Widespread deoxygenation of temperate lakes.

The concentration of dissolved oxygen in aquatic systems helps to regulate biodiversity1,2, nutrient biogeochemistry3, greenhouse gas emissions4, and the quality of drinking water5. The long-term declines in dissolved oxygen concentrations in coastal and ocean waters have been linked to climate warming and human activity6,7, but little is known about the changes in dissolved oxygen concentrations in lakes. Although the solubility of dissolved oxygen decreases with increasing water temperatures, long-term lake trajectories are difficult to predict. Oxygen losses in warming lakes may be amplified by enhanced decomposition and stronger thermal stratification8,9 or oxygen may increase as a result of enhanced primary production10. Here we analyse a combined total of 45,148 dissolved oxygen and temperature profiles and calculate trends for 393 temperate lakes that span 1941 to 2017. We find that a decline in dissolved oxygen is widespread in surface and deep-water habitats. The decline in surface waters is primarily associated with reduced solubility under warmer water temperatures, although dissolved oxygen in surface waters increased in a subset of highly productive warming lakes, probably owing to increasing production of phytoplankton. By contrast, the decline in deep waters is associated with stronger thermal stratification and loss of water clarity, but not with changes in gas solubility. Our results suggest that climate change and declining water clarity have altered the physical and chemical environment of lakes. Declines in dissolved oxygen in freshwater are 2.75 to 9.3 times greater than observed in the world's oceans6,7 and could threaten essential lake ecosystem services2,3,5,11.

Performance of Urinalysis Parameters in Predicting Urinary Tract Infection: Does One Size Fit all?

In a multi-hospital cohort study of 3392 patients, positive urinalysis parameters had poor positive predictive value for diagnosing urinary tract infection (UTI). Combined urinalysis parameters (pyuria or nitrite) performed better than pyuria alone for ruling out UTI. However, performance of all urinalysis parameters was poor in older women.

Proposing the "Continuum of UTI" for a Nuanced Approach to Diagnosis and Management of Urinary Tract Infections.

PURPOSE: Patients with suspected UTIs are categorized into 3 clinical phenotypes based on current guidelines: no UTI, asymptomatic bacteriuria (ASB), or UTI. However, all patients may not fit neatly into these groups. Our objective was to characterize clinical presentations of patients who receive urine tests using the "continuum of UTI" approach. MATERIALS AND METHODS: This was a retrospective cohort study of a random sample of adult noncatheterized inpatient and emergency department encounters with paired urinalysis and urine cultures from 5 hospitals in 3 states between January 01, 2017, and December 31, 2019. Trained abstractors collected clinical (eg, symptom) and demographic data. A focus group discussion with multidisciplinary experts was conducted to define the continuum of UTI, a 5-level classification scheme that includes 2 new categories: lower urinary tract symptoms/other urologic symptoms and bacteriuria of unclear significance. The newly defined continuum of UTI categories were compared to the current UTI classification scheme. RESULTS: Of 220,531 encounters, 3392 randomly selected encounters were reviewed. Based on the current classification scheme, 32.1% (n = 704) had ASB and 53% (n = 1614) did not have a UTI. When applying the continuum of UTI categories, 68% of patients (n = 478) with ASB were reclassified as bacteriuria of unclear significance and 29% of patients (n = 467) with "no UTI" were reclassified to lower urinary tract symptoms/other urologic symptoms. CONCLUSIONS: Our data suggest the need to reframe our conceptual model of UTI vs ASB to reflect the full spectrum of clinical presentations, acknowledge the diagnostic uncertainty faced by frontline clinicians, and promote a nuanced approach to diagnosis and management of UTIs.

Anoxia begets anoxia: A positive feedback to the deoxygenation of temperate lakes.

