A novel ultrasensitive assay for plasma p-tau217: Performance in individuals with subjective cognitive decline and early Alzheimer's disease.

INTRODUCTION: Detection of Alzheimer's disease (AD) pathophysiology among individuals with mild cognitive changes and those experiencing subjective cognitive decline (SCD) remains challenging. Plasma phosphorylated tau 217 (p-tau217) is one of the most promising of the emerging biomarkers for AD. However, accessible methods are limited. METHODS: We employed a novel p-tau217 immunoassay (University of Gothenburg [UGOT] p-tau217) in four independent cohorts (n = 308) including a cerebrospinal fluid (CSF) biomarker-classified cohort (Discovery), two cohorts consisting mostly of cognitively unimpaired (CU) and mild cognitively impaired (MCI) participants (MYHAT and Pittsburgh), and a population-based cohort of individuals with SCD (Barcelonaßeta Brain Research Center's Alzheimer's At-Risk Cohort [ß-AARC]). RESULTS: UGOT p-tau217 showed high accuracy (area under the curve [AUC] = 0.80-0.91) identifying amyloid beta (Aß) pathology, determined either by Aß positron emission tomography or CSF Aß42/40 ratio. In individuals experiencing SCD, UGOT p-tau217 showed high accuracy identifying those with a positive CSF Aß42/40 ratio (AUC = 0.91). DISCUSSION: UGOT p-tau217 can be an easily accessible and efficient way to screen and monitor patients with suspected AD pathophysiology, even in the early stages of the continuum.

Natural forcing of the North Atlantic nitrogen cycle in the Anthropocene.

Human alteration of the global nitrogen cycle intensified over the 1900s. Model simulations suggest that large swaths of the open ocean, including the North Atlantic and the western Pacific, have already been affected by anthropogenic nitrogen through atmospheric transport and deposition. Here we report an ∼130-year-long record of the 15N/14N of skeleton-bound organic matter in a coral from the outer reef of Bermuda, which provides a test of the hypothesis that anthropogenic atmospheric nitrogen has significantly augmented the nitrogen supply to the open North Atlantic surface ocean. The Bermuda 15N/14N record does not show a long-term decline in the Anthropocene of the amplitude predicted by model simulations or observed in a western Pacific coral 15N/14N record. Rather, the decadal variations in the Bermuda 15N/14N record appear to be driven by the North Atlantic Oscillation, most likely through changes in the formation rate of Subtropical Mode Water. Given that anthropogenic nitrogen emissions have been decreasing in North America since the 1990s, this study suggests that in the coming decades, the open North Atlantic will remain minimally affected by anthropogenic nitrogen deposition.

Ocean acidification affects coral growth by reducing skeletal density.

Ocean acidification (OA) is considered an important threat to coral reef ecosystems, because it reduces the availability of carbonate ions that reef-building corals need to produce their skeletons. However, while theory predicts that coral calcification rates decline as carbonate ion concentrations decrease, this prediction is not consistently borne out in laboratory manipulation experiments or in studies of corals inhabiting naturally low-pH reefs today. The skeletal growth of corals consists of two distinct processes: extension (upward growth) and densification (lateral thickening). Here, we show that skeletal density is directly sensitive to changes in seawater carbonate ion concentration and thus, to OA, whereas extension is not. We present a numerical model of Porites skeletal growth that links skeletal density with the external seawater environment via its influence on the chemistry of coral calcifying fluid. We validate the model using existing coral skeletal datasets from six Porites species collected across five reef sites and use this framework to project the impact of 21st century OA on Porites skeletal density across the global tropics. Our model predicts that OA alone will drive up to 20.3 ± 5.4% decline in the skeletal density of reef-building Porites corals.

Framed, Interactive Theory-Driven Texting: Effects of Message Framing on Health Behavior Change for Weight Loss.

More approaches to support weight control are needed, especially among racial minorities who shoulder a disproportionate obesity burden. Using an approach influenced by regulatory fit theory, we conducted a 28-day, 4-arm experimental trial with 89 obese adults recruited from urban, predominantly African American churches to ascertain the efficacy of framed text messages to motivate behaviors conducive to weight loss. Participants were assigned to receive message framing that was matched versus mismatched to their motivational orientation. Results were mixed overall; however, matched texts elicited greater motivation to change eating and exercise behavior, suggesting promise in using motivational approaches to tailor messages.

Reduced calcification and lack of acclimatization by coral colonies growing in areas of persistent natural acidification.

