Lipid trajectories improve risk models for Alzheimer's disease and mild cognitive impairment.

In this retrospective, case-control study, we tested the hypothesis that blood-lipid concentrations during the decade prior to cognitive symptom onset can inform risk prediction for Alzheimer's disease (AD) and stable mild cognitive impairment (MCI). Clinically well-characterized cases were diagnosed using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria; MCI cases had been stable for ≥5 years; and controls were propensity matched to cases at symptom onset (MCI: 116 cases, 435 controls; AD: 215 cases, 483 controls). Participants were grouped based on (i) longitudinal trajectories and (ii) quintile of variability independent of the mean (VIM) for total cholesterol, HDL-C, low-density lipoprotein cholesterol, non-HDL-C, and ln(triglycerides).

An Integrative Migraine Polygenic Risk Score Is Associated with Age at Onset But Not Chronification.

: Genome-wide association studies (GWASs) demonstrate a complex genetic landscape for migraine risk. Migraine polygenic risk scores (PRSs) developed from GWAS data may have utility for predicting disease course. We analyzed the strength of association between an integrative migraine PRS and age at onset and chronification.

High concordance between urine toxicology results and self-reported fentanyl use in Nevada and New Mexico.

Background: Co-use of stimulants and opioids is often deliberate. However, the possibility remains that some people are unintentionally consuming fentanyl. To advance understanding of overdose risk, we examined the rate of concordance between self-reported fentanyl use and corresponding urine toxicology screen results.

Clathrate Hydrate-Solid Surface Adhesive Shear Strength Measurements on Carbon Steel Surfaces.

Oil and gas flowlines operating in subsea or cold terrestrial environments face the risk of forming hydrate deposits and plugs. The pressure differential across a hydrate plug can cause the plug to detach from the pipe wall and travel through the pipeline, potentially impacting a bend or inline equipment, causing damage or injury to personnel. Therefore, the hydrate-solid adhesive shear strength is of interest in estimating the maximum allowable differential pressure across a plug during depressurization procedures before the plug is likely to detach from the pipe wall.

Gross morphology and adhesion-associated physical properties of Drosophila larval salivary gland glue secretion.

One of the major functions of the larval salivary glands (SGs) of many Drosophila species is to produce a massive secretion during puparium formation. This so-called proteinaceous glue is exocytosed into the centrally located lumen, and subsequently expectorated, serving as an adhesive to attach the puparial case to a solid substrate during metamorphosis. Although this was first described almost 70 years ago, a detailed description of the morphology and mechanical properties of the glue is largely missing.

Characteristics associated with response to subcutaneously administered anti-CGRP monoclonal antibody medications in a real-world community cohort of persons living with migraine: A retrospective clinical and genetic study.

Objective: To evaluate response to anti-calcitonin gene-related peptide (CGRP) migraine preventives in a real-world community cohort of persons living with migraine and to identify clinical and genetic characteristics associated with efficacious response.

Background: Erenumab-aooeb, fremanezumab-vrfm, and galcanezumab-gnlm target CGRP or its receptor; however, many patients are non-responsive.

Methods: In this retrospective clinical and genetic study, we identified 1077 adult patients who satisfied the International Classification of Headache Disorders, 3rd edition, criteria for migraine without aura, migraine with aura, or chronic migraine and who were prescribed an anti-CGRP migraine preventive between May 2018 and May 2021.

How best to diagnose and manage abdominal aortic aneurysms.

The evidence summarized here can help guide your approach to this life-threatening condition that often goes undetected until rupture.

Multifactorial assessment of Parkinson's disease course and outcomes using trajectory modeling in a multiethnic, multisite cohort - extension of the LONG-PD study.

Background: The severity, progression, and outcomes of motor and non-motor symptoms in Parkinson's disease (PD) are quite variable. Following PD cohorts holds promise for identifying predictors of disease severity and progression.

Methods: PD patients ( = 871) were enrolled at five sites.

Paleolakes and socioecological implications of last glacial "greening" of the South African interior.

Determining the timing and drivers of Pleistocene hydrological change in the interior of South Africa is critical for testing hypotheses regarding the presence, dynamics, and resilience of human populations. Combining geological data and physically based distributed hydrological modeling, we demonstrate the presence of large paleolakes in South Africa's central interior during the last glacial period, and infer a regional-scale invigoration of hydrological networks, particularly during marine isotope stages 3 and 2, most notably 55 to 39 ka and 34 to 31 ka. The resulting hydrological reconstructions further permit investigation of regional floral and fauna responses using a modern analog approach.

Apocrine secretion in the salivary glands of and other dipterans is evolutionarily conserved.

Apocrine secretion is a transport and secretory mechanism that remains only partially characterized, even though it is evolutionarily conserved among all metazoans, including humans. The excellent genetic model organism holds promise for elucidating the molecular mechanisms regulating this fundamental metazoan process. Two prerequisites for such investigations are to clearly define an experimental system to investigate apocrine secretion and to understand the evolutionarily and functional contexts in which apocrine secretion arose in that system.

