Different effects of fatty acid oxidation on hematopoietic stem cells based on age and diet.

Fatty acid oxidation is of uncertain importance in most stem cells. We show by C-palmitate tracing and metabolomic analysis that hematopoietic stem/progenitor cells (HSPCs) engage in long-chain fatty acid oxidation that depends upon carnitine palmitoyltransferase 1a (CPT1a) and hydroxyacyl-CoA dehydrogenase (HADHA) enzymes. CPT1a or HADHA deficiency had little or no effect on HSPCs or hematopoiesis in young adult mice.

Intrinsic link between PGRN and Gba1 D409V mutation dosage in potentiating Gaucher disease.

Gaucher disease (GD) is caused by biallelic GBA1/Gba1 mutations that encode defective glucocerebrosidase (GCase). Progranulin (PGRN, encoded by GRN/Grn) is a modifier of GCase, but the interplay between PGRN and GCase, specifically GBA1/Gba1 mutations, contributing to GD severity is unclear. Mouse models were developed with various dosages of Gba1 D409V mutation against the PGRN deficiency (Grn-/-) [Grn-/-;Gba1D409V/WT (PG9Vwt), Grn-/-;Gba1D409V/D409V (PG9V), Grn-/-;Gba1D409V/Null (PG9VN)].

Open Ankle Fractures in Older Individuals: A Multi-center Study.

The purpose of this study is to identify demographics, etiology, comorbidities, treatment, complications, and outcomes for older patients with open ankle fractures. Patients ≥60 years old who sustained an open ankle fracture between January 1, 2004 and March 31, 2014 at 6 Level 1 trauma centers were retrospectively reviewed. Univariate analysis using chi-squared or Student's t test was performed to identify associations between preoperative variables and 2 postoperative outcomes of interest: amputation and 1-year mortality.

The Effects of Blood Glucose Control in the Operative Spine Patient: A Systematic Review.

Objective: To our knowledge, this is the first systematic review to evaluate the available literature on the effects of perioperative serum glucose (SG) on outcomes for patients undergoing spine surgery. This review will add insight into how the perioperative management of SG affects the outcomes of patients undergoing spine surgery.

Methods: Three databases were used in this review including Embase, PubMed, and Cochrane Library.

Environmentally relevant atrazine exposure leads to increases in DNA damage and changes in morphology in the hepatopancreas of crayfish ().

The herbicide atrazine is widely used for controlling broad leaf weeds and increasing crop yields in agricultural areas. Atrazine enters aquatic environments through runoff, ground water discharge and seepage where concentrations have been recorded above 300 ppb. Exposure to the herbicide atrazine at environmentally relevant concentrations has been shown to negatively impact aquatic organisms, including crayfish.

PGRN deficiency exacerbates, whereas a brain penetrant PGRN derivative protects, mutation-associated pathologies and diseases.

Mutations in , encoding glucocerebrosidase (GCase), cause Gaucher disease (GD) and are also genetic risks in developing Parkinson's disease (PD). Currently, the approved therapies are only effective for directly treating visceral symptoms, but not for primary neuronopathic involvement in GD (nGD). Progranulin (PGRN), encoded by , is a novel modifier of GCase, but the impact of PGRN in mutation-associated pathologies in vivo remains unknown.

Lateral Lumbar Interbody Fusion at the L5-S1 Vertebral Level: A Unique Anatomical Case Report.

A 57-year-old female presented with L4-L5 and L5-S1 mobile spondylolisthesis and associated stenosis with radiculopathy who failed conservative treatment. This patient underwent lateral lumbar interbody fusion (LLIF) of L4-L5 and L5-S1, and posterior spinal fusion (PSF) with instrumentation. LLIF is a minimally invasive procedure to treat degenerative diseases of the lumbar spine.

Screening, patient identification, evaluation, and treatment in patients with Gaucher disease: Results from a Delphi consensus.

Several guidelines are available for identification and management of patients with Gaucher disease, but the most recent guideline was published in 2013. Since then, there have been significant advances in newborn screening, phenotypic characterization, identification of biomarkers and their integration into clinical practice, and the development and approval of new treatment options. Accordingly, the goal of this Delphi consensus exercise was to extend prior initiatives of this type by addressing issues related to newborn screening, diagnostic evaluations, and treatment (both disease directed and adjunctive).

C-X-C Motif Chemokine Ligand 9 and Its CXCR3 Receptor Are the Salt and Pepper for T Cells Trafficking in a Mouse Model of Gaucher Disease.

Gaucher disease is a lysosomal storage disease, which happens due to mutations in / that encodes the enzyme termed as lysosomal acid β-glucosidase. The major function of this enzyme is to catalyze glucosylceramide (GC) into glucose and ceramide. The deficiency of this enzyme and resultant abnormal accumulation of GC cause altered function of several of the innate and adaptive immune cells.

