Linking Stage-Specific Plasma Biomarkers to Gray Matter Atrophy in Parkinson Disease.

BACKGROUND AND PURPOSE: The shortcomings of synucleinopathy-based Parkinson disease staging highlight the need for systematic clinicopathologic elucidation and biomarkers. In this study, we investigated associations of proteinopathy and inflammation markers with changes in gray matter volume that accompany Parkinson disease progression. MATERIALS AND METHODS: We prospectively enrolled 42 patients with idiopathic Parkinson disease, subdivided into early-/late-stage groups and 27 healthy controls. Parkinson disease severity and participants' functional and cognitive performance were evaluated. Peripheral plasma α-synuclein, ß-amyloid42, and tau were quantified with immunomagnetic reduction assays, and nuclear DNA by polymerase chain reaction, and regional gray matter volumes were determined by MR imaging. Statistical tests identified stage-specific biomarkers and gray matter volume patterns in the early-stage Parkinson disease, late-stage Parkinson disease, and control groups. Correlations between gray matter volume atrophy, plasma biomarkers, Parkinson disease severity, and cognitive performance were analyzed. RESULTS: Patients with Parkinson disease had significantly elevated α-synuclein, tau, and ß-amyloid42 levels compared with controls; nuclear DNA levels were similar in early-stage Parkinson disease and controls, but higher in late-stage Parkinson disease (all P < .01). We identified 3 stage-specific gray matter volume atrophy patterns: 1) control > early-stage Parkinson disease = late-stage Parkinson disease: right midfrontal, left lingual, and fusiform gyri, left hippocampus, and cerebellum; 2) control > early-stage Parkinson disease > late-stage Parkinson disease: precentral, postcentral, parahippocampal, left superior-temporal, right temporal, right superior-frontal, and left cingulate gyri, occipital lobe, and bilateral parts of the cerebellum; 3) control = early-stage Parkinson disease > late-stage Parkinson disease: left midfrontal, superior-frontal and temporal, amygdala, and posterior cingulate gyri, caudate nucleus, and putamen. We discovered stage-specific correlations among proteinopathy, inflammation makers, topographic gray matter volume patterns, and cognitive performance that accompanied Parkinson disease progression. CONCLUSIONS: Identifying associations linking peripheral plasma biomarkers, gray matter volume, and clinical status in Parkinson disease may facilitate earlier diagnosis and improve prognostic accuracy.

Intervention versus Aggressive Medical Therapy for Cognition in Severe Asymptomatic Carotid Stenosis.

BACKGROUND AND PURPOSE: Asymptomatic carotid stenosis of ≥70% increases the incidence of microembolism and/or chronic hypoperfusion, which may consequently impair neurocognition and brain connections. We sought controlled evidence for any cognitive benefit of aggressive medical therapy and combined carotid revascularization. MATERIALS AND METHODS: Patients with asymptomatic, unilateral, ≧70% stenosis of the extracranial ICA chose either aggressive medical therapy alone or in combination with carotid artery stent placement in this nonrandomized controlled study. They were examined with a battery of neuropsychological tests, structural MR imaging, DTI, and resting-state fMRI before and 3 months after treatment. RESULTS: Forty patients were included with 15 in the medical group and 25 in the stent-placement group. Among them, 13 and 21 in the respective groups completed neuroimaging follow-up. The baseline characteristics and the changes in cognitive performance during 3 months showed no differences between treatment groups. Nevertheless, compared with the medical group, the stent-placement group showed subjective dizziness alleviation (P = .045) and a small increase in fractional anisotropy at the splenium of the corpus callosum and the posterior periventricular white matter ipsilateral to carotid artery stent placement. Moreover, only the stent-placement group showed interval improvement in immediate memory and visuospatial performance, which was accompanied by an increase of functional connectivity at the insular cortex of the dorsal attention network and the medial prefrontal cortex of the default mode network. CONCLUSIONS: Both aggressive medical therapy alone and combined carotid revascularization in ≧70% asymptomatic carotid stenosis similarly preserved cognition during 3-month follow-up, though the latter had the potential for dizziness alleviation and cognitive and connectivity enhancement.

