Health Literacy, Individual and Community Engagement, and Cardiovascular Risks and Disparities: JACC: CardioOncology State-of-the-Art Review.

Cardiovascular and cancer outcomes intersect within the realm of cardio-oncology survivorship care, marked by disparities across ethnic, racial, social, and geographical landscapes. Although the clinical community is increasingly aware of this complex issue, effective solutions are trailing. To attain substantial public health impact, examinations of cancer types and cardiovascular risk mitigation require complementary approaches that elicit the patient's perspective, scale it to a population level, and focus on actionable population health interventions. Adopting such a multidisciplinary approach will deepen our understanding of patient awareness, motivation, health literacy, and community resources for addressing the unique challenges of cardio-oncology. Geospatial analysis aids in identifying key communities in need within both granular and broader contexts. In this review, we delineate a pathway that navigates barriers from individual to community levels. Data gleaned from these perspectives are critical in informing interventions that empower individuals within diverse communities and improve cardio-oncology survivorship.

A community health worker led diabetes self-management education program: Reducing patient and system burden.

AIMS: Conduct a secondary analysis of the TIME (Telehealth-supported, Integrated Community Health Workers (CHWs), Medication access, diabetes Education) made simple trial (SIMPLE) to evaluate healthcare utilization and explore variables that may have influenced HbA1c. METHODS: Participants (N = 134 [67/group]) were low-income, uninsured Hispanics with or at risk for type 2 diabetes mellitus. We included in-person and telehealth clinician visits, other visits, missed visits, orders placed, and guideline-adherence (e.g., vaccinations, quarterly HbA1c for uncontrolled diabetes). Using multivariable models, we explored for associations between HbA1c changes and these measures. RESULTS: The control arm had higher missed visits rates (intervention: 45 %; control: 56 %; p = 0.007) and missed telehealth appointments (intervention: 10 %; control: 27.4 %; p = 0.04). The intervention group received more COVID vaccinations than the control (p = 0.005). Other health measures were non-significant between groups. Intervention individuals' HbA1c improved with more missed visits (-0.60 %; p < 0.01) and worsened with improved guideline-adherent HbA1c measurements (HbA1c: 1.2 %; p = 0.057). The control group had non-significant HbA1c associations. CONCLUSIONS: Findings suggest that the SIMPLE trial's improved HbA1c levels stemmed from a CHW-driven intervention and not additional healthcare contact. Exploratory outcomes resulted in seemingly counterintuitive HbA1c associations with missed visits and guideline-adherent measurements; these may suggest that an intervention that enhances communication provides support to reduce the amount of follow-up needed by participants without sacrificing clinical improvements.

Teen Perspectives on Suicides and Deaths in an Affluent Community: Perfectionism, Protection, and Exclusion.

Clusters of youth suicide and death are tragic for communities and present long-term consequences for the surviving youths. Despite an awareness of community-based patterns in youth suicide, our understanding of the social and community factors behind these events remains poor. While links between poverty and suicide have been well documented, wealthy communities are rarely targeted in suicide research. In response to this gap, we conducted ethnographic research in a wealthy U.S. town that, over a recent 10-year period, witnessed at least four youth suicides and seven more youth accidental deaths. Our interviews (n = 30) explored community values and stressors, interpersonal relationships, and high school experiences on participant perceptions of community deaths. Youth participants characterize their affluent community as having (1) perfectionist standards; (2) permissive and sometimes absent parents; (3) socially competitive and superficial relationships; and (4) a "bubble" that is protective but also exclusionary. Our qualitative findings reveal network influence in teen suicides and accidental deaths in a wealthy community. Greater attention paid to the negative effects of subcultural values and stressors in affluent communities is warranted. Further, our work promotes the value of ethnographic, community-based methodologies for suicidology and treatment.

Worldwide population prevalence and impact of sub-diagnostic gastrointestinal symptoms.