Substrate Reduction Therapy Reverses Mitochondrial, mTOR, and Autophagy Alterations in a Cell Model of Gaucher Disease.

Substrate reduction therapy (SRT) in clinic adequately manages the visceral manifestations in Gaucher disease (GD) but has no direct effect on brain disease. To understand the molecular basis of SRT in GD treatment, we evaluated the efficacy and underlying mechanism of SRT in an immortalized neuronal cell line derived from a knockout () mouse model. neurons accumulated substrates, glucosylceramide, and glucosylsphingosine.

More Than One-third of Orthopaedic Applicants Are in the Top 10%: The Standardized Letter of Recommendation and Evaluation of Orthopaedic Resident Applicants.

Background: The American Orthopaedic Association (AOA) released the standardized letter of recommendation (SLOR) form to provide standardized information to evaluators of orthopaedic residency applicants. The SLOR associates numerical data to an applicant's letter of recommendation. However, it remains unclear whether the new letter form effectively distinguishes among orthopaedic applicants, for whom letters are perceived to suffer from "grade inflation.

Resident Wellness During the COVID-19 Pandemic: A Nationwide Survey of Orthopaedic Residents.

Introduction: The COVID-19 pandemic has influenced the resident workforce to a particularly powerful and unexpected extent. Given the drastic changes to resident roles, expectations, and responsibilities, many valuable lessons regarding resident concerns and wellness can be garnered from this unique experience.

Methods: A voluntary survey was sent to 179 Accreditation Council for Graduate Medical Education-accredited orthopaedic surgery residency program directors to distribute to their residents.

Systemic enzyme delivery by blood-brain barrier-penetrating SapC-DOPS nanovesicles for treatment of neuronopathic Gaucher disease.

Background: Enzyme replacement therapy (ERT) can positively affect the visceral manifestations of lysosomal storage diseases (LSDs). However, the exclusion of the intravenous ERT agents from the central nervous system (CNS) prevents direct therapeutic effects.

Methods: Using a neuronopathic Gaucher disease (nGD) mouse model, CNS-ERT was created using a systemic, non-invasive, and CNS-selective delivery system based on nanovesicles of saposin C (SapC) and dioleoylphosphatidylserine (DOPS) to deliver to CNS cells and tissues the corrective, functional acid β-glucosidase (GCase).

The Influence of Thermal Residual Stresses on Mechanical Properties of Silicon Nitride-Based Composites.

In this work, two kinds of silicon nitride-based composites, namely, those with titanium nitride or silicon carbide additives, were sintered using the hot pressing technique (HP). The phase composition, microstructure, and mechanical and elastic properties of the materials were characterized. Three-dimensional geometric models of the composites were created on the basis of microstructure parameters.

Keloid and Hypertrophic Scar Formation, Prevention, and Management: Standard Review of Abnormal Scarring in Orthopaedic Surgery.

Keloid and hypertrophic scar formation after orthopaedic surgical closure is a complex issue. The nature and location of procedures maximize wound tension, leave foreign bodies, and diminish dermal supply, all potentiating keloid formation. There is little discussion regarding the pathophysiology and management of this recurrent problem in orthopaedic literature.

Epidural Abscess Caused by Gas-Producing Clostridium Septicum: A Case Report.

Case: Few cases have reported Clostridium species of bacteria as a source for vertebral osteomyelitis and epidural abscesses. The subspecies of Clostridium septicum has not been described as a cause. This case describes a 69-year-old man who hematogenously spread C.

The Haitian Orthopaedic Residency Exchange Program.

Unlabelled: After a devastating earthquake in Haiti in 2010, multiple South Carolinian orthopaedic teams, funded by the South Carolina Orthopedic Association (SCOA), developed an exchange program for Haitian residents.

Methods: SCOA teams have sequentially logged their patient experiences since 2015 for a total of six updates per year. These logs were reviewed in detail to evaluate clinical results in terms of case volumes, cases performed, follow-up obtained, and complications.

Intravenous infusion of iPSC-derived neural precursor cells increases acid β-glucosidase function in the brain and lessens the neuronopathic phenotype in a mouse model of Gaucher disease.

Gaucher disease (GD) is caused by GBA1 mutations leading to functional deficiency of acid-β-glucosidase (GCase). No effective treatment is available for neuronopathic GD (nGD). A subclass of neural stem and precursor cells (NPCs) expresses VLA4 (integrin α4β1, very late antigen-4) that facilitates NPC entry into the brain following intravenous (IV) infusion.

Combination of acid β-glucosidase mutation and Saposin C deficiency in mice reveals Gba1 mutation dependent and tissue-specific disease phenotype.

Gaucher disease is caused by mutations in GBA1 encoding acid β-glucosidase (GCase). Saposin C enhances GCase activity and protects GCase from intracellular proteolysis. Structure simulations indicated that the mutant GCases, N370S (0 S), V394L (4L) and D409V(9V)/H(9H), had altered function.