Significant volume reduction and shape abnormalities of the basal ganglia in cases of chronic liver cirrhosis.

BACKGROUND AND PURPOSE: Chronic liver disease frequently includes cognitive and movement disorders, suggesting an alteration of the striatum. With the exception of hyperintensities evident on T1-weighted images indicative of Mn deposition, radiographic findings of the BG are nonspecific. Volumetric and morphometric analysis of DGM is limited. Whether DGM undergoes degeneration and whether this change is associated with pallidal hyperintensity and cognitive performance are currently unknown in patients with cirrhosis. MATERIALS AND METHODS: The DGM volumes of 28 patients with chronic cirrhosis and 28 control patients were compared. Using 3D high-resolution MR images, the volume and shape of each structure were automatically analyzed by the FSL. Correlations between the DGM volume and other clinical variables, including the pallidal signal intensity, were assessed by multiple regression analysis. RESULTS: Patients with Child B and Child C liver disease had significantly smaller bilateral putaminal volumes than control patients, and patients with Child C also demonstrated smaller left caudate nucleus and left amygdala volumes than control patients. Pallidal hyperintensity correlated with smaller striatum volume, which was linearly related to worse cognitive performance. The nonuniform distributed shape abnormalities in the striatum further support the ascending spiral interconnecting theory of the striatum. CONCLUSIONS: These findings strongly suggest lower DGM volume develops according to the severity of the liver cirrhosis. The Mn deposition might contribute the striatum deficit. These findings support the value of additional psychomotor research associated with liver cirrhosis.

Sex differences in the neuroanatomy of human mirror-neuron system: a voxel-based morphometric investigation.

Females frequently perform better in empathy, interpersonal sensitivity, and emotional recognition than do males. The mirror-neuron system has been proposed to play an important role in social cognition. It remains to be clarified, however, whether the neuroanatomy underlying the human mirror neuron system exhibits sex differences. With the use of voxel-based morphometry analysis, a whole-brain unbiased technique to characterize regional cerebral volume differences in structural magnetic resonance images, concurrent with the dispositional empathy measures, we demonstrate that young adult females (n=25) had significantly larger gray matter volume in the pars opercularis and inferior parietal lobule than matched males (n=25) participants. Moreover, higher self-report scores in the emotional empathic disposition was tightly coupled with larger gray matter volume of the pars opercularis across all female and male participants (P=0.002). These results indicate that the existence of neuroanatomical sex differences in the human mirror-neuron system. They also suggest that the network of the human mirror-neuron system is strongly linked to empathy competence.

Caffeine content of prepackaged national-brand and private-label carbonated beverages.

Caffeine is a well-known stimulant that is added as an ingredient to various carbonated soft drinks. Due to its stimulatory and other physiological effects, individuals desire to know the exact amount of caffeine consumed from these beverages. This study analyzed the caffeine contents of 56 national-brand and 75 private-label store-brand carbonated beverages using high-performance liquid chromatography. Caffeine contents ranged from 4.9 mg/12 oz (IGA Cola) to 74 mg/12 oz (Vault Zero). Some of the more common national-brand carbonated beverages analyzed in this study with their caffeine contents were Coca-Cola (33.9 mg/12 oz), Diet Coke (46.3 mg/12 oz), Pepsi (38.9 mg/12 oz), Diet Pepsi (36.7 mg/12 oz), Dr Pepper (42.6 mg/12 oz), Diet Dr Pepper (44.1 mg/12 oz), Mountain Dew (54.8 mg/12 oz), and Diet Mountain Dew (55.2 mg/12 oz). The Wal-Mart store-brand beverages with their caffeine contents were Sam's Cola (12.7 mg/12 oz), Sam's Diet Cola (13.3 mg/12 oz), Dr Thunder (30.6 mg/12 oz), Diet Dr Thunder (29.9 mg/12 oz), and Mountain Lightning (46.5 mg/12 oz). Beverages from 14 other stores were also analyzed. Most store-brand carbonated beverages were found to contain less caffeine than their national-brand counterparts. The wide range of caffeine contents in carbonated beverages indicates that consumers would benefit from the placement of caffeine values on food labels.