Declining oxygen concentrations in the deep waters of lakes worldwide pose a pressing environmental and societal challenge. Existing theory suggests that low deep-water dissolved oxygen (DO) concentrations could trigger a positive feedback through which anoxia (i.e., very low DO) during a given summer begets increasingly severe occurrences of anoxia in following summers. Specifically, anoxic conditions can promote nutrient release from sediments, thereby stimulating phytoplankton growth, and subsequent phytoplankton decomposition can fuel heterotrophic respiration, resulting in increased spatial extent and duration of anoxia. However, while the individual relationships in this feedback are well established, to our knowledge, there has not been a systematic analysis within or across lakes that simultaneously demonstrates all of the mechanisms necessary to produce a positive feedback that reinforces anoxia. Here, we compiled data from 656 widespread temperate lakes and reservoirs to analyze the proposed anoxia begets anoxia feedback. Lakes in the dataset span a broad range of surface area (1-126,909 ha), maximum depth (6-370 m), and morphometry, with a median time-series duration of 30 years at each lake. Using linear mixed models, we found support for each of the positive feedback relationships between anoxia, phosphorus concentrations, chlorophyll a concentrations, and oxygen demand across the 656-lake dataset. Likewise, we found further support for these relationships by analyzing time-series data from individual lakes. Our results indicate that the strength of these feedback relationships may vary with lake-specific characteristics: For example, we found that surface phosphorus concentrations were more positively associated with chlorophyll a in high-phosphorus lakes, and oxygen demand had a stronger influence on the extent of anoxia in deep lakes. Taken together, these results support the existence of a positive feedback that could magnify the effects of climate change and other anthropogenic pressures driving the development of anoxia in lakes around the world.

Classification of Heart Failure Events by Severity: Insights From the VICTORIA Trial.

BACKGROUND: Hospitalization due to heart failure (HFH) is a major source of morbidity, consumes significant economic resources and is a key endpoint in HF clinical trials. HFH events vary in severity and implications, but they are typically considered equivalent when analyzing clinical trial outcomes. OBJECTIVES: We aimed to evaluate the frequency and severity of HF events, assess treatment effects and describe differences in outcomes by type of HF event in VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction). METHODS: VICTORIA compared vericiguat with placebo in patients with HF with reduced ejection fraction (< 45%) and a recent worsening HF event. All HFHs were prospectively adjudicated by an independent clinical events committee (CEC) whose members were blinded to treatment assignment. We evaluated the frequency and clinical impact of HF events by severity, categorized by highest intensity of HF treatment (urgent outpatient visit or hospitalization treated with oral diuretics, intravenous diuretics, intravenous vasodilators, intravenous inotropes, or mechanical support) and treatment effect by event categories. RESULTS: In VICTORIA, 2948 HF events occurred in 5050 enrolled patients. Overall total CEC HF events for vericiguat vs placebo were 43.9 vs 49.1 events/100 patient-years (P = 0.01). Hospitalization for intravenous diuretics was the most common type of HFH event (54%). HF event types differed markedly in their clinical implications for both in-hospital and post-discharge events. We observed no difference in the distribution of HF events between randomized treatment groups (P = 0.78). CONCLUSION: HF events in large global trials vary significantly in severity and clinical implications, which may have implications for more nuanced trial design and interpretation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT02861534).

Self-Reported Dysphagia and Psychosocial Health Among Community-Dwelling Older Adults: Results of a National Study.

BACKGROUND: The risk of dysphagia increases with age, affecting up to 33% of adults over the age of 65. Older adults with dysphagia are at increased risk for negative physical health outcomes such as aspiration pneumonia and death. However, the relationship between dysphagia and psychosocial health is uncertain in this population. OBJECTIVE: We aimed to assess the associations between dysphagia and psychosocial health among older adults (≥ 65) with self-reported dysphagia. DESIGN: We performed a cross-sectional assessment of the National Health and Aging Trends Study (NHATS) conducted in 2019. MAIN MEASURES: Weighted logistic and linear regression models were used to assess the relationship between self-reported dysphagia and psychosocial health using established patient-reported outcome measures including those for depression, anxiety, and social isolation previously used in NHATS analyses, while adjusting for demographics, comorbid conditions, and risk factors for dysphagia identified by purposeful selection. KEY RESULTS: Among the 4041 adults in this cohort, almost half (40%) were between 70 and 74 years old, more than half were female (55%), and a significantly higher proportion were White, non-Hispanic respondents (78.1%, p < 0.01) compared with other races and ethnicities. There were 428 (10.5%) respondents reporting dysphagia symptoms within the previous month. In the multivariable model, dysphagia was associated with significantly increased odds of anxiety (OR 1.33 [1.06, 1.67]) and a significantly decreased sense of well-being (coefficient - 1.10 [- 1.66, - 0.54]), but no association was detected for social isolation. CONCLUSIONS: When accounting for factors associated with underlying physical health status, self-reported dysphagia is independently associated with negative psychosocial health and warrants attention by healthcare providers. Future studies should aim to identify causal factors and the extent to which interventions may mitigate these factors.

