Proteo-genomics of soluble TREM2 in cerebrospinal fluid provides novel insights and identifies novel modulators for Alzheimer's disease.

Triggering receptor expressed on myeloid cells 2 (TREM2) plays a critical role in microglial activation, survival, and apoptosis, as well as in Alzheimer's disease (AD) pathogenesis. We previously reported the MS4A locus as a key modulator for soluble TREM2 (sTREM2) in cerebrospinal fluid (CSF). To identify additional novel genetic modifiers of sTREM2, we performed the largest genome-wide association study (GWAS) and identified four loci for CSF sTREM2 in 3,350 individuals of European ancestry.

A DUAL MTOR/NAD+ ACTING GEROTHERAPY.

The geroscience hypothesis states that a therapy that prevents the underlying aging process should prevent multiple aging related diseases. The mTOR (mechanistic target of rapamycin)/insulin and NAD+ (nicotinamide adenine dinucleotide) pathways are two of the most validated aging pathways. Yet, it's largely unclear how they might talk to each other in aging.

The Multifaceted Role of Autophagy in Endometrium Homeostasis and Disease.

Autophagy is a conserved fundamental cellular process with a primary function of catabolizing harmful or surplus cellular contents such as protein aggregates, dysfunctional/long-lived organelles, intracellular pathogens, and storage nutrients. An increasing body of evidence reveals that basal autophagy is essential for maintaining endometrial homeostasis and mediating endometrial-specific functions, including menstrual cycle, embryo implantation, and decidualization. However, perturbed levels of autophagy can lead to severe endometrial pathologies, including endometriosis, endometrial hyperplasia, endometrial cancer, adenomyosis, and leiomyoma.

TREM2 is a receptor for non-glycosylated mycolic acids of mycobacteria that limits anti-mycobacterial macrophage activation.

Mycobacterial cell-wall glycolipids elicit an anti-mycobacterial immune response via FcRγ-associated C-type lectin receptors, including Mincle, and caspase-recruitment domain family member 9 (CARD9). Additionally, mycobacteria harbor immuno-evasive cell-wall lipids associated with virulence and latency; however, a mechanism of action is unclear. Here, we show that the DAP12-associated triggering receptor expressed on myeloid cells 2 (TREM2) recognizes mycobacterial cell-wall mycolic acid (MA)-containing lipids and suggest a mechanism by which mycobacteria control host immunity via TREM2.

Moonshots for aging.

 As the global population ages, there is increased interest in living longer and improving one's quality of life in later years. However, studying aging - the decline in body function - is expensive and time-consuming. And despite research success to make model organisms live longer, there still aren't really any feasible solutions for delaying aging in humans.

Functional genomic analyses uncover APOE-mediated regulation of brain and cerebrospinal fluid beta-amyloid levels in Parkinson disease.

Alpha-synuclein is the main protein component of Lewy bodies, the pathological hallmark of Parkinson's disease. However, genetic modifiers of cerebrospinal fluid (CSF) alpha-synuclein levels remain unknown. The use of CSF levels of amyloid beta, total tau, and phosphorylated tau as quantitative traits in genetic studies have provided novel insights into Alzheimer's disease pathophysiology.

regulates the action of nitrogen-containing bisphosphonates on bone.

Nitrogen-containing bisphosphonates (N-BPs), such as alendronate, are the most widely prescribed medications for diseases involving bone, with nearly 200 million prescriptions written annually. Recently, widespread use of N-BPs has been challenged due to the risk of rare but traumatic side effects such as atypical femoral fracture (AFF) and osteonecrosis of the jaw (ONJ). N-BPs bind to and inhibit farnesyl diphosphate synthase, resulting in defects in protein prenylation.

A single-nuclei RNA sequencing study of Mendelian and sporadic AD in the human brain.

Background: Alzheimer's disease (AD) is the most common form of dementia. This neurodegenerative disorder is associated with neuronal death and gliosis heavily impacting the cerebral cortex. AD has a substantial but heterogeneous genetic component, presenting both Mendelian and complex genetic architectures.

The resident macrophages in murine pancreatic islets are constantly probing their local environment, capturing beta cell granules and blood particles.

Aims/hypothesis: We studied here the interactions between the resident macrophages of pancreatic islets with beta cells and the blood vasculature. We also examined the immunological consequences of such interactions.

Methods: Islets were isolated from C57BL/6 mice expressing CX3C motif chemokine receptor 1-green fluorescent protein (CX3CR-GFP) and examined live by two-photon microscopy.

Comparison of transforaminal lumbar interbody fusion outcomes in patients receiving rhBMP-2 versus autograft.

Background Context: Recombinant human bone morphogenetic protein 2 (rhBMP-2) plays a pivotal role in complex spine surgery. Despite its limited approval, the off-label use of rhBMP-2 is prevalent, particularly in transforaminal lumbar interbody fusions (TLIFs).

Purpose: To determine the effectiveness and safety of rhBMP-2 use in TLIF procedures versus autograft.

Equivalent Clinical Outcomes Following Favored Treatments of Chronic Scapholunate Ligament Tear.

Background: Optimal treatment of chronic scapholunate (SL) instability remains controversial. Many surgical techniques have been proposed with varied results in subsequent case series; however, there is limited evidence demonstrating the relative effectiveness of the different treatment options.

