Cancer control collaborations between China and African countries.

Over the past decade, China has emerged as Africa's largest trade partner and source of foreign direct investment, with public health ranked as a top priority in China-Africa collaborations. During the same period, cancer has emerged as a leading cause of death in Africa, with more than 700 000 deaths per year and projections of more than 1 million deaths per year by 2030. In this Review, we explore the effects of increasing China-Africa collaborations on cancer control in Africa. We review the published literature on health-care assistance, research, education and training, and infrastructure and present the results of an institutional review board-approved survey of African oncology health-care professionals and institutional leaders that assessed their perception of the effects of China-Africa collaborations. From peer-reviewed articles and grey literature, we found that the number of China-Africa collaborations have grown substantially over the past decade in different areas, especially in patient care and infrastructure. Research publications have also surged in quantity in the past decade compared with previous years. However, the survey results suggest research collaborations remain infrequent and that medical professionals in African cancer centres rarely participate in direct research collaborations with Chinese institutions. The Review also highlights the challenges and benefits of increasing China-Africa collaborations. Challenges include insufficient monitoring and evaluation of the projects in Africa and poor coordination and alignment of the various initiatives. The benefits of these collaborations for Africa include improved health outcomes, strengthened health systems, and socioeconomic development. Benefits are also apparent for China, such as securing energy and resource supplies, expanded trade and investment opportunities, and improved diplomatic relations. Overall, China-Africa collaborations are increasing and having a substantial effect in both China and the African continent. Recommendations to minimise the challenges and maximise the benefits for more positive consequences on cancer control in Africa are discussed.

Global Microbiota-Dependent Histone Acetylation Patterns Are Irreversible and Independent of Short Chain Fatty Acids.

BACKGROUND AND AIMS: Although germ-free mice are an indispensable tool in studying the gut microbiome and its effects on host physiology, they are phenotypically different than their conventional counterparts. While antibiotic-mediated microbiota depletion in conventional mice leads to physiologic alterations that often mimic the germ-free state, the degree to which the effects of microbial colonization on the host are reversible is unclear. The gut microbiota produce abundant short chain fatty acids (SCFAs), and previous studies have demonstrated a link between microbial-derived SCFAs and global hepatic histone acetylation in germ-free mice. APPROACH AND RESULTS: We demonstrate that global hepatic histone acetylation states measured by mass spectrometry remained largely unchanged despite loss of luminal and portal vein SCFAs after antibiotic-mediated microbiota depletion. In contrast to stable hepatic histone acetylation states, we see robust hepatic transcriptomic alterations after microbiota depletion. Additionally, neither dietary supplementation with supraphysiologic levels of SCFA nor the induction of hepatocyte proliferation in the absence of microbiota-derived SCFAs led to alterations in global hepatic histone acetylation. CONCLUSIONS: These results suggest that microbiota-dependent landscaping of the hepatic epigenome through global histone acetylation is static in nature, while the hepatic transcriptome is responsive to alterations in the gut microbiota.

Do the 2018 Leapfrog Group Minimal Hospital and Surgeon Volume Thresholds for Esophagectomy Favor Specific Patient Demographics?