Demographically-adjusted normative data among Latinos for the version 3 of the Alzheimer's Disease Centers' Neuropsychological Test Battery in the Uniform Data Set.

INTRODUCTION: We developed demographically-adjusted normative data for Spanish- and English-speaking Latinos on the Version 3.0 of the National Alzheimer's Coordinating Center Uniform Data Set Neuropsychological Battery (UDS3-NB). METHODS: Healthy Latino adults (N = 437) age 50-94 (191 Spanish- and 246 English-speaking) enrolled in Alzheimer's Disease Research Centers completed the UDS3-NB in their preferred language. Normative data were developed via multiple linear regression models on UDS3-NB raw scores stratified by language group with terms for demographic characteristics (age, years of formal education, and sex). RESULTS: Younger age and more years of education were associated with better performance on most tests in both language groups, with education being particularly influential on raw scores among Spanish-speakers. Sex effects varied across tests and language groups. DISCUSSION: These normative data are a crucial step toward improving diagnostic accuracy of the UDS3-NB for neurocognitive disorders among Latinos in the United States and addressing disparities in Alzheimer's disease and related dementias. HIGHLIGHTS: We developed normative data on the UDS3-NB for Latinos in the US ages 50-94. Younger age and more years of education were linked to better raw scores in several cognitive tests. Education was particularly influential on raw scores among Spanish-speakers. Sex effects varied across tests and between English- and Spanish-speaking Latinos. These normative data might improve diagnostic accuracy of the UDS3-NB among Latinos.

World regional differences in outcomes for patients with peripheral artery disease: Insights from the EUCLID trial.

Regional variations exist in the epidemiology of peripheral artery disease (PAD), in comorbidities, use of secondary prevention, and outcomes. Large studies of these variations in worldwide populations are rare. The EUCLID (Examining Use of tiCagreLor In peripheral artery Disease) trial included 13,885 patients with PAD from four geographical regions (Central/South America, Europe, Asia, North America) and compared monotherapy with ticagrelor and clopidogrel. Inclusion criteria were either an ankle-brachial index < 0.80 or a prior revascularization. The primary efficacy endpoint was time to first occurrence of any event in the composite of cardiovascular death, myocardial infarction, or ischemic stroke and did not differ between the study arms. This post hoc analysis of EUCLID confirmed that regional differences occurred in the inclusion criteria with more prior revascularization in North America (73.9%) and Asia (72.5%) compared with Central/South America (34.0%) and Europe (51.6%). The characteristics of patients also differed. Prior amputation at baseline was most frequent in Central/South America (6.3%) compared with other regions (1.6-2.8%). A history of stroke was most common in Asia, coronary heart disease in North America, and diabetes in Central/South America compared with other regions. The incidence of outcomes in patients with PAD varied by region. North America had the highest rate of the primary combined endpoint (5.97 events/100 patient-years). Corresponding rates were 4.80, 3.95, and 3.87 for Asia, Europe, and Central/South America, respectively. Hospitalization for acute limb ischemia (events/100 patient-years) was most frequent in Europe (0.75) and North America (0.74) compared with Asia (0.60) and Central/South America (0.33). Adjustment for inclusion criteria and relevant PAD characteristics did not have a major impact on these regional differences. Further adjustment for concomitant disease, risk factors, and preventive medication modified the regional differences only marginally. In conclusion, substantial regional differences were found in cardiovascular and limb outcomes in patients with PAD and were not explained by variation in the category of included patients, concomitant disease, risk factors, and prevention. Such differences, which may be due to variation in other factors such as background population rates or clinical care, need to be considered when designing and interpreting large international studies (ClinicalTrials.gov Identifier: NCT01732822).

Mercury, selenium, and fatty acids in the axial muscle of largemouth bass: evaluating the influence of seasonal and sexual changes in fish condition and reproductive status.