As the surface ocean equilibrates with rising atmospheric CO2, the pH of surface seawater is decreasing with potentially negative impacts on coral calcification. A critical question is whether corals will be able to adapt or acclimate to these changes in seawater chemistry. We use high precision CT scanning of skeletal cores of Porites astreoides, an important Caribbean reef-building coral, to show that calcification rates decrease significantly along a natural gradient in pH and aragonite saturation (Ωarag). This decrease is accompanied by an increase in skeletal erosion and predation by boring organisms. The degree of sensitivity to reduced Ωarag measured on our field corals is consistent with that exhibited by the same species in laboratory CO2 manipulation experiments. We conclude that the Porites corals at our field site were not able to acclimatize enough to prevent the impacts of local ocean acidification on their skeletal growth and development, despite spending their entire lifespan in low pH, low Ωarag seawater.

Oral transmucosal administration of dexmedetomidine for sedation in 4 dogs.

Injectable dexmedetomidine (DM) is widely used for sedation, restraint, anxiolysis, and analgesia in veterinary medicine. Oral transmucosal dexmedetomidine (OTM DM) has been evaluated in horses, cats, and humans, but not in dogs. In this case series, OTM DM (mean dose of 32.6 µg/kg body weight) was given in the buccal pouch to 4 aggressive dogs in a hospital setting. Two of the dogs were subsequently euthanized, and in the other 2, sedation was reversed with atipamezole. Satisfactory sedation was achieved in all cases.

Administration transmucosale orale de dexmédétomidine pour la sédation chez 4 chiens. La dexmédétomidine (DM) injectable est largement utilisée pour la sédation, la contention, l'anxiolyse et l'analgésie en médecine vétérinaire. La dexmédétomidine transmucosale orale (OTM DM) a été évaluée chez les chevaux, les chats et les humains, mais non chez les chiens. Dans cette série de cas, l'OTM DM (dose moyenne de 32,6 µg/kg de poids corporel) a été administrée via la muqueuse orale, en milieu hospitalier, à 4 chiens agressifs. Deux des chiens ont été subséquemment euthanasiés et, chez les 2 autres, l'éveil a été effectué avec de l'atipamézole. Une sédation satisfaisante a été obtenue dans tous les cas.(Traduit par Isabelle Vallières).

The Most Impactful Articles on the Shoulder Labrum From the United States or Europe, and Decreased Level of Evidence Is Associated With Increased Altmetric Attention Score.

Purpose: To use the top 100 articles pertaining to the shoulder labrum to understand the impact that social medial platforms have on the dissemination of shoulder research and to highlight bibliometric factors associated with Altmetric Attention Scores (AAS) to offer insight into the impact that social media platforms have on the dissemination, attention, and citation of shoulder research publications. Methods: This was a cross-sectional study. In January 2023, the Altmetric database was searched using the PubMed Medical Subject Headings terms "shoulder labrum." Articles with the greatest AAS were screened to exclude other topics unrelated to the labrum of the shoulder. The top 100 articles that met inclusion criteria were used in the final analysis. Bibliometric factors pertaining to each study were collected for further analysis of article characteristics in accordance with previous studies. Results: The Altmetric Database query yielded 619 studies. The top 100 articles with highest AAS were identified, mean Attestation Score was 24.85 ± 55.51, with a range of 7 to 460. The included articles represented 35 journals, with 57 articles attributed to 3 journals: American Journal of Sports Medicine (AJSM; 29%), Arthroscopy: The Journal of Arthroscopic & Related Surgery (Arthroscopy; 19%), and the Journal of Shoulder and Elbow Surgery (JSES; 9%). There was a significant increase in AAS for every decrease in the numerical Level of Evidence value for a study (P = .011) but no association between score and citation rate (P > 005). Conclusions: Top articles on the shoulder labrum, as defined by high AAS score, are most commonly original clinical research published in 1 of 3 sports medicine journals and performed in the United States or Europe. A decreased numerical Level of Evidence is associated with an increase in AAS score, but there is no association between AAS score and citation rate. Clinical Relevance: The increasing amount of science and health information shared freely through open-access journals, online servers, and numerous social media channels makes it difficult to measure the impact of research. Using measures such as the Altmetric Attention Score, in isolation or addition to measures of researcher or journal impact, has the potential to provide comprehensive information about the impact of research in the modern world.

Interaction Between State-Level Cigarette Prices and County-Level Tobacco 21 Coverage on Cigarette Smoking Outcomes Among US Adolescents.