OBJECTIVE: We examine how esophagectomy volume thresholds reflect outcomes relative to patient characteristics. SUMMARY BACKGROUND DATA: Esophagectomy outcomes are associated with surgeon and hospital operative volumes, leading the Leapfrog Group to recommend minimum annual volume thresholds of 7 and 20 respectively. METHODS: Patients undergoing esophagectomy for cancer were identified from the 2007-2013 New York and Florida Healthcare Cost and Utilization Project's State Inpatient Databases. Logit models adjusted for patient characteristics evaluated in-hospital mortality, complications, and prolonged length of stay (PLOS). Median surgeon and hospital volumes were compared between young-healthy (age 18-57, Elixhauser Comorbidity Index [ECI] <2) and older-sick patients (age ≥71, ECI >4). RESULTS: Of 4330 esophagectomy patients, 3515 (81%) were male, median age was 64 (interquartile range 58-71), and mortality was 4.0%. Patients treated by both low-volume surgeons and hospitals had the greatest mortality risk (5.0%), except in the case of older-sick patients mortality was highest at high-volume hospitals with high-volume surgeons (12%). For mortality <1%, annual hospital and surgeon volumes needed were 23 and 8, respectively; mortality rose to 4.2% when volumes dropped to the Leapfrog thresholds of 20 and 7, respectively. Complication rose from 53% to 63% when hospital and surgeon volumes decreased from 28 and 10 to 19 and 7, respectively. PLOS rose from 19% to 27% when annual hospital and surgeon volumes decreased from 27 and 8 to 20 and 7, respectively. CONCLUSIONS: Current Leapfrog Group esophagectomy volume guidelines may not predict optimal outcomes for all patients, especially at extremes of age and comorbidities.

The impact of COVID-19 pandemic on the health-seeking behaviour of an Asian population with acute respiratory infections in a densely populated community.

BACKGROUND: The COVID-19 pandemic led to the implementation of various non-pharmaceutical interventions (NPI) as the Singapore government escalated containment efforts from DORSCON Orange to Circuit Breaker. NPI include mandatory mask wearing, hand hygiene, social distancing, and closure of schools and workplaces. Considering the similar mode of transmission of COVID-19 and other pathogens related to acute respiratory infections (ARI), the effects of NPI could possibly lead to decreased ARI attendances in the community. This study aims to determine the year-on-year and weekly changes of ARI attendances across a cluster of polyclinics following the implementation of NPI. METHODS: The effect of the nation-wide measures on the health-seeking behaviour of the study population was examined over three periods: (1) 9 weeks prior to the start of Circuit Breaker (DORSCON Orange period), (2) 8 weeks during the Circuit Breaker, and (3) 9 weeks after easing of Circuit Breaker. Data on ARI attendances for the corresponding periods in 2019 were also extracted for comparison and to assess the seasonal variations of ARI. The average weekly workday ARI attendances were compared with those of the preceding week using Wilcoxon signed rank test. RESULTS: ARI attendances dropped steadily throughout the study period and were 50-80% lower than in 2019 since Circuit Breaker. They remained low even after Circuit Breaker ended. Positivity rate for influenza-like illnesses samples in the community was 0.0% from the last week of Circuit Breaker to end of study period. CONCLUSIONS: NPI and public education measures during DORSCON Orange and Circuit Breaker periods appear to be associated with the health-seeking behaviour of the public. Changing levels of perceived susceptibility, severity, benefits and barriers, and widespread visual cues based on the Health Belief Model may account for this change. Understanding the impact of NPI and shifts in the public's health-seeking behaviour will be relevant and helpful in the planning of future pandemic responses.

Repurposing Clinical Decision Support System Data to Measure Dosing Errors and Clinician-Level Quality of Care.

We aimed to develop and validate an instrument to detect hospital medication prescribing errors using repurposed clinical decision support system data. Despite significant efforts to eliminate medication prescribing errors, these events remain common in hospitals. Data from clinical decision support systems have not been used to identify prescribing errors as an instrument for physician-level performance. We evaluated medication order alerts generated by a knowledge-based electronic prescribing system occurring in one large academic medical center's acute care facilities for patient encounters between 2009 and 2012. We developed and validated an instrument to detect medication prescribing errors through a clinical expert panel consensus process to assess physician quality of care. Six medication prescribing alert categories were evaluated for inclusion, one of which - dose - was included in the algorithm to detect prescribing errors. The instrument was 93% sensitive (recall), 51% specific, 40% precise, 62% accurate, with an F1 score of 55%, positive predictive value of 96%, and a negative predictive value of 32%. Using repurposed electronic prescribing system data, dose alert overrides can be used to systematically detect medication prescribing errors occurring in an inpatient setting with high sensitivity.