Largemouth bass (LMB, 265-475 mm) were collected to document whether changes in fish condition and reproductive status influenced the concentration of total mercury (Hg) and selenium (Se) in axial muscle by season and sex. The fatty acid (FA) composition of fish was also examined to describe seasonal and sexual differences and identify whether arachidonic acid (ARA) could be used as a biomarker of Hg toxicity. There was a trend for females to have lower (p < 0.062) Se concentrations than males. The concentration of Se for females during spring (mean ± SD, 686 ± 51 ng/g dw) was 15% lower than males (806 ± 67 ng/g dw). Lower Se concentrations in females than males continued through summer and fall. Concentration of Hg for females during spring (152 ± 39 ng/g ww) was also 59% lower than males (373 ± 303 ng/g ww), but the difference was not significant (p > 0.2). The percent of lipids was greatest in fall and winter (3%) and comprised primarily of omega-3 fatty acids (35 g/100 g lipid). Fish condition as measured by percent lipids and relative weight was negatively (p < 0.02) related to Hg concentration for females and males. Lipid content for both sexes was also positively (p < 0.05) related to the Se:Hg ratio. Relative weight was positively related to the Se:Hg ratio for females during all seasons (p = 0.014), but only during spring and summer for males (p < 0.007). A low Se:Hg value was associated with an elevation in ARA for both sexes and a reduced hepatosomatic index in males. Data suggested that females transferred muscle stores of Se and Hg to developing oocytes during spring. This study generates hypotheses regarding the physiological drivers of seasonal and sexual variability in Hg, Se, and FA in LMB that may be applicable to other species and have implications for fisheries health and management.

Detection of Pythium spp. in Golf Course Irrigation Systems.

Many Pythium spp. are causal agents of diseases of turfgrasses. Pythium spp. disseminate through irrigation systems in agricultural settings, and this study provides evidence that Pythium spp. also disseminate through golf course irrigation. Water samples were collected from irrigation heads and water sources at 10 golf courses in Missouri and Kansas, U.S.A. Samples were collected from 2018 to 2019 in April, July, and October. Phosphorus, nitrogen, and chloride concentrations were measured from irrigation head samples to determine if these parameters influence frequency of Pythium spp. detected. Pythium spp. were detected in samples through baiting and membrane filtration. Cultures were isolated on PARP media, and DNA was extracted from putative Pythium isolates. The internal transcribed spacer region was PCR-amplified and sequenced. Phylogenetic trees were constructed using representative sample sequences, sequences from seven morphologically identified reference isolates of Pythium, and similar GenBank accessions. Detected oomycete species include Lagenidium giganteum, Pythium biforme, Pythium insidiosum, Pythium marsipium, Pythium plurisporium, and Saprolegnia hypogyna. Twenty-one clades lacked species-level resolution, and 14 of these clades were associated with Pythium species. Clades A, C, D, E, I, and M contain Pythium species that cause root and crown rot on creeping bentgrass. Detected Pythium communities were dependent on the detection method used and sampling source. Pythium frequency and diversity were highest in April 2019. Sample temperature, sampling site, and chloride and nutrient concentrations did not influence Pythium frequency in samples. Irrigation systems using surface water sources contained at least three Pythium spp. over the course of 2 years.

Living with a Smoker and Physical Inactivity across Eight Years in High-Risk Medical Patients.

Recent research has demonstrated a link between living with a smoker and physical inactivity. However, no research has examined this issue in the context of recovery in medical patients. The present study broadens research on living with a smoker by applying it to physical inactivity in a group of high-risk medical patients with histories of cancer or cardiovascular disease compared to a control group without histories of these conditions. In addition, this study extends the time frame of research on living with a smoker in predicting physical inactivity to eight years. Participants were 76,758 women between 49 and 81 years of age from the Women's Health Initiative Observational Study. Data on living with a smoker were collected at baseline; data on physical activity were collected at baseline and annually from 3 to 8 years. Analyses utilized latent growth modeling. Patient status, compared to control status, was associated with more physical inactivity at baseline. Independent of patient status, living with a smoker predicted a significant increase in the odds of no moderate or strenuous exercise and a significant increase in the odds of no walking at baseline. The effect of living with a smoker on physical inactivity was stronger than that of patient status. Moreover, the living with a smoker effect on physical inactivity remained stable across eight years. These findings highlight an overlooked impediment to compliance with recommendations for lifestyle change among high-risk medical patients.

Risk of major cardiovascular and neurologic events with obstructive sleep apnea among patients with atrial fibrillation.