PURPOSE: To examine whether Tobacco 21 (T21) law coverage moderated associations between cigarette prices and adolescent smoking and associated disparities. METHODS: We used nationally representative, repeated cross-sectional 2014-2020 Monitoring the Future study data (n = 20,547-96,083) to examine associations between state-level average cigarette price per pack and county-level T21 coverage (100% vs. < 100%) on past 30-day smoking participation, first and daily cigarette smoking initiation, and smoking intentions in US adolescents in eighth, 10th, and 12th grade. We implemented weighted, grade-stratified, modified Poisson regression models to test for interactions between price and T21 coverage for each outcome. We also tested for disparities by sex, race and ethnicity, parental education, and college educational expectations. RESULTS: Higher cigarette prices were associated with a lower probability of past 30-day smoking participation among eighth graders in counties with < 100% T21 coverage (average marginal effect = -0.003, 95% confidence interval = -0.006, 0.000) but not among eighth graders in counties with 100% T21 coverage (average marginal effect = 0.001, 95% confidence interval = -0.001, 0.004) (p for interaction = 0.005). There were no associations with other smoking outcomes or grades or evidence of differential associations by sociodemographic factors. DISCUSSION: Our findings suggested that higher cigarette prices were associated with lower adolescent smoking among eighth graders living in counties with < 100% T21 coverage. However, no such association was observed in other grades or smoking outcomes. Further investigation is necessary to determine the best combination of policies to reduce adolescent smoking, related sociodemographic disparities, and the use of other tobacco products in areas with fewer tobacco control policies.

Alzheimer blood biomarkers: practical guidelines for study design, sample collection, processing, biobanking, measurement and result reporting.

Alzheimer's disease (AD), the most common form of dementia, remains challenging to understand and treat despite decades of research and clinical investigation. This might be partly due to a lack of widely available and cost-effective modalities for diagnosis and prognosis. Recently, the blood-based AD biomarker field has seen significant progress driven by technological advances, mainly improved analytical sensitivity and precision of the assays and measurement platforms. Several blood-based biomarkers have shown high potential for accurately detecting AD pathophysiology. As a result, there has been considerable interest in applying these biomarkers for diagnosis and prognosis, as surrogate metrics to investigate the impact of various covariates on AD pathophysiology and to accelerate AD therapeutic trials and monitor treatment effects. However, the lack of standardization of how blood samples and collected, processed, stored analyzed and reported can affect the reproducibility of these biomarker measurements, potentially hindering progress toward their widespread use in clinical and research settings. To help address these issues, we provide fundamental guidelines developed according to recent research findings on the impact of sample handling on blood biomarker measurements. These guidelines cover important considerations including study design, blood collection, blood processing, biobanking, biomarker measurement, and result reporting. Furthermore, the proposed guidelines include best practices for appropriate blood handling procedures for genetic and ribonucleic acid analyses. While we focus on the key blood-based AD biomarkers for the AT(N) criteria (e.g., amyloid-beta [Aß]40, Aß42, Aß42/40 ratio, total-tau, phosphorylated-tau, neurofilament light chain, brain-derived tau and glial fibrillary acidic protein), we anticipate that these guidelines will generally be applicable to other types of blood biomarkers. We also anticipate that these guidelines will assist investigators in planning and executing biomarker research, enabling harmonization of sample handling to improve comparability across studies.

A novel ultrasensitive assay for plasma p-tau217: performance in individuals with subjective cognitive decline and early Alzheimer's disease.

INTRODUCTION: Detection of Alzheimer's disease (AD) pathophysiology among cognitively unimpaired individuals and those experiencing subjective cognitive decline (SCD) remains challenging. Plasma p-tau217 is one of the most promising of the emerging biomarkers for AD. However, accessible methods are limited. METHODS: We employed a novel p-tau217 immunoassay (UGOT p-tau217) in four independent cohorts (n=308) including a cerebrospinal fluid (CSF) biomarker-classified cohort (Discovery), two cohorts consisting mostly of cognitively unimpaired participants (MYHAT and Pittsburgh), and a population-based cohort of individuals with SCD (ß-AARC). RESULTS: UGOT p-tau217 showed high accuracy (AUC= 0.80-0.91) identifying Aß pathology, determined either by Aß positron emission tomography or CSF Aß42/40 ratio. In individuals experiencing SCD, UGOT p-tau217 showed high accuracy identifying those with a positive CSF Aß42/40 ratio (AUC= 0.91). DISCUSSION: UGOT p-tau217 can be an easily accessible and efficient way to screen and monitor patients with suspected AD pathophysiology, even in the early stages of the continuum.