FXR-Dependent Modulation of the Human Small Intestinal Microbiome by the Bile Acid Derivative Obeticholic Acid.

BACKGROUND & AIMS: Intestinal bacteria can modify the composition of bile acids and bile acids, which are regulated by the farnesoid X receptor, affect the survival and growth of gut bacteria. We studied the effects of obeticholic acid (OCA), a bile acid analogue and farnesoid X receptor agonist, on the intestinal microbiomes of humans and mice. METHODS: We performed a phase I study in 24 healthy volunteers given OCA (5, 10, or 25 mg/d for 17 days). Fecal and plasma specimens were collected at baseline (day 0) and on days 17 (end of dosing) and 37 (end of study). The fecal specimens were analyzed by shotgun meta-genomic sequencing. A Uniref90 high-stringency genomic analysis was used to assign specific genes to the taxonomic signature of bacteria whose abundance was associated with OCA. Male C57BL/6 mice were gavage fed daily with water, vehicle, or OCA (10 mg/kg) for 2 weeks. Small intestine luminal contents were collected by flushing with saline and fecal pellets were collected at baseline and day 14. Mouse samples were analyzed by 16S-tagged sequencing. Culture experiments were performed to determine the taxonomic-specific effects of bile acids and OCA on bacterial growth. RESULTS: Suppression of endogenous bile acid synthesis by OCA in subjects led to a reversible induction of gram-positive bacteria that are found in the small intestine and are components of the diet and oral microbiota. We found that bile acids decreased proliferation of these bacteria in minimum inhibitory concentration assays. In these organisms, there was an increase in the representation of microbial genomic pathways involved in DNA synthesis and amino acid metabolism with OCA treatment of subjects. Consistent with these findings, mice fed OCA had lower endogenous bile acid levels and an increased proportion of Firmicutes, specifically in the small intestine, compared with mice fed water or vehicle. CONCLUSIONS: In studying the effects of OCA in humans and mice, we found evidence for interactions between bile acids and features of the small intestinal microbiome. These findings indicate that farnesoid X receptor activation alters the intestinal microbiota and could provide opportunities for microbiome biomarker discovery or new approaches to engineering the human microbiome. ClinicalTrials.gov, NCT01933503.

Microbiota and the liver.

The gut microbiome outnumbers the human genome by 150-fold and plays important roles in metabolism, immune system education, tolerance development, and prevention of pathogen colonization. Dysbiosis has been associated with nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and alcoholic liver disease (ALD) as well as cirrhosis and complications. This article provides an overview of this relationship. Liver Transplantation 24 539-550 2018 AASLD.

Altered ubiquitin causes perturbed calcium homeostasis, hyperactivation of calpain, dysregulated differentiation, and cataract.

Although the ocular lens shares many features with other tissues, it is unique in that it retains its cells throughout life, making it ideal for studies of differentiation/development. Precipitation of proteins results in lens opacification, or cataract, the major blinding disease. Lysines on ubiquitin (Ub) determine fates of Ub-protein substrates. Information regarding ubiquitin proteasome systems (UPSs), specifically of K6 in ubiquitin, is undeveloped. We expressed in the lens a mutant Ub containing a K6W substitution (K6W-Ub). Protein profiles of lenses that express wild-type ubiquitin (WT-Ub) or K6W-Ub differ by only ∼2%. Despite these quantitatively minor differences, in K6W-Ub lenses and multiple model systems we observed a fourfold Ca(2+) elevation and hyperactivation of calpain in the core of the lens, as well as calpain-associated fragmentation of critical lens proteins including Filensin, Fodrin, Vimentin, ß-Crystallin, Caprin family member 2, and tudor domain containing 7. Truncations can be cataractogenic. Additionally, we observed accumulation of gap junction Connexin43, and diminished Connexin46 levels in vivo and in vitro. These findings suggest that mutation of Ub K6 alters UPS function, perturbs gap junction function, resulting in Ca(2+) elevation, hyperactivation of calpain, and associated cleavage of substrates, culminating in developmental defects and a cataractous lens. The data show previously unidentified connections between UPS and calpain-based degradative systems and advance our understanding of roles for Ub K6 in eye development. They also inform about new approaches to delay cataract and other protein precipitation diseases.