Suture anchor repair of ulnar-sided triangular fibrocartilage complex tears.

Traditional open repair of traumatic triangular fibrocartilage complex (TFCC) tears requires a relatively extensive exposure, and arthroscopic repair, though conceptually simple, can be technically demanding. We describe a mini-open suture anchor technique that, while minimally invasive, is easier to perform than previously described open or arthroscopic techniques. Results achieved using this technique in eight cases compare favourably with those reported for other techniques.

Clinical, metabolic and endocrine parameters in response to metformin in obese women with polycystic ovary syndrome: a randomized, double-blind and placebo-controlled trial.

There is still some controversy concerning the effects of metformin in the treatment of Polycystic Ovary Syndrome (PCOS). The aim of this study was to asses the effect of metformin on clinical, metabolic and hormone parameters in obese women with PCOS. Thirty obese, non-diabetic women with PCOS received 500 mg of metformin or placebo, TID, over 90 days. Assessed parameters included body mass index, waist-to-hip ratio, blood pressure, FSH, LH, total testosterone, SHBG, fasting insulinemia, insulin-to-glucose ratio, total, HDL and LDL cholesterol, triglycerides, and menstrual cycles before and after the use of the drugs. Before treatment, patients did not differ in the two groups. After 90 days of metformin use, PCOS women presented significantly lower levels of total testosterone (p = 0.030) and total cholesterol (p = 0.023) compared to the women that used placebo. The other parameters did not differ between the groups. In conclusion, obese women with PCOS may benefit from the use of metformin through the reduction of hyperandrogenemia, total cholesterol, and possibly by restoration of regular menstrual cycles. Further studies with longer follow-ups are necessary to determine cardiovascular and endometrial metformin benefits and insulin-resistance decrease in women with polycystic ovary syndrome.

Bony tissue repair.

Bone is among the most frequently injured of tissues, and bony injuries are among the conditions most commonly treated by hand therapists. An understanding of the biology of bony tissue repair, as well as the techniques available for its promotion, is therefore of the utmost importance to practitioners of hand therapy. This article addresses the biology of bony tissue repair, techniques currently available for the treatment of bony injuries, and management of specific bony injuries of the hand.

Subcellular fractionation of rat sciatic nerve and specific localization of ganglioside LM1 in rat nerve myelin.

Subcellular fractionation of rat sciatic nerve was developed to determine the specific localization of gangliosides in the nerve membrane fractions. Myelin, microsomal, and a plasma membrane-like fraction were isolated and purified by sucrose density gradient centrifugation. These subfractions were characterized by electron microscopy, marker enzyme assays, and their protein and lipid profile. In rat sciatic nerve myelin, 90 mol% of the total gangliosides were monosialogangliosides. LM1 (sialosyl-lactoneotetraosylceramide) (61 mol%) and GM3 (21%) were the major gangliosides of the rat nerve myelin. Two other neolacto series of gangliosides, viz., sialosyl-lactoneonorhexaosylceramide and sialosyl-lactoneooctaosylceramide, were also localized mostly in the myelin fraction. GM1 was only a minor (less than 2%) ganglioside in myelin. The ganglioside patterns of the microsomal and plasma membrane-like fractions were similar with minor quantitative differences and were entirely different from that of myelin. Monosialogangliosides were approximately 70-75 mol% of the total in these fractions. The major gangliosides of the microsomal and plasma membrane-like fractions were GM3 (approximately 40%) and GM1 (approximately 20%). LM1 in these fractions was minimal (less than approximately 5%). Significant amounts of GM3 with N-glycolylneuraminic acid (approximately 10%) and GM1b (4-14%) were also identified in the microsomal and plasma membrane-like fractions but not in myelin. These and the higher lactoneo series of gangliosides have not been previously reported to be present in the rat nervous system. Almost exclusive localization of LM1 in myelin in rat peripheral nervous system is consistent with our previous observation that deposition of LM1 in the nerve with age was very similar to that of myelin marker lipids cerebrosides and sulfatides.