BACKGROUND: The Rome Foundation Global Epidemiology Study (RFGES) found that 40.3% of adults in 26 internet-surveyed countries met Rome IV criteria for disorders of gut-brain interaction (DGBI). However, additional people not meeting DGBI criteria may also be burdened by frequent gastrointestinal symptoms. AIMS: To explore the prevalence and demographic distribution of sub-diagnostic gastrointestinal symptoms, and the hypothesised associated effects on quality of life (QoL), life functioning and healthcare needs. METHODS: We analysed data from the RFGES survey, which included the Rome IV diagnostic questionnaire and QoL, psychological, work productivity and healthcare questions. RESULTS: Of the 50,033 people without a history of organic gastrointestinal disorders, 25.3% classified in the sub-diagnostic group (no DGBI but one or more frequent gastrointestinal symptoms), 41.4% had DGBI and 33.4% had no frequent gastrointestinal symptoms (non-GI group). Sub-diagnostic prevalence in different world regions ranged from 22.2% (North America) to 30.5% (Middle East), was slightly higher among males than females and decreased with age. The sub-diagnostic group was intermediate between the non-GI and DGBI groups, and significantly different from both of them on QoL, anxiety, depression, somatisation, healthcare utilisation and life and work impairment. CONCLUSIONS: One in four adults without organic gastrointestinal disorders or DGBI report frequent gastrointestinal symptoms. This sub-diagnostic group has reduced QoL, greater psychological and non-GI bodily symptoms, impaired work productivity and life activities and greater healthcare use compared to non-GI individuals. This suggests that many in this sub-diagnostic group might benefit from healthcare services or symptom self-management advice.

Cost-Effectiveness of eRAPID eHealth Intervention for Symptom Management During Chemotherapy.

PURPOSE: A randomized controlled trial of online symptom monitoring during chemotherapy with electronic patient self-Reporting of Adverse-events: Patient Information and aDvice (eRAPID) system found improved symptom control and patient self-efficacy, without increasing hospital admissions and visits. The aim of this study was to evaluate the cost-effectiveness of the eRAPID eHealth intervention compared with usual care for patients receiving systemic treatment for colorectal, breast, or gynecologic cancers in the United Kingdom. METHODS: An embedded economic evaluation was conducted alongside the trial evaluating the effectiveness of eRAPID from health care provider and societal perspectives. Costs and quality-adjusted life-years (QALYs) of patients were compared over 18 weeks of the trial. Incremental cost-effectiveness ratios (ICERs) were estimated and compared with the National Institute for Health and Care Excellence cost-effectiveness threshold. Uncertainty around the ICER was explored using nonparametric bootstrapping and sensitivity analyses. Follow-up data were collected 12-months after random assignment for a subset of the study sample to conduct exploratory analysis of potential longer-term effects. RESULTS: Patients in the eRAPID group had the highest QALY gain and lowest costs over 18 weeks. Although differences were small and not statistically significant, eRAPID had a 55%-58% probability of being more cost-effective than usual care. Patient out-of-pocket costs were lower in the eRAPID group, indicating eRAPID may help patients access support needed within the National Health Service. Exploratory 12-months analysis showed small differences in costs and QALYs, with higher QALY gains in the eRAPID group but also higher costs. Exploratory subgroup analysis by disease status indicated that the eRAPID intervention was cost-effective for patients with early-stage cancers but not for patients with metastatic disease. CONCLUSION: Despite small differences in QALYs and costs, the analyses show potential cost-effectiveness of online symptom monitoring, when added to usual care, particularly during adjuvant systemic treatment for early-stage cancers.

Redesigning Recruitment and Engagement Strategies for Virtual Culinary Medicine and Medical Nutrition Interventions in a Randomized Trial of Patients with Uncontrolled Type 2 Diabetes.