Early-onset stroke and vasculopathy associated with mutations in ADA2.

BACKGROUND: We observed a syndrome of intermittent fevers, early-onset lacunar strokes and other neurovascular manifestations, livedoid rash, hepatosplenomegaly, and systemic vasculopathy in three unrelated patients. We suspected a genetic cause because the disorder presented in early childhood. METHODS: We performed whole-exome sequencing in the initial three patients and their unaffected parents and candidate-gene sequencing in three patients with a similar phenotype, as well as two young siblings with polyarteritis nodosa and one patient with small-vessel vasculitis. Enzyme assays, immunoblotting, immunohistochemical testing, flow cytometry, and cytokine profiling were performed on samples from the patients. To study protein function, we used morpholino-mediated knockdowns in zebrafish and short hairpin RNA knockdowns in U937 cells cultured with human dermal endothelial cells. RESULTS: All nine patients carried recessively inherited mutations in CECR1 (cat eye syndrome chromosome region, candidate 1), encoding adenosine deaminase 2 (ADA2), that were predicted to be deleterious; these mutations were rare or absent in healthy controls. Six patients were compound heterozygous for eight CECR1 mutations, whereas the three patients with polyarteritis nodosa or small-vessel vasculitis were homozygous for the p.Gly47Arg mutation. Patients had a marked reduction in the levels of ADA2 and ADA2-specific enzyme activity in the blood. Skin, liver, and brain biopsies revealed vasculopathic changes characterized by compromised endothelial integrity, endothelial cellular activation, and inflammation. Knockdown of a zebrafish ADA2 homologue caused intracranial hemorrhages and neutropenia - phenotypes that were prevented by coinjection with nonmutated (but not with mutated) human CECR1. Monocytes from patients induced damage in cocultured endothelial-cell layers. CONCLUSIONS: Loss-of-function mutations in CECR1 were associated with a spectrum of vascular and inflammatory phenotypes, ranging from early-onset recurrent stroke to systemic vasculopathy or vasculitis. (Funded by the National Institutes of Health Intramural Research Programs and others.).

Comparing patient outcomes of academician-preceptors, hospitalist-preceptors, and hospitalists on internal medicine services in an academic medical center.

BACKGROUND: Patient outcomes with hospitalist care have been studied in many settings, yet little is known about how hospitalist care interacts with trainee care to affect patient outcomes in teaching hospitals. OBJECTIVES: The aim of this study was to compare patient outcomes between hospitalist-preceptors and hospitalists working alone (isolating the effect of housestaff involvement), and between hospitalist-preceptors and academician-preceptors (isolating the effect of attending type, given housestaff involvement). DESIGN: A four-year retrospective cohort study of patients (n = 13,313) admitted to all internal medicine services at an academic medical center from July 2008 to June 2012. MAIN MEASURES: Using generalized estimating equations, we measured readmission within 30 days, hospital length of stay, cost of the index hospitalization, and cumulative cost including readmissions within 30 days. KEY RESULTS: In the adjusted models, 30-day readmission odds were higher for academic-preceptors (OR, 1.14 [95% CI, 1.03 - 1.26]) and hospitalist-preceptors (OR, 1.10 [95% CI, 1.002 - 1.21]) than for hospitalists working alone. Compared with hospitalists working alone, academic-preceptors were associated with shorter length of stay (mean difference, 0.27 days [95% CI, 0.18 - 0.38]), lower index hospitalization costs (mean difference, $386 [95% CI, $192 - $576]), but similar cumulative inpatient costs within 30 days of discharge. Compared with hospitalists working alone, hospitalist-preceptors were associated with shorter length of stay (mean difference, 0.34 days [95% CI, 0.26 - 0.42]), lower index hospitalization cost (mean difference, $570 [95% CI, $378 - $760]), and a trend toward lower cumulative cost (mean difference, $1347 [95% CI, $254 - $2,816]). CONCLUSIONS: Preceptor-led medicine services were associated with more readmissions within 30 days, shorter lengths of stay, and lower index admission-associated costs. However, when considering cumulative hospitalization costs, patients discharged by academician-preceptors incurred the highest cost and hospitalist-preceptors incurred the lowest cost.

