Patient Language Does Not Impact Need for Manipulation Following Total Knee Arthroplasty.

Socioeconomic factors have been associated with an increased need for manipulation under anesthesia (MUA) following total knee arthroplasty (TKA). The purpose of this study was to compare the rate of MUA and range of motion (ROM) following primary TKA in English and non-English-speaking patients. The authors conducted a retrospective cohort study of all primary TKAs performed at their institution between 2010 and 2017.

Failure Following Revision Total Hip Arthroplasty After Cobalt-Chrome Femoral Heads are Placed on a Retained Femoral Stem.

Background: Failure due to trunnionosis with adverse local tissue reaction (ALTR) has been reported with cobalt-chrome (CoCr) heads in total hip arthroplasty (THA); however, there are limited data on the use of these heads in the revision setting. The purpose of this study was to analyze the outcomes of patients who underwent revision THA with a retained femoral component and received a CoCr femoral head on a used trunnion.

Methods: In this retrospective review, we identified all patients who underwent revision THA with a retained femoral component and received a CoCr femoral head between February 2006 and March 2014.

In vivo overexpression of synaptogyrin-3 promotes striatal synaptic dopamine uptake in LRRK2 mutant mouse model of Parkinson's disease.

Background: Leucine-rich repeat kinase 2 (LRRK2) mutation is a common genetic risk factor of Parkinson's disease (PD). Presynaptic dysfunction is an early pathogenic event associated with dopamine (DA) dysregulation in striatum of the brain. DA uptake activity of DA uptake transporter (DAT) affects synaptic plasticity and motor and non-motor behavior.

Using Downgaze Palsy Progression Rate to Model Survival in Progressive Supranuclear Palsy-Richardson Syndrome.

Background: Rapid development of downgaze palsy, the most specific symptom of progressive supranuclear palsy (PSP), has been associated with shorter survival in small studies.

Objective: We hypothesized that the progression rate of downgaze palsy and other disease features could predict survival if assessed soon after the onset of downgaze palsy in a large data set.

Methods: We used a longitudinal database of 414 patients with probable PSP-Richardson syndrome from 1994 to 2020.

Long-term inhibition of mutant LRRK2 hyper-kinase activity reduced mouse brain α-synuclein oligomers without adverse effects.

Parkinson's disease (PD) is characterized by dopaminergic neurodegeneration in nigrostriatal and cortical brain regions associated with pathogenic α-synuclein (αSyn) aggregate/oligomer accumulation. LRRK2 hyperactivity is a disease-modifying therapeutic target in PD. However, LRRK2 inhibition may be associated with peripheral effects, albeit with unclear clinical consequences.

Transcriptional Regulation of the Synaptic Vesicle Protein Synaptogyrin-3 () Gene: The Effects of NURR1 on Its Expression.

Synaptogyrin-3 (SYNGR3) is a synaptic vesicular membrane protein. Amongst four homologues (SYNGR1 to 4), SYNGR1 and 3 are especially abundant in the brain. SYNGR3 interacts with the dopamine transporter (DAT) to facilitate dopamine (DA) uptake and synaptic DA turnover in dopaminergic transmission.

LRRK2 mutant knock-in mouse models: therapeutic relevance in Parkinson's disease.

Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) are one of the most frequent genetic causes of both familial and sporadic Parkinson's disease (PD). Mounting evidence has demonstrated pathological similarities between LRRK2-associated PD (LRRK2-PD) and sporadic PD, suggesting that LRRK2 is a potential disease modulator and a therapeutic target in PD. LRRK2 mutant knock-in (KI) mouse models display subtle alterations in pathological aspects that mirror early-stage PD, including increased susceptibility of nigrostriatal neurotransmission, development of motor and non-motor symptoms, mitochondrial and autophagy-lysosomal defects and synucleinopathies.

LRRK2, GBA and their interaction in the regulation of autophagy: implications on therapeutics in Parkinson's disease.