In-person culinary medicine (CM) can improve health behaviors, but its translation to virtual platforms and impact on diabetes outcomes are not well described. We designed a pragmatic trial comparing the effectiveness of virtual CM (eCM) to Medical Nutrition Therapy on diabetes outcomes among patients with uncontrolled diabetes within a safety-net healthcare system. All participants were provided cooking equipment and food from a food pantry. Due to low initial eCM participation, recruitment was paused, and eight semi-structured interviews were conducted to solicit feedback on study appeal, operations, and barriers to participation. Rapid thematic analysis was used to modify study operations. We found that participants were interested in the study and motivated by health concerns. While they valued food distribution and cooking equipment, they highlighted transportation barriers and conflicts with the pick-up time/location. Some eCM participants expressed discomfort with the virtual platform or preferred to observe rather than cook along. Study operations were modified by (1) moving supply pick-up to a familiar community clinic and diversifying food pick-up locations; (2) offering an in-person orientation to the program to increase comfort with the virtual platform; (3) emphasizing the credibility and relatability of the eCM instructor and encouraging participation of family members. This redesign led to the recruitment of 79 participants, of whom 75% attended at least one class. In conclusion, participant feedback informed pragmatic changes in study operations that increased engagement in this ongoing trial and may inform future eCM program design.

Obesity exacerbates influenza-induced respiratory disease via the arachidonic acid-p38 MAPK pathway.

Obesity is a risk factor for severe influenza, and asthma exacerbations caused by respiratory viral infections. We investigated mechanisms that increase the severity of airway disease related to influenza in obesity using cells derived from obese and lean individuals, and in vitro and in vivo models. Primary human nasal epithelial cells (pHNECs) derived from obese compared with lean individuals developed increased inflammation and injury in response to influenza A virus (IAV). Obese mice infected with influenza developed increased airway inflammation, lung injury and elastance, but had a decreased interferon response, compared with lean mice. Lung arachidonic acid (AA) levels increased in obese mice infected with IAV; arachidonic acid increased inflammatory cytokines and injury markers in response to IAV in human bronchial epithelial (HBE) cells. Obesity in mice, and AA in HBE cells, increased activation of p38 MAPK signaling following IAV infection; inhibiting this pathway attenuated inflammation, injury and tissue elastance responses, and improved survival. In summary, obesity increases disease severity in response to influenza infection through activation of the p38 MAPK pathway in response to altered arachidonic acid signaling.

Diet-induced obesity worsens allergen-induced type 2/type 17 inflammation in airways by enhancing DUOX1 activation.

More than 50% of people with asthma in the United States are obese, and obesity often worsens symptoms of allergic asthma and impairs response to treatment. Based on previously established roles of the epithelial NADPH oxidase DUOX1 in allergic airway inflammation, we addressed the potential involvement of DUOX1 in altered allergic inflammation in the context of obesity. Intranasal house dust mite (HDM) allergen challenge of subjects with allergic asthma induced rapid secretion of IL-33, then IL-13, into the nasal lumen, responses that were significantly enhanced in obese asthmatic subjects (BMI >30). Induction of diet-induced obesity (DIO) in mice by high-fat diet (HFD) feeding similarly enhanced acute airway responses to intranasal HDM challenge, particularly with respect to secretion of IL-33 and type 2/type 3 cytokines, and this was associated with enhanced epithelial DUOX1 expression and was avoided in DUOX1-deficient mice. DIO also enhanced DUOX1-dependent features of chronic HDM-induced allergic inflammation. Although DUOX1 did not affect overall weight gain by HFD feeding, it contributed to glucose intolerance, suggesting a role in glucose metabolism. However, glucose intolerance induced by short-term HFD feeding, in the absence of adiposity, was not sufficient to alter HDM-induced acute airway responses. DIO was associated with enhanced presence of the adipokine leptin in the airways, and leptin enhanced DUOX1-dependent IL-13 and mucin production in airway epithelial cells. In conclusion, augmented inflammatory airway responses to HDM in obesity are associated with increases in airway epithelial DUOX1, and by increased airway epithelial leptin signaling.

Moral Distress Under Structural Violence: Clinician Experience in Brazil Caring for Low-Income Families of Children with Severe Disabilities.

Rigorous attention has been paid to moral distress among healthcare professionals, largely in high-income settings. More obscure is the presence and impact of moral distress in contexts of chronic poverty and structural violence. Intercultural ethics research and dialogue can help reveal how the long-term presence of morally distressing conditions might influence the moral experience and agency of healthcare providers. This article discusses mixed-methods research at one nongovernmental social support agency and clinic in Rio de Janeiro, Brazil. Chronic levels of moral distress and perceptions of moral harm among clinicians in this setting were both violent, following Nancy Scheper-Hughes' use of that term, and a source of exceptional and innovative care. Rather than glossing over the moral variables of work in such desperate extremes, ethnography in these settings reveals novel skills and strategies for managing moral distress.