Systematic review and meta-analysis on outcomes for endoscopic versus external dacryocystorhinostomy.

BACKGROUND: Dacryocystorhinostomy (DCR) is commonly performed for epiphora, dacryocystitis and during tumor surgery. External (EXT-DCR) and endoscopic DCR (END-DCR) are both practiced. END-DCR was initially performed with laser (EL-DCR) but has shifted to careful bone removal with mechanical drills (EM-DCR). High level evidence from comparative cohorts was sought to compare outcomes. METHOD: Medline (1966 - January 28th, 2013) and Embase (1980 - January 28(th), 2013) were searched for comparative studies (RCT/cohorts) of END-DCR to EXT-DCR for acquired nasolacrimal duct (NLD) obstruction. Primary outcome was DCR success, defined as resolution of symptoms and/or patent NLD on irrigation or dacroscintography. Secondary outcomes were scarring, infection and post-operative bleeding. Meta-analysis was performed with the Mantel-Haenszel Method and presented as Risk Ratios (RR) with Confidence Intervals (CI). RESULTS: The search identified 3582 studies and 355 were reviewed after screening. Full text review yielded 19 studies (4 RCTs and 15 cohorts). Overall, EXT-DCR had slightly better success rates than END-DCR (RR 0.96, CI 0.93-1.00). However, EM-DCR outcomes were comparable to EXT-DCR (RR 1.02, CI 0.98-1.06), whereas EL-DCR had poorer outcomes (RR 0.85, CI 0.79-0.91) when compared separately. The RR for scarring, bleeding and infection with END-DCR versus EXT-DCR was 0.07 (CI 0.02-0.22), 0.72 (CI 0.46-1.13) and 0.24 (CI 0.11- 0.54), respectively. The rates of reported revision surgery were similar. CONCLUSION: DCR is a procedure with high success rates. Endoscopic procedures differ greatly by technique with EM-DCR offering comparable results to EXT-DCR, without the risk of cosmetically unacceptable scars.

A scoping review of empathy recognition in text using natural language processing.

OBJECTIVE: To provide a scoping review of studies on empathy recognition in text using natural language processing (NLP) that can inform an approach to identifying physician empathic communication over patient portal messages. MATERIALS AND METHODS: We searched 6 databases to identify relevant studies published through May 1, 2023. The study selection was conducted through a title screening, an abstract review, and a full-text review. Our process followed the PRISMA-ScR guidelines. RESULTS: Of the 2446 publications identified from our searches, 39 studies were selected for the final review, which summarized: (1) definitions and context of empathy, (2) data sources and tested models, and (3) model performance. Definitions of empathy varied in their specificity to the context and setting of the study. The most common settings in which empathy was studied were reactions to news stories, health-related social media forums, and counseling sessions. We also observed an expected shift in methods used that coincided with the introduction of transformer-based models. DISCUSSION: Aspects of the current approaches taken across various domains may be translatable to communication over a patient portal. However, the specific barriers to identifying empathic communication in this context are unclear. While modern NLP methods appear to be able to handle empathy-related tasks, challenges remain in precisely defining and measuring empathy in text. CONCLUSION: Existing work that has attempted to measure empathy in text using NLP provides a useful basis for future studies of patient-physician asynchronous communication, but consideration for the conceptualization of empathy is needed.

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.