Mutations in leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GBA) represent two most common genetic causes of Parkinson's disease (PD). Both genes are important in the autophagic-lysosomal pathway (ALP), defects of which are associated with α-synuclein (α-syn) accumulation. LRRK2 regulates macroautophagy via activation of the mitogen activated protein kinase/extracellular signal regulated protein kinase (MAPK/ERK) kinase (MEK) and the calcium-dependent adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathways.

High Expression of Nicotinamide N-Methyltransferase in Patients with Sporadic Alzheimer's Disease.

We have previously shown that the expression of nicotinamide N-methyltransferase (NNMT) is significantly increased in the brains of patients who have died of Parkinson's disease (PD). In this study, we have compared the expression of NNMT in post-mortem medial temporal lobe, hippocampus and cerebellum of 10 Alzheimer's disease (AD) and 9 non-disease control subjects using a combination of quantitative Western blotting, immunohistochemistry and dual-label confocal microscopy coupled with quantitative analysis of colocalisation. NNMT was detected as a single protein of 29 kDa in both AD and non-disease control brains, which was significantly increased in AD medial temporal lobe compared to non-disease controls (7.

Aberrant mitochondrial morphology and function associated with impaired mitophagy and DNM1L-MAPK/ERK signaling are found in aged mutant Parkinsonian LRRK2 mice.

Mitochondrial dysfunction causes energy deficiency and nigrostriatal neurodegeneration which is integral to the pathogenesis of Parkinson disease (PD). Clearance of defective mitochondria involves fission and ubiquitin-dependent degradation via mitophagy to maintain energy homeostasis. We hypothesize that LRRK2 (leucine-rich repeat kinase 2) mutation disrupts mitochondrial turnover causing accumulation of defective mitochondria in aging brain.

AMY1 Gene Copy Number Correlates With Glucose Absorption and Visceral Fat Volume, but Not with Insulin Resistance.

Background: The human amylase gene (AMY1) has a broad copy number (CN) variation that may associate with body mass index.

Methods: Deoxyribonucleic acid was extracted from urine (n = 74) and serum (n = 6) samples (Protein, Fiber and Metabolic Syndrome [ProFiMet] cohort), and buccal (n = 17) samples (Oral Starch Challenge [OSC] cohort), and assessed for AMY1 CN by droplet digital polymerase chain reaction. The association of AMY1 CN with comprehensive markers of metabolic status (ProFiMet cohort) were analyzed with Pearson's correlation coefficient (CC).

Nicotinamide -Methyltransferase: Genomic Connection to Disease.

Single-nucleotide polymorphisms (SNPs) in and around the nicotinamide -methyltransferase (NNMT) gene are associated with a range of cancers and other diseases and conditions. The data on these associations have been assembled, and their strength discussed. There is no evidence that the presence of either the major or minor base in any SNP affects the expression of nicotinamide -methyltransferase.

Nicotinamide N-methyltransferase expression in SH-SY5Y human neuroblastoma cells decreases oxidative stress.

Nicotinamide N-methyltransferase (NNMT) plays a central role in cellular metabolism, regulating pathways including epigenetic regulation, cell signalling, and energy production. Our previous studies have shown that the expression of NNMT in the human neuroblastoma cell line SH-SY5Y increased complex I activity and subsequent ATP synthesis. This increase in ATP synthesis was lower than the increase in complex I activity, suggesting uncoupling of the mitochondrial respiratory chain.

The interplay of aging, genetics and environmental factors in the pathogenesis of Parkinson's disease.

Background: Parkinson's disease (PD) is characterized by dopaminergic neuronal loss in the substantia nigra pars compacta and intracellular inclusions called Lewy bodies (LB). During the course of disease, misfolded α-synuclein, the major constituent of LB, spreads to different regions of the brain in a prion-like fashion, giving rise to successive non-motor and motor symptoms. Etiology is likely multifactorial, and involves interplay among aging, genetic susceptibility and environmental factors.