Online Symptom Monitoring During Pelvic Radiation Therapy: Randomized Pilot Trial of the eRAPID Intervention.

PURPOSE: Radiation therapy (RT) and chemoRT for pelvic cancers increase survival but are associated with serious treatment-related symptoms. Electronic-patient self-Reporting of Adverse-events: Patient Information and aDvice (eRAPID) is a secure online system for patients to self-report symptoms, generating immediate advice for hospital contact or self-management. This pilot study aimed to establish feasibility and acceptability of the system. METHODS AND MATERIALS: In a prospective 2-center randomized parallel-group pilot study, patients undergoing radical pelvic RT for prostate cancer (prostateRT) or chemoRT for lower gastrointestinal and gynecological cancers were randomized to usual care (UC) or eRAPID (weekly online symptom reporting for 12, 18, and 24 weeks). Primary outcomes were recruitment/attrition, study completion, and patient adherence. Secondary outcomes were effect on hospital services and performance of patient outcome measures. Missing data, floor/ceiling effects, and mean change scores were examined for Functional Assessment of Cancer Therapy (FACT-G), European Organisation for Research and Treatment of Cancer, Quality of Life (EORTC QLQ C-30), self-efficacy, and EuroQol (EQ5D). RESULTS: From 228 patients approached, 167 (73.2%) were consented and randomized (83, eRAPID; 84, UC; 87, prostateRT; 80, chemoRT); 150 of 167 completed 24 study weeks. Only 16 patients (9.6%) withdrew (10, eRAPID; 6, UC). In the eRAPID arm, completion rates were higher in patients treated with prostateRT compared with chemoRT (week 1, 93% vs 69%; week 2, 93% vs 68%; week 12, 69% vs 55%). Overall, over 50% of online reports triggered self-management advice for milder adverse events. Unscheduled hospital contact was low, with no difference between eRAPID and UC. Return rates for outcome measures were excellent in prostateRT (97%-91%; 6-24 weeks) but lower in chemoRT (95%-55%; 6-24 weeks). Missing data were low (1%-4.1%), ceiling effects were evident in EQ5D-5L, self-efficacy-scale, and FACT-Physical Wellbeing. At 6 weeks, the chemoRT-eRAPID group showed less deterioration in FACT-G, EORTC QLQ-C30, and EQ5D-Visual Analogue Scale than UC, after baseline adjustment. CONCLUSIONS: eRAPID was successfully added to UC at 2 cancer centers in different patient populations. Acceptability and feasibility were confirmed with excellent adherence by prostate patients, but lower by those undergoing chemoRT for gynecological cancers.

Mitoquinone mesylate attenuates pathological features of lean and obese allergic asthma in mice.

Obesity is associated with severe, difficult-to-control asthma, and increased airway oxidative stress. Mitochondrial reactive oxygen species (mROS) are an important source of oxidative stress in asthma, leading us to hypothesize that targeting mROS in obese allergic asthma might be an effective treatment. Using a mouse model of house dust mite (HDM)-induced allergic airway disease in mice fed a low- (LFD) or high-fat diet (HFD), and the mitochondrial antioxidant MitoQuinone (MitoQ), we investigated the effects of obesity and ROS on HDM-induced airway inflammation, remodeling, and airway hyperresponsiveness (AHR). Obese allergic mice showed increased lung tissue eotaxin, airway tissue eosinophilia, and AHR compared with lean allergic mice. MitoQ reduced airway inflammation, remodeling, and hyperreactivity in both lean and obese allergic mice, and tissue eosinophilia in obese-allergic mice. Similar effects were observed with decyl triphosphonium (dTPP+), the hydrophobic cationic moiety of MitoQ lacking ubiquinone. HDM-induced oxidative sulfenylation of proteins was increased particularly in HFD mice. Although only MitoQ reduced sulfenylation of proteins involved in protein folding in the endoplasmic reticulum (ER), ER stress was attenuated by both MitoQ and dTPP+ suggesting the anti-allergic effects of MitoQ are mediated in part by effects of its hydrophobic dTPP+ moiety reducing ER stress. In summary, oxidative signaling is an important mediator of allergic airway disease. MitoQ, likely through reducing protein oxidation and affecting the UPR pathway, might be effective for the treatment of asthma and specific features of obese asthma.