BACKGROUND: Obstructive sleep apnea (OSA) is a known risk factor for atrial fibrillation (AF). However, it remains unclear whether OSA is independently associated with worse cardiovascular and neurological outcomes in patients with AF. METHODS: We used the ORBIT-AF I and ORBIT-AF II to conduct a retrospective cohort study of 22,760 patients with AF with and without OSA. Adjusted multivariable Cox proportional hazards models was used to determine whether OSA was associated with increased risk for major adverse cardiac and neurologic events (MACNEs) (cardiovascular death, myocardial infarction, stroke/transient ischemic attack/non-central nervous system embolism (stroke/SE), and new-onset heart failure], combined and individually. RESULTS: A total of 4,045 (17.8%) patients had OSA at baseline. Median follow-up time was 1.5 (interquartile range: 1-2.2) years, and 1,895 patients experienced a MACNE. OSA patients were younger (median [interquartile range] 68 [61-75] years vs 74 [66-81] years), were more likely male (70.7% vs 55.3%), and had increased body mass index (median 34.6 kg/m2 [29.8-40.2] vs 28.7 kg/m2 [25.2-33.0]). Those with OSA had a higher prevalence of concomitant comorbidities such as diabetes, chronic obstructive pulmonary disease, and heart failure. OSA patients had higher use of antithrombotic therapy. After adjustment, the presence of OSA was significantly associated with MACNE (hazard ratio: 1.16 [95% CI: 1.03-1.31], P = .011). OSA was also an independent risk factor for stroke/SE beyond the CHA2DS2-VASc risk factors (HR: 1.38 [95% CI 1.12-1.70], P = .003) but not cardiovascular death, myocardial infarction, new-onset heart failure, or major bleeding. CONCLUSIONS: Among patients with AF, OSA is an independent risk factor for MACNE and, more specifically, stroke/SE.

VVI pacing with normal QRS duration and ventricular function: MOST trial findings relevant to leadless pacemakers.

BACKGROUND: Leadless pacemakers (LPs) provide ventricular pacing without the risks associated with transvenous leads and device pockets. LPs are appealing for patients who need pacing, but do not need defibrillator or cardiac resynchronization therapy. Most implanted LPs provide right ventricular pacing without atrioventricular synchrony (VVIR mode). The Mode Selection Trial in Sinus Node Dysfunction (MOST) showed similar outcomes in patients randomized to dual-chamber (DDDR) versus ventricular pacing (VVIR). We compared outcomes by pacing mode in LP-eligible patients from MOST. METHODS: Patients enrolled in the MOST study with an left ventricular ejection fraction (LVEF) >35%, QRS duration (QRSd) <120 ms and no history of ventricular arrhythmias or prior implantable cardioverter defibrillators were included (LP-eligible population). Cox proportional hazards models were used to test the association between pacing mode and death, stroke or heart failure (HF) hospitalization and atrial fibrillation (AF). RESULTS: Of the 2010 patients enrolled in MOST, 1284 patients (64%) met inclusion criteria. Baseline characteristics were well balanced across included patients randomized to DDDR (N = 630) and VVIR (N = 654). Over 4 years of follow-up, there was no association between pacing mode and death, stroke or HF hospitalization (VVIR HR 1.28 [0.92-1.75]). VVIR pacing was associated with higher risk of AF (HR 1.32 [1.08-1.61], P = .007), particularly in patients with no history of AF (HR 2.38 [1.52-3.85], P < .001). CONCLUSION: In patients without reduced LVEF or prolonged QRSd who would be eligible for LP, DDDR, and VVIR pacing demonstrated similar rates of death, stroke or HF hospitalization; however, VVIR pacing significantly increased the risk of AF development.

Physical, Chemical, and Biological Factors that Contribute to the Variability of Mercury Concentrations in Largemouth Bass Micropterus salmoides from Missouri Reservoirs.

