Klotho and Clinical Outcomes in CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

RATIONALE & OBJECTIVE: Klotho deficiency may affect clinical outcomes in chronic kidney disease (CKD) through fibroblast growth factor-23 (FGF23)-dependent and -independent pathways. However, the association between circulating Klotho and clinical outcomes in CKD remains unresolved and was the focus of this study. STUDY DESIGN: Prospective observational study. SETTING & PARTICIPANTS: 1,088 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study with an estimated glomerular filtration rate (eGFR) of 20-70mL/min/1.73m2. EXPOSURE: Plasma Klotho level at the year-1 study visit. OUTCOMES: 5-year risks of all-cause mortality, heart failure hospitalization, atherosclerotic cardiovascular events, and a composite kidney end point that comprised a sustained 50% decrease in eGFR, dialysis, kidney transplant, or eGFR<15mL/min/1.73m2. ANALYTICAL APPROACH: We divided Klotho into 6 groups to account for its nonnormal distribution. We used Cox proportional hazards regression and subdistribution hazards models to compare survival and clinical outcomes, respectively, between Klotho groups. We sequentially adjusted for demographic characteristics, kidney function, cardiovascular risk factors, sample age, and FGF23. RESULTS: Mean eGFR was 42mL/min/1.73m2, and median Klotho concentration was 0.31ng/mL (IQR, 0.10-3.27ng/mL). When compared with the lowest Klotho group, survival (HR, 0.77; 95% CI, 0.32-1.89), heart failure hospitalization (HR, 1.10; 95% CI, 0.38-3.17), atherosclerotic cardiovascular events (HR, 1.19; 95% CI, 0.57-2.52), and CKD progression (HR, 1.05; 95% CI, 0.58-1.91) did not differ in the high Klotho group. In contrast, FGF23 was significantly associated with mortality and heart failure hospitalization independent of Klotho levels. LIMITATIONS: Despite adjustments, we cannot exclude the potential influence of residual confounding or sample storage on the results. A single measurement of plasma Klotho concentration may not capture Klotho patterns over time. CONCLUSIONS: In a large, diverse, well-characterized CKD cohort, Klotho was not associated with clinical outcomes, and Klotho deficiency did not confound the association of FGF23 with mortality or heart failure hospitalization. PLAIN-LANGUAGE SUMMARY: Klotho is a protein that is vital to mineral metabolism and aging and may protect against cardiovascular disease. Klotho levels decrease in chronic kidney disease (CKD), but the association between Klotho and clinical outcomes in CKD remains uncertain. In a prospective cohort study of more than 1,000 people with CKD, circulating Klotho levels were not associated with kidney disease progression, cardiovascular outcomes, or mortality. These results suggest that the decrease in circulating Klotho levels in CKD does not play a prominent role in the development of poor clinical outcomes.

Monitoring post-spawning movement, habitat use, and survival of adult anadromous rainbow smelt using acoustic telemetry in a New Hampshire estuary.

Anadromous rainbow smelt (Osmerus mordax, [Mitchill 1814]) are found along the northeast Atlantic coastline of North America, with their range now limited to north of Cape Cod, Massachusetts, USA. Although their anadromous life cycles are described broadly, gaps remain regarding how adult rainbow smelt use estuaries post-spawning, including movement behaviors, habitats used, and specific timing of emigration to coastal waters. In spring 2021, we used acoustic telemetry to characterize movements during and after the spawning season of rainbow smelt captured in tributaries to Great Bay, New Hampshire, USA, a large estuarine system near the southern edge of their range. Forty-four adult rainbow smelt (n = 35 male, n = 9 female) were tagged with Innovasea V5 180-kHz transmitters and an array of 22,180 kHz VR2W receivers were deployed throughout Great Bay to detect movements of tagged fish from March to October 2021. Rainbow smelt were detected 14,186 times on acoustic telemetry receivers, with 41 (93%) of the tagged individuals being detected at least once post-tagging. Individuals were detected moving between tributaries, revealing that rainbow smelt can use multiple rivers during the spawning season (March-April). Mark-recapture Cormack-Jolly-Seber models estimated 83% (95% confidence interval 66%-92%) of rainbow smelt survived to the mainstem Piscataqua River, and a minimum of 50% (22 of 44) reached the seaward-most receivers and were presumed to have survived emigration. Most individuals that survived remained in the estuary for multiple weeks (average = 19.47 ± 1.99 standard error days), displaying extended use of estuarine environments. Downstream movements occurred more frequently during ebb tides and upstream movements with flood tides, possibly a mechanism to reduce energy expenditures. Fish emigrated from the estuary by mid-May to the coastal Gulf of Maine. Our results underscore that rainbow smelt need access to a variety of habitats, including multiple tributaries and high-quality estuarine habitat, to complete their life cycle.

Characterizing the nuclear and cytoplasmic transcriptomes in developing and mature human cortex uncovers new insight into psychiatric disease gene regulation.