Early AD pathology in a [C-11]PiB-negative case: a PiB-amyloid imaging, biochemical, and immunohistochemical study.

Amyloid-ß (Aß) deposits are detectable in the brain in vivo using positron emission tomography (PET) and [C-11]-labeled Pittsburgh Compound B ([C-11]PiB); however, the sensitivity of this technique is not well understood. In this study, we examined Aß pathology in an individual who had clinical diagnoses of probable dementia with Lewy bodies and possible Alzheimer's disease (AD) but with no detectable [C-11]PiB PET retention ([C-11]PiB(-)) when imaged 17 months prior to death. Brain samples were processed in parallel with region-matched samples from an individual with a clinical diagnosis of probable AD and a positive [C-11]PiB PET scan ([C-11]PiB(+)) when imaged 10 months prior to death. In the [C-11]PiB(-) case, Aß plaques were sparse, occupying less than 2% cortical area, and were weakly labeled with 6-CN-PiB, a highly fluorescent derivative of PiB. In contrast, Aß plaques occupied up to 12% cortical area in the [C-11]PiB(+) case, and were intensely labeled with 6-CN-PIB. The [C-11]PiB(-) case had low levels of [H-3]PiB binding (< 100 pmol/g) and Aß1-42 (< 500 pmol/g) concentration except in the frontal cortex where Aß1-42 values (788 pmol/g) approached cortical values in the [C-11]PiB(+) case (800-1, 700 pmol/g). In several cortical regions of the [C-11]PiB(-) case, Aß1-40 levels were within the range of cortical Aß1-40 values in the [C-11]PiB(+) case. Antemortem [C-11]PiB DVR values correlated well with region-matched postmortem measures of Aß1-42 and Aß1-40 in the [C-11]PiB(+), and with Aß1-42 only in the [C-11]PiB(-) case. The low ratios of [H-3]PiB binding levels to Aß concentrations and 6-CN-PiB to Aß plaque loads in the [C-11]PiB(-) case indicate that Aß pathology in the brain may be associated with low or undetectable levels of [C-11]PiB retention. Studies in greater numbers of [C-11]PiB PET autopsy cases are needed to define the Aß concentration and [H-3]PiB binding levels required to produce a positive [C-11]PiB PET signal.

Palau's warmest reefs harbor thermally tolerant corals that thrive across different habitats.

Ocean warming is killing corals, but heat-tolerant populations exist; if protected, they could replenish affected reefs naturally or through restoration. Palau's Rock Islands experience consistently higher temperatures and extreme heatwaves, yet their diverse coral communities bleach less than those on Palau's cooler outer reefs. Here, we combined genetic analyses, bleaching histories and growth rates of Porites cf. lobata colonies to identify thermally tolerant genotypes, map their distribution, and investigate potential growth trade-offs. We identified four genetic lineages of P. cf. lobata. On Palau's outer reefs, a thermally sensitive lineage dominates. The Rock Islands harbor two lineages with enhanced thermal tolerance; one of which shows no consistent growth trade-off and also occurs on several outer reefs. This suggests that the Rock Islands provide naturally tolerant larvae to neighboring areas. Finding and protecting such sources of thermally-tolerant corals is key to reef survival under 21st century climate change.

The medical spa: an opportunity or nightmare?

Nonsurgical cosmetic procedures have become increasingly common and important to plastic surgery practices. Many physicians have either opened a medical spa or have thought about integrating a medical spa into their aesthetic practices. The authors (plastic surgeon and marketing professional) have shared their views on opening a medical spa and the trials they went through. This article describes the positives and negatives of opening a spa from construction through personnel.

The Case for a Health at Every Size Approach for Chronic Disease Risk Reduction in Women of Color.

The conventional approach to chronic disease management in women of color is a dieting-for-weight-loss approach, which has not been proven to be effective. The purpose of this article is to highlight the shortcomings of the dieting-for-weight-loss approach and demonstrate the potential efficacy of the Health at Every Size approach when working with women of color to prevent and address chronic diseases. The article's areas of focus are weight stigma, bias, and size discrimination; the implications of differing weight perceptions and motivations for change; and weight as the primary determinant of health and biological factors affecting weight.

Repeat bleaching of a central Pacific coral reef over the past six decades (1960-2016).

