet, in-utero high-dose PFOS-exposed offspring maintained the growth "catch-up" effect. In contrast, in a high-fat-diet, the bodyweight of in-utero high-dose PFOS-exposed adult offspring were significantly lesser than the corresponding low-dose and control groups. Even though in the high-fat-diet, the in-utero PFOS-exposed adult offspring showed significant upregulation of hepatic metabolic genes, the lower bodyweight suggests that they had difficulty utilizing high-fat nutrients. Noteworthy, the metagenomic data showed a significant reduction in the biosynthesis of microbial polysaccharides, vitamin B, and SCFAs in the PFOS-exposed adult offspring. Furthermore, the observed effects were significantly reduced in the PFOS-exposed adult offspring with the high-fat diet but supplemented with sucrose. Our study demonstrated that in-utero PFOS exposure caused inefficient fat metabolism and increased the risk of hepatic steatosis in offspring.

Influence of cholesterol level on long-term survival and cardiac events after surgical coronary revascularization.

Objective: Statins have been shown to delay the inevitable progression of atherosclerosis in native coronaries and saphenous vein grafts, thereby reducing ischemic events after surgical coronary revascularization. However, there is significant controversy as to whether titrating statin therapy to concrete cholesterol targets is appropriate. Methods: A single-center retrospective analysis of 309 consecutive patients who underwent isolated coronary artery bypass graft in 2007 and 2008 was performed. Measurements of lipid profile subcomponents, namely total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides, in mmol/L, were obtained by retrospective review of electronic health records. The primary end point was cardiac death. The secondary end point was the composite of cardiac events, including cardiac death, nonfatal myocardial infarction, hospitalization for unstable angina, and target lesion revascularization. Database lock date was August 15, 2020. Results: The median follow-up duration was 12.5 years. Cardiac death occurred in 6.8% of the cohort. Cardiac events occurred in 21.7% of the cohort. New-onset myocardial infarction occurred in 8.7% (n = 27), of which 48.1% (n = 13) underwent repeat revascularization. A 2-level nested Cox proportional hazards regression model was constructed to determine whether cholesterol target attainment was independently associated with cardiac events. After risk adjustment, LDL-C, non-HDL-C, total cholesterol (TC), and TC/HDL-C ratio were independently associated with cardiac death. In receiver operating characteristics analyses, the optimal cut-off values for non-HDL-C, LDL-C, and TC/HDL-C ratio were 3.2 mmol/L, 2.3 mmol/L, and 3.5, respectively. Conclusions: Exposure to elevated LDL-C and non-HDL-C cholesterol levels independently predicted long-term cardiac death after coronary artery bypass graft.

LPS-Induced Systemic Inflammation Caused mPOA-FSH/LH Disturbance and Impaired Testicular Function.

Male reproductive function is key to the continuation of species and is under sophisticated regulation, challenged by various stressors including inflammation. In the lipopolysaccharide (LPS) intraperitoneal injection-induced acute systemic inflammation, male fecundity was compromised with decreased testosterone level, damaged spermatogenesis, and downregulations of testicular gene expression levels involved in steroidogenesis regulation and blood-testis barrier. It is also noteworthy that the testis is more sensitive to acute stress caused by LPS-induced systemic inflammation. LPS treatment resulted in lower testicular gene expression levels of steroidogenic acute regulatory protein, cholesterol side-chain cleavage enzyme, and cytochrome P450 family 11 subfamily B member 1 after LPS treatment, while no such decrease was found in the adrenal gland. In parallel to the significant decreases in testicular intercellular adhesion molecule 1, tight junction protein 1, and gap junction alpha-1 protein gene expression with LPS treatment, no decrease was found in the epididymis. In the brain, LPS treatment caused higher medial preoptic area (mPOA) activation in the hypothalamus, which is accompanied by elevated blood follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, suggesting a disturbed hypothalamic-pituitary-gonad axis function. Besides mPOA, brain c-fos mapping and quantitative analysis demonstrated a broad activation of brain nuclei by LPS, including the anterior cingulate cortex, lateral septum, paraventricular nucleus of the hypothalamus, basolateral amygdala, ventral tegmental area, lateral habenular nucleus, locus coeruleus, Barrington's nucleus, and the nucleus of the solitary tract, accompanied by abnormal animal behavior. Our data showed that LPS-induced inflammation caused not only local testicular damage but also a systemic disturbance at the brain-testis axis level.