Performance of a multigene genomic classifier and clinical parameters in predicting malignancy in a Southeast Asian cohort of patients with cytologically indeterminate thyroid nodules.

BACKGROUND: Most thyroid nodules are benign. It is important to determine the likelihood of malignancy in such nodules to avoid unnecessary surgery. The primary objective of this study was to characterize the genetic landscape and the performance of a multigene genomic classifier in fine-needle aspiration (FNA) biopsies of cytologically indeterminate thyroid nodules in a Southeast Asian cohort. The secondary objective was to assess the predictive contribution of clinical characteristics to thyroid malignancy. METHODS: This prospective, multicenter, blinded study included 132 patients with 134 nodules. Molecular testing (MT) with ThyroSeq v3 was performed on clinical or ex-vivo FNA samples. Centralized pathology review also was performed. RESULTS: Of 134 nodules, consisting of 61% Bethesda category III, 20% category IV, and 19% category V cytology, and 56% were histologically malignant. ThyroSeq yielded negative results in 37.3% of all FNA samples and in 42% of Bethesda category III-IV cytology nodules. Most positive samples had RAS-like (41.7%), followed by BRAF-like (22.6%), and high-risk (17.9%) alterations. Compared with North American patients, the authors observed a higher proportion of RAS-like mutations, specifically NRAS, in Bethesda categories III and IV and more BRAF-like mutations in Bethesda category III. The test had sensitivity, specificity, negative predictive value, and positive predictive value of 89.6%, 73.7%, 84.0%, and 82.1%, respectively. The risk of malignancy was predicted by positive MT and high-suspicion ultrasound characteristics according to American Thyroid Association criteria. CONCLUSIONS: Even in the current Southeast Asian cohort with nodules that had a high pretest cancer probability, MT could lead to potential avoidance of diagnostic surgery in 42% of patients with Bethesda category III-IV nodules. MT positivity was a stronger predictor of malignancy than clinical parameters.

Common dietary emulsifiers promote metabolic disorders and intestinal microbiota dysbiosis in mice.

Dietary emulsifiers are linked to various diseases. The recent discovery of the role of gut microbiota-host interactions on health and disease warrants the safety reassessment of dietary emulsifiers through the lens of gut microbiota. Lecithin, sucrose fatty acid esters, carboxymethylcellulose (CMC), and mono- and diglycerides (MDG) emulsifiers are common dietary emulsifiers with high exposure levels in the population. This study demonstrates that sucrose fatty acid esters and carboxymethylcellulose induce hyperglycemia and hyperinsulinemia in a mouse model. Lecithin, sucrose fatty acid esters, and CMC disrupt glucose homeostasis in the in vitro insulin-resistance model. MDG impairs circulating lipid and glucose metabolism. All emulsifiers change the intestinal microbiota diversity and induce gut microbiota dysbiosis. Lecithin, sucrose fatty acid esters, and CMC do not impact mucus-bacterial interactions, whereas MDG tends to cause bacterial encroachment into the inner mucus layer and enhance inflammation potential by raising circulating lipopolysaccharide. Our findings demonstrate the safety concerns associated with using dietary emulsifiers, suggesting that they could lead to metabolic syndromes.

Hot Instantaneous Temperature and Affect: Meaningful Activities as a Buffer for Older Adults With Low Socioeconomic Status.