Effect of a Patient Decision Aid on Preferences for Colorectal Cancer Screening Among Older Adults: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Guidelines recommend individualized decision-making for colorectal cancer (CRC) screening among adults aged 76 to 84 years, a process that includes a consideration of health state and patient preference. Objective: To determine whether a targeted patient decision aid would align older adults' screening preference with their potential to benefit from CRC screening. Design, Setting, and Participants: This is a prespecified secondary analysis from a randomized clinical trial. Participants aged 70 to 84 years who were not up to date with screening and had an appointment within 6 weeks were purposively sampled by health state (poor, intermediate, or good) at 14 community-based primary care practices and block randomized to receive the intervention or control. Patients were recruited from March 1, 2012, to February 28, 2015, and these secondary analyses were performed from January 15 to March 1, 2022. Interventions: Patient decision aid targeted to age and sex. Main Outcomes and Measures: The primary outcome of this analysis was patient preference for CRC screening. The a priori hypothesis was that the decision aid (intervention) group would reduce the proportion preferring screening among those in poor and intermediate health compared with the control group. Results: Among the 424 participants, the mean (SD) age was 76.8 (4.2) years; 248 (58.5%) of participants were women; and 333 (78.5%) were White. The proportion preferring screening in the intervention group was less than in the control group for those in the intermediate health state (34 of 76 [44.7%] vs 40 of 73 [54.8%]; absolute difference, -10.1% [95% CI, -26.0% to 5.9%]) and in the poor health state (24 of 62 [38.7%] vs 33 of 61 [54.1%]; absolute difference, -15.4% [95% CI, -32.8% to 2.0%]). These differences were not statistically significant. The proportion of those in good health who preferred screening was similar between the intervention and control groups (44 of 74 [59.5%] for intervention vs 46 of 75 [61.3%] for control; absolute difference, -1.9% [95% CI, -17.6% to 13.8%]). Conclusions and Relevance: The findings of this secondary analysis of a clinical trial did not demonstrate statistically significant differences in patient preferences between the health groups. Additional studies that are appropriately powered are needed to determine the effect of the decision aid on the preferences of older patients for CRC screening by health state. Trial Registration: ClinicalTrials.gov Identifier: NCT01575990.

Professional competition amidst intractable maternal mortality: Midwifery in rural Pakistan during the COVID-19 pandemic.

Low-income countries with intransigent maternal mortality rates often follow WHO guidelines that prioritize access to skilled, or professionalized, prenatal and birthing care. Yet the impact of these initiatives in areas still suffering high maternal mortality is opaque. Despite heavy and long investments, the professionalization of midwifery in Pakistan is incomplete, and declines in maternal mortality have plateaued. Traditional midwives have lost status, but they continue to see clients and have influence in their rural communities. We conducted a rapid ethnography among traditional midwives (Dais) and trained Lady Health Workers (LHWs) in two communities of Attock, Pakistan from May to July of 2020. Our findings underscore the importance of long-term presence and trust to maternal care, especially in conditions of resource scarcity or fear (e.g., fear of COVID). We provide evidence of overt disparagement of Dais by LHWs; (2) illustration of the conflicts between gender norms and biomedical priorities of hospitalized births; and (3) exacerbated fear of hospitals during COVID, which served to highlight the advantages of Dai care. Professionalization programs for midwifery must include structures and training to ensure collaborative communications across the country's midwives. Failure to respect the rational decisions of traditional midwives and their patients in circumstances of scarcity, high stress, and isolation only ignores the material and cultural conditions of these vulnerable communities.

Macrophage-intrinsic DUOX1 contributes to type 2 inflammation and mucus metaplasia during allergic airway disease.