Perspectives on Complex Care Training in a Large Academic Pediatric Training Program.

Objective: To identify gaps and opportunities in complex care training for pediatric residents.

Methods: Residents in an academic pediatric residency program were surveyed about: training experiences in complex care; self-entrustment in key clinical activities in complex care; educational strategies that would increase preparedness; and recommendations for curriculum development. We used descriptive statistics for quantitative data and content analysis for free-text responses.

The Unexpected Comfort of Feeling It All: A Support Group for Mothers of Autistic Adolescents Using the Lens of Ambiguous Loss.

Many parents experience grief and loss in response to their child receiving an autism diagnosis in early childhood. However, there is a dearth of research that considers if grief and loss are experienced by parents throughout their child's adolescence and young adulthood. Further, there is a small but growing body of evidence suggesting that parents of autistic children may be living with ambiguous loss in particular, that is, a loss for which there is no closure or resolution.

Quantitative Electroencephalography as a Biomarker for Cognitive Dysfunction in Parkinson's Disease.

Quantitative electroencephalography (qEEG) has been suggested as a biomarker for cognitive decline in Parkinson's disease (PD). Determine if applying a wavelet-based qEEG algorithm to 21-electrode, resting-state EEG recordings obtained in a routine clinical setting has utility for predicting cognitive impairment in PD. PD subjects, evaluated by disease stage and motor score, were compared to healthy controls ( = 20 each).

An apocrine mechanism delivers a fully immunocompetent exocrine secretion.

Apocrine secretion is a recently discovered widespread non-canonical and non-vesicular secretory mechanism whose regulation and purpose is only partly defined. Here, we demonstrate that apocrine secretion in the prepupal salivary glands (SGs) of Drosophila provides the sole source of immune-competent and defense-response proteins to the exuvial fluid that lies between the metamorphosing pupae and its pupal case. Genetic ablation of its delivery from the prepupal SGs to the exuvial fluid decreases the survival of pupae to microbial challenges, and the isolated apocrine secretion has strong antimicrobial effects in "agar-plate" tests.

Systemic delivery of a mitochondria targeted antioxidant partially preserves limb muscle mass and grip strength in response to androgen deprivation.

Muscle mass is important for health. Decreased testicular androgen production (hypogonadism) contributes to the loss of muscle mass, with loss of limb muscle being particularly debilitating. Androgen replacement is the only pharmacological treatment, which may not be feasible for everyone.

PROMIS Neuropathic and Nociceptive Pain Quality in Musculoskeletal Pain Presentations.

Objective: Musculoskeletal pain is a significant contributor to the global disease burden. Management of musculoskeletal pain where a neuropathic component is present can be challenging. This study evaluated the internal structure of the Patient-Reported Outcome Measures Information System (PROMIS) pain quality scales, explored the prevalence of neuropathic and nociceptive pain, and identified health demographics and behaviors related to musculoskeletal pain presentations.

Variable Effects of PD-Risk Associated SNPs and Variants in Parkinsonism-Associated Genes on Disease Phenotype in a Community-Based Cohort.

Genetic risk factors for Parkinson's disease (PD) risk and progression have been identified from genome-wide association studies (GWAS), as well as studies of familial forms of PD, implicating common variants at more than 90 loci and pathogenic or likely pathogenic variants at 16 loci. With the goal of understanding whether genetic variants at these PD-risk loci/genes differentially contribute to individual clinical phenotypic characteristics of PD, we used structured clinical documentation tools within the electronic medical record in an effort to provide a standardized and detailed clinical phenotypic characterization at the point of care in a cohort of 856 PD patients. We analyzed common SNPs identified in previous GWAS studies, as well as low-frequency and rare variants at parkinsonism-associated genes in the MDSgene database for their association with individual clinical characteristics and test scores at baseline assessment in our community-based PD patient cohort: age at onset, disease duration, Unified Parkinson's Disease Rating Scale I-VI, cognitive status, initial and baseline motor and non-motor symptoms, complications of levodopa therapy, comorbidities and family history of neurological disease with one or more than one affected family members.

Publisher Correction: A global database of Holocene paleotemperature records.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Olfactory Dysfunction in Familial and Sporadic Parkinson's Disease.

This minireview discusses our current understanding of the olfactory dysfunction that is frequently observed in sporadic and familial forms of Parkinson's disease and parkinsonian syndromes. We review the salient characteristics of olfactory dysfunction in these conditions, discussing its prevalence and characteristics, how neuronal processes and circuits are altered in Parkinson's disease, and what is assessed by clinically used measures of olfactory function. We highlight how studies of monogenic Parkinson's disease and investigations in ethnically diverse populations have contributed to understanding the mechanisms underlying olfactory dysfunction.