Background and Objectives: Extremely hot temperature affects psychological well-being negatively, especially for older adults with lower socioeconomic status (SES). The objectives of this study are to examine: (a) the impact of hot instantaneous temperature on older adults' emotional well-being and (b) whether meaningful engagement could reduce the above impact, particularly for those of lower SES. Research Design and Methods: We conducted a quantitative time-sampling study during hot-weather months (May-September) in 2021 and 2022. The sample comprises 344 participants aged 60 years or older (Mage = 67.15, SDage = 5.26) living in urban areas of Hong Kong, where hot days (daily maximum temperature ≥33°C) accounted for 23% of the study days. Participants reported positive and negative affect, and engagement in meaningful activities, three times a day over a 10-day period, and wore sensors that tracked the instantaneous temperature of their immediate environment. Multilevel modeling was employed to examine the impacts on affect from temperature, SES, and meaningful activity engagement. Results: Hotter instantaneous temperature predicted greater momentary negative affect and less positive affect immediately afterwards. Meaningful engagement significantly buffered against the affective impacts of hotter temperature, and this buffering effect was more salient among older adults of lower SES. Discussion and implications: This study highlights the role of meaningful engagement in reducing the impact of hotter instantaneous temperature on older adults' emotional well-being, particularly for those of lower SES. Meaningful activity engagement may be capitalized on, as a strategy, to reduce climate-related social inequality.

The Fourth Age in Prospect.

OBJECTIVES: Higgs and Gilleard (2015) have uniquely theorized the fourth age as a "social imaginary" of deep old age that blends notions of frailty, abjection, and the moral relations of care. This report evaluates the coherence and reach of the fourth-age imaginary among older adults in relative good health. METHODS: In a qualitative design and within samples at 5 sites (in Czechia, Germany, Hong Kong, Taiwan, and the United States), 138 adults aged 70+ and still living independently discussed what it would mean to be "not independent" in later life. Replies referenced other people in general, specific people, and one's own actual or potential experience. RESULTS: Pooled across sites, the views of our participants confirm the theorized features of the social imaginary. Participants spoke readily of gateway infirmities heralding frailty and of frailty's abjection; expressed dread and abhorrence of dependence, some saying that death would be preferable; and were anxious about nursing homes and about burdening others with an obligation to care for them. DISCUSSION: The bleak but formidable reputation of the fourth age impinges on those living in the third. The consonant expression of fourth-age features among older adults on 3 continents supports Gilleard and Higgs's claim that the fourth-age imaginary "contains a universal ontological quality" owing to human corporeality and the senescence to which it is subject. Fourth-age studies that document the lived experience of frailty and dependence have the potential to undermine the imaginary and furnish new narratives for facing the future.

Ginger essential oil and citral ameliorates atherosclerosis in ApoE-/- mice by modulating trimethylamine-N-oxide and gut microbiota.

Recently, the role of the gut microbiota in diseases, including cardiovascular disease (CVD), has gained considerable research attention. Trimethylamine-N-oxide (TMAO), which is formed during ʟ-carnitine metabolism, promotes the formation of atherosclerotic plaques, causing thrombosis. Here, we elucidated the anti-atherosclerotic effect and mechanism of ginger (Zingiber officinale Roscoe) essential oil (GEO) and its bioactive compound citral in Gubra Amylin NASH (GAN) diet with ʟ-carnitine-induced atherosclerosis female ApoE-/- mice. Treatment with GEO at both low and high doses and citral inhibited the formation of aortic atherosclerotic lesions, improved plasma lipid profile, reduced blood sugar, improved insulin resistance, decreased plasma TMAO levels, and inhibited plasma inflammatory cytokines, especially interleukin-1ß. Additionally, GEO and citral treatment modulated gut microbiota diversity and composition by increasing the abundance of beneficial microbes and decreasing the abundance of CVD-related microbes. Overall, these results showed that GEO and citral may serve as potential dietary supplements for CVD prevention by improving gut microbiota dysbiosis.

The relationship between flow and bacteria in streams.

A method is proposed to relate the statistics of in-stream bacteria concentrations to the surface-runoff fraction of stream flow. The parameters of this relationship include the characteristic concentration of bacteria in surface runoff and the characteristic concentration of bacteria in the base flow, and these parameters can be derived from synoptic bacteria and flow measurements. The effectiveness of the proposed method is demonstrated at several U.S. locations for both Escherichia coli and fecal coliform bacteria. Application of the proposed method at a particular location showed that the method can be used to identify the most effective bacteria source controls and that conventional application of the load-duration curve might lead to erroneous identification of target sources.