Transcriptome compartmentalization by the nuclear membrane provides both stochastic and functional buffering of transcript activity in the cytoplasm, and has recently been implicated in neurodegenerative disease processes. Although many mechanisms regulating transcript compartmentalization are also prevalent in brain development, the extent to which subcellular localization differs as the brain matures has yet to be addressed. To characterize the nuclear and cytoplasmic transcriptomes during brain development, we sequenced both RNA fractions from homogenate prenatal and adult human postmortem cortex using poly(A)+ and Ribo-Zero library preparation methods. We find that while many genes are differentially expressed by fraction and developmental expression changes are similarly detectable in nuclear and cytoplasmic RNA, the compartmented transcriptomes become more distinct as the brain matures, perhaps reflecting increased utilization of nuclear retention as a regulatory strategy in adult brain. We examined potential mechanisms of this developmental divergence including alternative splicing, RNA editing, nuclear pore composition, RNA-binding protein motif enrichment, and RNA secondary structure. Intron retention is associated with greater nuclear abundance in a subset of transcripts, as is enrichment for several splicing factor binding motifs. Finally, we examined disease association with fraction-regulated gene sets and found nuclear-enriched genes were also preferentially enriched in gene sets associated with neurodevelopmental psychiatric disorders. These results suggest that although gene-level expression is globally comparable between fractions, nuclear retention of transcripts may play an underappreciated role in developmental regulation of gene expression in brain, particularly in genes whose dysregulation is related to neuropsychiatric disorders.

Trends in Degree Conferrals, Degree-Associated Debt, and Employment Outcomes Among Undergraduate Public Health Degree Graduates, 2001‒2020.

Objectives. To characterize the trends in degree conferrals, degree-associated debt, and employment outcomes among undergraduate public health degree (UGPHD) graduates. Methods. We reported administrative data on degree conferrals from 2001 to 2020 from the National Center for Education Statistics (NCES). For alumni graduating from 2015 to 2019, we also reported degree-associated debt and earnings 1 year after graduation compiled by NCES. Finally, we utilized a data set on 1-year postgraduation employment outcomes for graduates from 2015 to 2020 from the Association of Schools and Programs of Public Health. Results. As of 2020, more than 18 000 UGPHDs were awarded each year, more than 140 000 in total over the past 20 years. UGPHD graduates are highly diverse, with more than 80% being women and 55% being individuals from communities of color. We find alumni worked mostly in for-profit organizations (34%), health care (28%), nonprofits (11%), academic organizations (10%), government (10%), and other (6%). Degree-associated debt was $24 000, and the median first-year earnings were $34 000. Conclusions. While growth in UGPHD conferrals has slowed, it remains among the fastest-growing degree in the nation. However, the limited pathways into government remains a significant challenge. (Am J Public Health. 2023;113(1):115-123. https://doi.org/10.2105/AJPH.2022.307113).

Experiences of caregiving with Alzheimer's disease in the LGBT community.

BACKGROUND: The goal of this paper is to develop a more thorough understanding of the experiences of LGBT older adults living with dementia and their caregivers. METHODS: A phenomenological approach using in-depth interviews with current or former caregivers of LGBT persons living with Alzheimer's disease (AD) was conducted. RESULTS: Participants ranged in age from 44-77 years old; 74% were lesbian, 16% gay, 5% straight, and 5% unknown. Five themes were identified from the analysis: Caregiver tension and isolation; financial stress & security; lack of social support & connection; engineering grief support, and entrapment of past and present stigma and discrimination. CONCLUSIONS: Discrimination related to LGBT status was an important theme over the participants' lives and occurred for several during dementia care. While other themes were similar to prior AD studies, LGBT status affected these other aspects of the caregiving experience. Findings can inform future programs that better meet needs of LGBT people and those who care for them.

Simplified Technique for Creating an Umbilicus with Scarless Caudal Aspect and Superior Hooding.

A non-aesthetic post-abdominoplasty umbilicus is known to be a significant concern for many patients who consider this procedure, due to its central and visible location. The goal of this method is to minimize the visible scar and create a natural-looking and aesthetically pleasing umbilicus. In this multimedia article, we illustrate our technique that is both reproducible and easy to perform. It produces a scarless caudal aspect, pleasant depth, and natural superior hooding appearance to the post-op umbilicus. Limitations of this technique are discussed.Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Autologous Versus Alloplastic Reconstruction for Patients with Obesity: A Systematic Review and Meta-analysis.

BACKGROUND: Autologous flaps may have superior outcomes when compared to implant breast reconstruction in patients with obesity. To date, no published review has illustrated the superiority of autologous to implant-based reconstruction in this study group in terms of aesthetics outcomes and surgical complications. METHODS: A systematic search was conducted on PubMed, Cochrane, Google Scholar, and Embase from inception to December 31, 2020. Studies comparing the outcomes (patient satisfaction and complications) of autologous versus implant-based reconstruction in patients with BMI > 30 were selected. RESULTS: The search yielded 1633 articles, of which 76 were assessed in full text. A total of 12 articles fit inclusion for qualitative review; of them, 7 were meta-analyzed. Autologous reconstruction had a lower incidence of infection (OR 0.74 [95% CI 0.59, 0.92]), hematoma/seroma formation (OR 0.34 [95% CI 0.23, 0.49]), and reconstructive failure (OR 0.47 [95% CI 0.36, 0.62]), but not skin necrosis (OR 0.95 [95% CI 0.73, 1.25]) or wound dehiscence (OR 1.03 [95% CI 0.72, 1.49]) when compared to implant-based reconstruction. Deep vein thrombosis (DVT) and pulmonary embolism occurred more frequently with autologous versus alloplastic reconstruction (OR 2.21 [95% CI 1.09, 4.49] for DVT and OR 2.49 [95% CI 1.13, 5.48] for PE). BREASTQ scores were higher for the autologous breast reconstruction when compared to implant-based group, but failed to reach significance (p value >0.05). CONCLUSION: The current evidence in the literature suggests that autologous breast reconstruction has lower surgical complication rate when compared to implant-based reconstruction at the expense of higher risk of thrombotic complications for patients with BMI > 30. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