The NADPH oxidase DUOX1 contributes to epithelial production of alarmins, including interleukin (IL)-33, in response to injurious triggers such as airborne protease allergens, and mediates development of mucus metaplasia and airway remodeling in chronic allergic airways diseases. DUOX1 is also expressed in non-epithelial lung cell types, including macrophages that play an important role in airway remodeling during chronic lung disease. We therefore conditionally deleted DUOX1 in either lung epithelial or monocyte/macrophage lineages to address its cell-specific actions in innate airway responses to acute airway challenge with house dust mite (HDM) allergen, and in chronic HDM-driven allergic airway inflammation. As expected, acute responses to airway challenge with HDM, as well as type 2 inflammation and related features of airway remodeling during chronic HDM-induced allergic inflammation, were largely driven by DUOX1 with the respiratory epithelium. However, in the context of chronic HDM-driven inflammation, DUOX1 deletion in macrophages also significantly impaired type 2 cytokine production and indices of mucus metaplasia. Further studies revealed a contribution of macrophage-intrinsic DUOX1 in macrophage recruitment upon chronic HDM challenge, as well as features of macrophage activation that impact on type 2 inflammation and remodeling.

Indigenous sovereignty, data sourcing, and knowledge sharing for health.

In this article, we consider the impacts of the COVID-19 pandemic on Indigenous Peoples (IPs) by reporting on information-gathering work across two non-governmental and Indigenous organisations to compensate where federal systems failed. Strategies IPs have employed to understand and respond to the pandemic, and described here, include: collaborative efforts across communities intra- and inter-nationally; open-source data platforms; and small-scale epidemiological research. Our review exposes the informational politics faced by Indigenous organisations and communities, and their struggle to pursue needed resources or protections while avoiding the critiques of 'post-neoliberal' and 'science denialism'. We conclude by suggesting ways that Indigenous communities improve our understanding of their needs during public health crises, and maintain both informational and medical self-governance.

Oxidation-Dependent Activation of Src Kinase Mediates Epithelial IL-33 Production and Signaling during Acute Airway Allergen Challenge.

The respiratory epithelium forms the first line of defense against inhaled pathogens and acts as an important source of innate cytokine responses to environmental insults. One critical mediator of these responses is the IL-1 family cytokine IL-33, which is rapidly secreted upon acute epithelial injury as an alarmin and induces type 2 immune responses. Our recent work highlighted the importance of the NADPH oxidase dual oxidase 1 (DUOX1) in acute airway epithelial IL-33 secretion by various airborne allergens associated with H2O2 production and reduction-oxidation-dependent activation of Src kinases and epidermal growth factor receptor (EGFR) signaling. In this study, we show that IL-33 secretion in response to acute airway challenge with house dust mite (HDM) allergen critically depends on the activation of Src by a DUOX1-dependent oxidative mechanism. Intriguingly, HDM-induced epithelial IL-33 secretion was dramatically attenuated by small interfering RNA- or Ab-based approaches to block IL-33 signaling through its receptor IL1RL1 (ST2), indicating that HDM-induced IL-33 secretion includes a positive feed-forward mechanism involving ST2-dependent IL-33 signaling. Moreover, activation of type 2 cytokine responses by direct airway IL-33 administration was associated with ST2-dependent activation of DUOX1-mediated H2O2 production and reduction-oxidation-based activation of Src and EGFR and was attenuated in Duox1 -/- and Src +/- mice, indicating that IL-33-induced epithelial signaling and subsequent airway responses involve DUOX1/Src-dependent pathways. Collectively, our findings suggest an intricate relationship between DUOX1, Src, and IL-33 signaling in the activation of innate type 2 immune responses to allergens, involving DUOX1-dependent epithelial Src/EGFR activation in initial IL-33 secretion and in subsequent IL-33 signaling through ST2 activation.

Vacuolar H+-ATPase and Na+/K+-ATPase energize Na+ uptake mechanisms in the nuchal organ of the hyperregulating freshwater crustacean Daphnia magna.