Questions/purposes: We conducted a systematic review of the English literature to compare outcomes from capsulodesis and ligament reconstruction for treatment of chronic scapholunate instability.

Attenuation Correction of PET/MR Imaging.

PET/MR is a promising multimodality imaging approach. Attenuation is by far the largest correction required for quantitative PET imaging. MR-based attenuation correction have been extensively pursued, especially for brain imaging, in the past several years.

Locking Plate Arthrodesis Compares Favorably with LRTI for Thumb Trapeziometacarpal Arthrosis: Early Outcomes from a Longitudinal Cohort Study.

Background: Trapeziometacarpal arthrodesis (TMA) has been complicated by nonunion and hardware failure.

Questions/purposes: We hypothesized that modification of the TMA technique with a locking cage plate construct would afford reliable bony union while producing greater hand function than trapeziectomy with ligament reconstruction and tendon interposition (LRTI) at early follow-up.

Methods: We enrolled 36 consecutive patients with trapeziometacapal osteoarthritis (14 TMA patients (15 thumbs), 22 LRTI patients (22 thumbs)).

New Radiographic Index for Occipito-Cervical Instability.

Study Design: Retrospective study.

Purpose: To propose a new radiographic index for occipito-cervical instability.

Overview Of Literature: Symptomatic atlanto-occipital instability requires the fusion of the atlanto-occipital joint.

Radiographic Comparison between Cervical Spine Lateral and Whole-Spine Lateral Standing Radiographs.

Study Design Retrospective radiologic study. Objective The sagittal alignment of the cervical spine can be evaluated using either a lateral cervical radiograph or a whole-spine lateral view on which the cervical spine is included. To our knowledge, however, no report has compared the two.

Hip Dysplasia in the Young Adult.

Hip dysplasia is a leading precursor of osteoarthritis and is seen in 20% to 40% of patients with osteoarthritis of the hip. An increase in mechanical stress on the cartilage matrix with failure of the acetabular labrum represents the major pathomechanism of degeneration. Because the prevalence of associated femoral deformities is high (>50%), the structural anatomy of the dysplastic hip must be assessed in multiple planes using radiographs and, if needed, advanced imaging modalities.

Role of ABCA7 loss-of-function variant in Alzheimer's disease: a replication study in European-Americans.

Introduction: A recent study found a significant increase of ABCA7 loss-of-function variants in Alzheimer's disease (AD) cases compared to controls. Some variants were located on noncoding regions, but it was demonstrated that they affect splicing. Here, we try to replicate the association between AD risk and ABCA7 loss-of-function variants at both the single-variant and gene level in a large and well-characterized European American dataset.

Surgical Anatomy of the Uncinate Process and Transverse Foramen Determined by Computed Tomography.

Study Design Computed tomography-based cohort study. Objective Although there are publications concerning the relationship between the vertebral artery and uncinate process, there is no practical guide detailing the dimensions of this region to use during decompression of the intervertebral foramen. The purpose of this study is to determine the anatomic parameters that can be used as a guide for thorough decompression of the intervertebral foramen.

Asymptomatic Stenosis in the Cervical and Thoracic Spines of Patients with Symptomatic Lumbar Stenosis.

Study Design Retrospective study. Objective Studies on age-related degenerative changes causing concurrent stenoses in the cervical, thoracic, and lumbar spines (triple stenosis) are rare in the literature. Our objectives were to determine: (1) the incidence of asymptomatic radiologic cervical and thoracic stenosis in elderly patients with symptomatic lumbar stenosis, (2) the incidence of concurrent radiologic spinal stenosis in the cervical and thoracic spines, and (3) the radiologic features of cervical stenosis that might predict concurrent thoracic stenosis.

Delayed surgical intervention in central cord syndrome with cervical stenosis.

Study Design Review of the literature. Objective It is generally accepted that surgical treatment is necessary for central cord syndrome (CCS) with an underlying cervical stenosis. However, the surgical timing for decompression is controversial in spondylotic cervical CCS.

Diagnostic value of oblique magnetic resonance images for evaluating cervical foraminal stenosis.

Background Context: The benefits of oblique magnetic resonance imaging (MRI) reformations to assess cervical neural foramina have been reported previously in clinical and cadaveric studies. But there is a paucity of literature investigating intra- and interobserver variabilities for assessing cervical foraminal stenosis using oblique MRI views.

Purpose: To determine the value of oblique MRI views compared with axial and sagittal views for assessing foraminal stenosis of the cervical spine using intra- and interobserver variabilities.

Early-onset metabolic syndrome in mice lacking the intestinal uric acid transporter SLC2A9.

Excess circulating uric acid, a product of hepatic glycolysis and purine metabolism, often accompanies metabolic syndrome. However, whether hyperuricaemia contributes to the development of metabolic syndrome or is merely a by-product of other processes that cause this disorder has not been resolved. In addition, how uric acid is cleared from the circulation is incompletely understood.

DHEA-mediated inhibition of the pentose phosphate pathway alters oocyte lipid metabolism in mice.

Women with polycystic ovary syndrome (PCOS) and hyperandrogenism have altered hormone levels and suffer from ovarian dysfunction leading to subfertility. We have attempted to generate a model of hyperandrogenism by feeding mice chow supplemented with dehydroepiandrosterone (DHEA), an androgen precursor that is often elevated in women with PCOS. Treated mice had polycystic ovaries, low ovulation rates, disrupted estrous cycles, and altered hormone levels.