Age-dependent accumulation of oligomeric SNCA/α-synuclein from impaired degradation in mutant LRRK2 knockin mouse model of Parkinson disease: role for therapeutic activation of chaperone-mediated autophagy (CMA).

Parkinson disease (PD) is an age-related neurodegenerative disorder associated with misfolded SNCA/α-synuclein accumulation in brain. Impaired catabolism of SNCA potentiates formation of its toxic oligomers. (leucine-rich repeat kinase-2) mutations predispose to familial and sporadic PD.

Human amylase gene copy number variation as a determinant of metabolic state.

Introduction: Humans have multiple genes encoding amylase that are broadly divided into salivary (AMY1) and pancreatic (AMY2) genes. They exhibit some of the greatest copy numbers of any human gene, an expansion possibly driven by increased dietary starch intake. Within the population, amylase gene copy number is highly variable and there is evidence of an inverse association between AMY1 copy number and BMI.

The kinetic analysis of the N-methylation of 4-phenylpyridine by nicotinamide N-methyltransferase: Evidence for a novel mechanism of substrate inhibition.

The N-methylation of 4-phenylpyridine produces the neurotoxin 1-methyl-4-phenylpyridinium ion (MPP+). We investigated the kinetics of 4-phenylpyridine N-methylation by nicotinamide N-methyltransferase (NNMT) and its effect upon 4-phenylpyridine toxicity in vitro. Human recombinant NNMT possessed 4-phenylpyridine N-methyltransferase activity, with a specific activity of 1.

The Clinical Utility of Measuring IgG Subclass Immunoglobulins During Immunological Investigation for Suspected Primary Antibody Deficiencies.

Measurement of IgG subclass concentrations is a standard laboratory test run as part of a panel to investigate the suspicion of antibody deficiency. The assessment is clinically important when total IgG is within the normal age-specific reference range. The measurement is useful for diagnosis of IgG subclass deficiency, to aid the diagnosis of specific antibody deficiency, as a supporting test for the diagnosis of common variable immunodeficiency, as well as for risk stratification of patients with low IgA.

Serum IgG4 Concentration in IgG4-Related Disease.

Background: IgG4-related disease (IgG4-RD) is an immune-mediated and chronic fibroinflammatory condition that affects almost any organ and often involves multiple organs in the same patient. In this review article, we address the clinical utility of measuring serum immunoglobulin G subclass 4 concentration ([IgG4]) in IgG4-RD diagnosis and in disease monitoring.

Methods: We discuss the latest literature on the relevance of [IgG4] to the investigation and management of IgG4RDs.

Nicotinamide -Methyltransferase in Health and Cancer.

Over the past decade, the roles of nicotinamide -methyltransferase and its product 1-methyl nicotinamide have emerged from playing merely minor roles in phase 2 xenobiotic metabolism as actors in some of the most important scenes of human life. In this review, the structures of the gene, messenger RNA, and protein are discussed, together with the role of the enzyme in many of the common cancers that afflict people today.

Combined LRRK2 mutation, aging and chronic low dose oral rotenone as a model of Parkinson's disease.

Aging, genetics and environmental toxicity are important etiological factors in Parkinson's disease (PD). However, its pathogenesis remains unclear. A major obstacle is the lack of an appropriate experimental model which incorporates genetic susceptibility, aging and prolonged environmental toxicity.

Nicotinamide N-methyltransferase catalyses the N-methylation of the endogenous β-carboline norharman: evidence for a novel detoxification pathway.

Nicotinamide N-methyltransferase (NNMT) is responsible for the N-methylation of nicotinamide to 1-methylnicotinamide. Our recent studies have demonstrated that NNMT regulates cellular processes fundamental to the correct functioning and survival of the cell. It has been proposed that NNMT may possess β-carboline (BC) N-methyltransferase activity, endogenously and exogenously produced pyridine-containing compounds which, when N-methylated, are potent inhibitors of Complex I and have been proposed to have a role in the pathogenesis of Parkinson's disease.