The nuchal organ of the embryos and neonates of the cladoceran, Daphnia magna, has been shown to be a site of Na+ influx and H+, NH4+ and Cl- efflux. This study combines the scanning ion-selective electrode technique with application of inhibitors of specific transporters to assess the mechanisms of Na+ transport across the nuchal organ. Na+ influx across the nuchal organ was inhibited both by inhibitors of the Na+/K+-ATPase (ouabain, bufalin) and by inhibitors of the vacuolar H+-ATPase (bafilomycin, N-ethylmaleimde, 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole, KM91104, S-nitrosoglutathione). Na+ influx was unaffected by the epithelial Na+ channel blocker benzamil, but was sensitive to ethylisopropyl amiloride and elevated external ammonium concentrations, consistent with roles for Na+/H+ and Na+/NH4+ exchangers in the apical membrane but not Na+ channels. Transport across the basolateral membrane into the haemolymph is proposed to involve the Na+/K+-ATPase and a thiazide-sensitive Na+/Cl- cotransporter.

The physiology of fish in acidic waters rich in dissolved organic carbon, with specific reference to the Amazon basin: Ionoregulation, acid-base regulation, ammonia excretion, and metal toxicity.

Although blackwaters, named for their rich content of dissolved organic carbon (DOC), are often very poor in ions and very acidic, they support great fish biodiversity. Indeed, about 8% of all freshwater fish species live in the blackwaters of the Rio Negro watershed in the Amazon basin. We review how native fish survive these harsh conditions that would kill most freshwater fish, with a particular focus on the role of DOC, a water quality parameter that has been relatively understudied. DOC, which is functionally defined by its ability to pass through a 0.45-µm filter, comprises a diverse range of compounds formed by the breakdown of organic matter and is quantified by its carbon component that is approximately 50% by mass. Adaptations of fish to acidic blackwaters include minimal acid-base disturbances associated with a unique, largely unknown, high-affinity Na+ uptake system that is resistant to inhibition by low pH in members of the Characiformes, and very tight regulation of Na+ efflux at low pH in the Cichliformes. Allochthonous (terrigenous) DOC, which predominates in blackwaters, consists of larger, more highly colored, reactive molecules than autochthonous DOC. The dissociation of protons from allochthonous components such as humic and fulvic acids is largely responsible for the acidity of these blackwaters, yet at the same time, these components may help protect organisms against the damaging effects of low water pH. DOC lowers the transepithelial potential (TEP), mitigates the inhibition of Na+ uptake and ammonia excretion, and protects against the elevation of diffusive Na+ loss in fish exposed to acidic waters. It also reduces the gill binding and toxicity of metals. At least in part, these actions reflect direct biological effects of DOC on the gills that are beneficial to ionoregulation. After chronic exposure to DOC, some of these protective effects persist even in the absence of DOC. Two characteristics of allochthonous DOC, the specific absorbance coefficient at 340 nm (determined optically) and the PBI (determined by titration), are indicative of both the biological effectiveness of DOC and the ability to protect against metal toxicity. Future research needs are highlighted, including a greater mechanistic understanding of the actions of DOCs on gill ionoregulatory function, morphology, TEP, and metal toxicity. These should be investigated in a wider range of native fish Orders that inhabit one of the world's greatest biodiversity hotspots for freshwater fishes.

Decolonizing Care at Diagnosis: Culture, History, and Family at an Urban Inter-tribal Clinic.

The decolonization framework in medical anthropology is slowly reframing tropes of cultural competency toward decolonizing health care. For decolonization of health care to occur, both colonial histories and continuing postcolonial inequities must be recognized from the first diagnostic moment. We report on qualitative research into the role of culture, history, and family experience in person-specific reactions to receipt of a diagnosis. A collaborative approach at an urban inter-tribal clinic was used to interview patients with a recent (within six months) diagnosis of diabetes or related condition. Interviews revealed ways that the Relocation Act eventuated in isolation, poverty, and diabetes among now-urban Native Americans. We discuss how patients may or may not have the ability to (re)connect with their heritage and may simultaneously perceive only recent family contexts as influential in their diabetes. We conclude by acknowledging how postcolonial harms are not captured in diagnoses but should not be left out of diagnostic discussions.