Large-bodied predatory sportfish from Missouri reservoirs can contain elevated methylmercury concentrations that are of concern to the health of consumers. The concentration of total mercury (tHg) in the muscle (which > 95% is in the methylated-Hg form) of harvestable-sized largemouth bass (Micropterus salmoides; LMB) was examined to determine which factors contributed to the variability of tHg concentration in sportfish populations among Missouri reservoirs. Mean tHg concentrations in LMB from each reservoir were compared to physical and chemical characteristics of the reservoir and to biological attributes of each LMB population. Low concentrations of tHg (70-170 ng/g wet weight) in LMB from large reservoirs (surface area ≥ 35,680 acres) were likely related to the dilution of chemical Hg forms with water volume and depth. The highest tHg concentrations in LMB (268-542 ng/g) were from reservoirs with low particulate inorganic material (< 1.5 mg/L) and chlorophyll a concentrations (< 14.6 µg/L), and from LMB populations with a low proportion of large fish (proportional size distribution of LMB > 12 inches was < 33%). These relationships suggest that resource competition among LMB likely contributed to tHg bioaccumulation in reservoirs < 930 acres. Small reservoirs located in northern Missouri also may have greater methylation potential due to warmer water temperatures and anoxic conditions, but more data are needed to confirm these interactions. Fish consumption advisories for reservoirs with large surface area and volume could be reduced from one fish meal per month to one per week. To improve Missouri fisheries and protect consumers, management strategies to limit methylation and improve fish growth should be considered to reduce methylmercury bioaccumulation in small- and medium-sized reservoirs.

Ecology under lake ice.

Winter conditions are rapidly changing in temperate ecosystems, particularly for those that experience periods of snow and ice cover. Relatively little is known of winter ecology in these systems, due to a historical research focus on summer 'growing seasons'. We executed the first global quantitative synthesis on under-ice lake ecology, including 36 abiotic and biotic variables from 42 research groups and 101 lakes, examining seasonal differences and connections as well as how seasonal differences vary with geophysical factors. Plankton were more abundant under ice than expected; mean winter values were 43.2% of summer values for chlorophyll a, 15.8% of summer phytoplankton biovolume and 25.3% of summer zooplankton density. Dissolved nitrogen concentrations were typically higher during winter, and these differences were exaggerated in smaller lakes. Lake size also influenced winter-summer patterns for dissolved organic carbon (DOC), with higher winter DOC in smaller lakes. At coarse levels of taxonomic aggregation, phytoplankton and zooplankton community composition showed few systematic differences between seasons, although literature suggests that seasonal differences are frequently lake-specific, species-specific, or occur at the level of functional group. Within the subset of lakes that had longer time series, winter influenced the subsequent summer for some nutrient variables and zooplankton biomass.

Long-term changes in hypoxia and soluble reactive phosphorus in the hypolimnion of a large temperate lake: consequences of a climate regime shift.

The (Lower) Lake of Zurich provides an ideal system for studying the long-term impact of environmental change on deep-water hypoxia because of its sensitivity to climatic forcing, its history of eutrophication and subsequent oligotrophication, and the quality and length of its data set. Based on 39 years (1972-2010) of measured profiles of temperature, oxygen concentration and phosphorus (P) concentration, the potentially confounding effects of oligotrophication and climatic forcing on the occurrence and extent of deep-water hypoxia in the lake were investigated. The time-series of Nürnberg's hypoxic factor (HF) for the lake can be divided into three distinct segments: (i) a segment of consistently low HF from 1972 to the late-1980s climate regime shift (CRS); (ii) a transitional segment between the late-1980s CRS and approximately 2000 within which the HF was highly variable; and (iii) a segment of consistently high HF thereafter. The increase in hypoxia during the study period was not a consequence of a change in trophic status, as the lake underwent oligotrophication as a result of reduced external P loading during this time. Instead, wavelet analysis suggests that changes in the lake's mixing regime, initiated by the late-1980s CRS, ultimately led to a delayed but abrupt decrease in the deep-water oxygen concentration, resulting in a general expansion of the hypoxic zone in autumn. Even after detrending to remove long-term effects, the concentration of soluble reactive P in the bottom water of the lake was highly correlated with various measures of hypoxia, providing quantitative evidence supporting the probable effect of hypoxia on internal P loading. Such climate-induced, ecosystem-scale changes, which may result in undesirable effects such as a decline in water quality and a reduction in coldwater fish habitats, provide further evidence for the vulnerability of large temperate lakes to predicted increases in global air temperature.

Anti-CMV IgG Seropositivity is Associated with Plasma Biomarker Evidence of Amyloid-ß Accumulation.