High-field MRI using standard pulse sequences has moderate to substantial interobserver agreement and good accuracy for differentiation between intracranial extra-axial histiocytic sarcoma and meningioma in dogs.

Intracranial extra-axial histiocytic sarcoma shares common MRI features with meningioma. As histiocytic sarcoma carries a generally worse prognosis than meningioma, the ability to differentiate between these two neoplasms is of clinical value. The aim of this retrospective diagnostic accuracy and observer agreement study was to evaluate the accuracy and reliability of high-field MRI to differentiate between these two tumors, using standard pulse sequences and published MRI features. A total of 51 dogs were included (26 meningiomas and 25 histiocytic sarcomas). Magnetic resonance imaging examinations were independently assessed by three experienced board-certified radiologists, evaluating 18 imaging features. They were asked to assign each case to one of three categories (meningioma, histiocytic sarcoma, and undetermined). Agreement for the MRI diagnosis across all three reviewers was moderate (κ 0.54) while paired interobserver agreement ranged from moderate to substantial (κ 0.58-0.74) with percent agreement ranging between 86.1% and 87.7%. Overall, the probability of correctly diagnosing meningioma in a dog with this tumor ranged between 79.2% and 94.4%, and the probability of correctly diagnosing histiocytic sarcoma in a dog with this tumor ranged between 76.0% and 92.3%. The overall probability to diagnose the correct tumor, irrespective of type, ranged between 79.2% and 89.7%. Histiocytic sarcomas tended to have more extensive edema and more often had combined perilesional and distant meningeal enhancement affecting both pachy- and leptomeninges, while for meningiomas, meningeal enhancement tended to more commonly be perilesional and pachymeningeal. Imaging features that seemed more useful to make a correct diagnosis included "location/type of meningeal enhancement," "osseous changes in the adjacent neurocranium," "cystic changes," and "herniation severity."

SPEAQeasy: a scalable pipeline for expression analysis and quantification for R/bioconductor-powered RNA-seq analyses.

BACKGROUND: RNA sequencing (RNA-seq) is a common and widespread biological assay, and an increasing amount of data is generated with it. In practice, there are a large number of individual steps a researcher must perform before raw RNA-seq reads yield directly valuable information, such as differential gene expression data. Existing software tools are typically specialized, only performing one step-such as alignment of reads to a reference genome-of a larger workflow. The demand for a more comprehensive and reproducible workflow has led to the production of a number of publicly available RNA-seq pipelines. However, we have found that most require computational expertise to set up or share among several users, are not actively maintained, or lack features we have found to be important in our own analyses. RESULTS: In response to these concerns, we have developed a Scalable Pipeline for Expression Analysis and Quantification (SPEAQeasy), which is easy to install and share, and provides a bridge towards R/Bioconductor downstream analysis solutions. SPEAQeasy is portable across computational frameworks (SGE, SLURM, local, docker integration) and different configuration files are provided ( http://research.libd.org/SPEAQeasy/ ). CONCLUSIONS: SPEAQeasy is user-friendly and lowers the computational-domain entry barrier for biologists and clinicians to RNA-seq data processing as the main input file is a table with sample names and their corresponding FASTQ files. The goal is to provide a flexible pipeline that is immediately usable by researchers, regardless of their technical background or computing environment.

First-Destination Outcomes for 2015-2018 Public Health Graduates: Focus on Employment.

Objectives. To improve understanding of the future public health workforce by analyzing first-destination employment outcomes of public health graduates.Methods. We assessed graduate outcomes for those graduating in 2015-2018 using descriptive statistics and the Pearson χ2 test.Results. In our analysis of data on 53 463 graduates, we found that 73% were employed; 15% enrolled in further education; 5% entered a fellowship, internship, residency, volunteer, or service program; and 6% were not employed. Employed graduates went to work in health care (27%), corporations (24%), academia (19%), government (17%), nonprofit (12%), and other sectors (1%). In 2018, 9% of bachelor's, 4% of master's, and 2% of doctoral graduates were not employed but seeking employment.Conclusions. Today's public health graduates are successful in finding employment in various sectors. This new workforce may expand public health's reach and lead to healthier communities overall.Public Health Implications. With predicted shortages in the governmental public health workforce and expanding hiring because of COVID-19, policymakers need to work to ensure the supply of public health graduates meets the demands of the workforce.