The oceans are warming and coral reefs are bleaching with increased frequency and severity, fueling concerns for their survival through this century. Yet in the central equatorial Pacific, some of the world's most productive reefs regularly experience extreme heat associated with El Niño. Here we use skeletal signatures preserved in long-lived corals on Jarvis Island to evaluate the coral community response to multiple successive heatwaves since 1960. By tracking skeletal stress band formation through the 2015-16 El Nino, which killed 95% of Jarvis corals, we validate their utility as proxies of bleaching severity and show that 2015-16 was not the first catastrophic bleaching event on Jarvis. Since 1960, eight severe (>30% bleaching) and two moderate (<30% bleaching) events occurred, each coinciding with El Niño. While the frequency and severity of bleaching on Jarvis did not increase over this time period, 2015-16 was unprecedented in magnitude. The trajectory of recovery of this historically resilient ecosystem will provide critical insights into the potential for coral reef resilience in a warming world.

Mass coral mortality under local amplification of 2 °C ocean warming.

A 2 °C increase in global temperature above pre-industrial levels is considered a reasonable target for avoiding the most devastating impacts of anthropogenic climate change. In June 2015, sea surface temperature (SST) of the South China Sea (SCS) increased by 2 °C in response to the developing Pacific El Niño. On its own, this moderate, short-lived warming was unlikely to cause widespread damage to coral reefs in the region, and the coral reef "Bleaching Alert" alarm was not raised. However, on Dongsha Atoll, in the northern SCS, unusually weak winds created low-flow conditions that amplified the 2 °C basin-scale anomaly. Water temperatures on the reef flat, normally indistinguishable from open-ocean SST, exceeded 6 °C above normal summertime levels. Mass coral bleaching quickly ensued, killing 40% of the resident coral community in an event unprecedented in at least the past 40 years. Our findings highlight the risks of 2 °C ocean warming to coral reef ecosystems when global and local processes align to drive intense heating, with devastating consequences.

21st-century rise in anthropogenic nitrogen deposition on a remote coral reef.

With the rapid rise in pollution-associated nitrogen inputs to the western Pacific, it has been suggested that even the open ocean has been affected. In a coral core from Dongsha Atoll, a remote coral reef ecosystem, we observe a decline in the 15N/14N of coral skeleton-bound organic matter, which signals increased deposition of anthropogenic atmospheric N on the open ocean and its incorporation into plankton and, in turn, the atoll corals. The first clear change occurred just before 2000 CE, decades later than predicted by other work. The amplitude of change suggests that, by 2010, anthropogenic atmospheric N deposition represented 20 ± 5% of the annual N input to the surface ocean in this region, which appears to be at the lower end of other estimates.

Mitigation of Coral Reef Warming Across the Central Pacific by the Equatorial Undercurrent: A Past and Future Divide.

Global climate models (GCMs) predict enhanced warming and nutrient decline across the central tropical Pacific as trade winds weaken with global warming. Concurrent changes in circulation, however, have potential to mitigate these effects for equatorial islands. The implications for densely populated island nations, whose livelihoods depend on ecosystem services, are significant. A unique suite of in situ measurements coupled with state-of-the-art GCM simulations enables us to quantify the mitigation potential of the projected circulation change for three coral reef ecosystems under two future scenarios. Estimated historical trends indicate that over 100% of the large-scale warming to date has been offset locally by changes in circulation, while future simulations predict a warming mitigation effect of only 5-10% depending on the island. The pace and extent to which GCM projections overwhelm historical trends will play a key role in defining the fate of marine ecosystems and island communities across the tropical Pacific.

Preoperative Duplex Scanning is a Helpful Diagnostic Tool in Neurogenic Thoracic Outlet Syndrome.

OBJECTIVE: To evaluate the diagnostic role of venous and arterial duplex scanning in neurogenic thoracic outlet syndrome (NTOS). METHODS: Retrospective review of patients who underwent duplex ultrasonography prior to first rib resection and scalenectomy (FRRS) for NTOS from 2005 to 2013. Abnormal scans included ipsilateral compression (IC) with abduction of the symptomatic extremity (>50% change in subclavian vessel flow), contralateral (asymptomatic side) compression (CC) or bilateral compression (BC). RESULTS: A total of 143 patients (76% female, average age 34, range 13-59) underwent bilateral preoperative duplex scanning. Ipsilateral compression was seen in 44 (31%), CC in 12 (8%), and BC in 14 (10%). Seventy-three (51%) patients demonstrated no compression. Patients with IC more often experienced intraoperative pneumothoraces (49% vs. 25%, P < .05) and had positive Adson tests (86% vs. 61%, P < .02). CONCLUSION: Compression of the subclavian vein or artery on duplex ultrasonography can assist in NTOS diagnosis. Ipsilateral compression on abduction often correlates with Adson testing.