Background: Some human studies have identified infection with cytomegalovirus (CMV), a member of the alpha herpesvirus family, as a risk factor for Alzheimer's disease and related dementias (ADRD). To our knowledge, no studies have evaluated associations of CMV seropositivity with plasma biomarkers of ADRD risk in middle-aged adults. Objective: In participants recruited for an exercise study, we evaluated cross-sectional associations of CMV seropositivity with: Aß42/Aß40 ratio, a low ratio suggestive of central nervous system Aß accumulation; glial fibrillary acidic protein (GFAP), a measure of neuroinflammation; and neurofilament light (NfL), a measure of neurodegeneration. Methods: Anti-CMV IgG was quantified by ELISA. Plasma ADRD biomarkers were quantified using the ultrasensitive SIMOA assay. We used linear regression to evaluate associations of CMV seropositivity with the ADRD biomarkers, adjusting for age, sex, and race (n = 303; Age = 55.7±9.2 years). For ADRD biomarkers significantly associated with CMV seropositivity, we evaluated continuous associations of anti-CMV IgG levels with the ADRD biomarkers, excluding CMV seronegative participants. Results: 53% of participants were CMV seropositive. CMV seropositivity was associated with a lesser Aß42/Aß40 ratio (ß=-3.02e-03 95% CI [-5.97e-03, -7.18e-05]; p = 0.045). In CMV seropositive participants, greater anti-CMV IgG levels were associated with a lesser Aß42/Aß40 ratio (ß=-4.85e-05 95% CI[-8.45e-05, -1.25e-05]; p = 0.009). CMV seropositivity was not associated with plasma GFAP or NfL in adjusted analyses. Conclusions: CMV seropositivity was associated with a lesser plasma Aß42/Aß40 ratio. This association may be direct and causally related to CMV neuro-cytotoxicity or may be indirect and mediated by inflammatory factors resulting from CMV infection burden and/or the immune response.

What makes a cyanobacterial bloom disappear? A review of the abiotic and biotic cyanobacterial bloom loss factors.

Cyanobacterial blooms present substantial challenges to managers and threaten ecological and public health. Although the majority of cyanobacterial bloom research and management focuses on factors that control bloom initiation, duration, toxicity, and geographical extent, relatively little research focuses on the role of loss processes in blooms and how these processes are regulated. Here, we define a loss process in terms of population dynamics as any process that removes cells from a population, thereby decelerating or reducing the development and extent of blooms. We review abiotic (e.g., hydraulic flushing and oxidative stress/UV light) and biotic factors (e.g., allelopathic compounds, infections, grazing, and resting cells/programmed cell death) known to govern bloom loss. We found that the dominant loss processes depend on several system specific factors including cyanobacterial genera-specific traits, in situ physicochemical conditions, and the microbial, phytoplankton, and consumer community composition. We also address loss processes in the context of bloom management and discuss perspectives and challenges in predicting how a changing climate may directly and indirectly affect loss processes on blooms. A deeper understanding of bloom loss processes and their underlying mechanisms may help to mitigate the negative consequences of cyanobacterial blooms and improve current management strategies.

Smoking status, physical health-related quality of life, and mortality in middle-aged and older women.

INTRODUCTION: Women who smoke, particularly older women, have been relatively neglected in smoking research. There is a lack of knowledge concerning the relation of level of smoking to quality of life and mortality among middle-aged and older women smokers. METHODS: This study examined the relation of smoking status to physical health-related quality of life (PHRQL) and total mortality in women in the Women's Health Initiative (WHI) Observational Study. Participants were 90,849 postmenopausal women, who were an average age of 63.6 years at baseline. Analyses used multiple linear and Cox proportional hazards regression and controlled for age, educational level, and ethnicity. Never-smokers were the reference group. RESULTS: We found that smoking status was significantly related to PHRQL cross-sectionally at baseline and prospectively at a 3-year follow-up, with those who smoked having lower PHRQL. Heavier smokers showed large, clinically meaningful associations with PHRQL and light smokers showed small associations. In addition, we found that the smoking status at baseline was significantly related to 10-year total mortality. Both light and heavier smoking at baseline significantly correlated with higher mortality risk; however, the relationship of smoking to mortality was dose dependent. Among former smokers, those who had smoked longer showed significantly lower PHRQL and significantly increased mortality risk. CONCLUSIONS: Findings suggest that the risks of smoking may not be evident to light smokers and that educational interventions targeted to middle-aged and older women stressing the consequences of light smoking may be particularly beneficial.