Structure of a glycolipid reacting with monoclonal IgM in neuropathy and with HNK-1.

An acidic glycolipid antigen that reacts with monoclonal IgM in patients with demyelinating neuropathy and with the mouse monoclonal antibody, HNK-1, was purified from human peripheral nerves. This lipid sharing antigenic determinants with the myelin-associated glycoprotein was shown to be an unusual glucuronic acid-containing sulfated glycosphingolipid with five sugars, but without sialic acid. Mild acid methanolysis converted the GlcUA to its methyl ester, removed the acidic sulfate group and abolished the antigenicity. Results from chemical, enzymatic, infrared, and mass spectral analysis suggested the following structure with a sulfate in a position that remains to be determined: GlcUA beta 1----3Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4Glc beta 1----1 ceramide.

Neutral glycosphingolipids and ceramide composition of ethylnitrosourea-induced rat neural tumors: accumulation of ceramide in tumors.

Experimental rat neural tumors in offspring were induced transplacentally by a single injection of a chemical carcinogen, ethylnitrosourea, 20 mg/kg body weight, in the tail vein of the mother. The neutral glycosphingolipid, sulfatide, and ceramide composition of the tumors and the normal tissues from which the tumors originated is described. The content of nonhydroxy fatty acid (NFA) and hydroxy fatty acid (HFA) containing ceramide in all the neural tumors so far examined was significantly increased compared with the corresponding normal neural tissue. Some 8 to 18 mol% of total neutral glycolipids was as ceramide in neurinomas, oligodendrogliomas, and meningiomas. Lactosylceramide in normal neural tissues was about 1 mol% of the total neutral glycosphingolipids. In various neural tumors lactosylceramide increased up to 8 mol%. NFA- and HFA-containing cerebrosides constitute 94-100% of the neutral glycosphingolipids in normal neural tissues. In various neural tumors the mol percent of cerebrosides was significantly reduced. A high performance liquid chromatographic method was modified to analyze simultaneously ceramides, cerebrosides, and higher neutral glycosphingolipids.

UDP-galactose-ceramide galactosyltransferase in rat brain myelin subfractions during development.

The localization and activity of the enzyme UDP-galactose-hydroxy fatty acid-containing ceramide galactosyltransferase is described in rat brain myelin subfractions during development. Other lipid-synthesizing enzymes, such as cerebroside sulphotransferase, UDP-glucose-ceramide glucosyltransferase and CDP-choline-1,2-diacylglycerol cholinephosphotransferase, were also studied for comparison in myelin subfractions and microsomal membranes. The purified myelin was subfractionated by isopycnic sucrose-density-gradient centrifugation. Four myelin subfractions, three floating respectively on 0.55 M- (light-myelin fraction), 0.75 M- (heavy-myelin fraction) and 0.85 M-sucrose (membrane fraction), and a pellet, were isolated and purified. At all ages, 70--75% of the total myelin proteins was found in the heavy-myelin fraction, whereas 2--5% of the protein was recovered in the light-myelin fraction, and about 7--12% in the membrane fraction. Most of the galactosyltransferase was associated with the heavy-myelin and membrane fractions. Other lipid-synthesizing enzymes studied appeared not to associate with purified myelin or myelin subfractions, but were enriched in the microsomal-membrane fraction. During development, the specific activity of the microsomal galactosyltransferase reached a maximum when the animals were about 20 days old and then declined. By contrast the specific activity of the galactosyltransferase in the heavy-myelin and membrane fractions was 3--4 times higher than that of the microsomal membranes in 16-day-old animals. The specific activity of the enzyme in the heavy-myelin fraction sharply declined with age. Chemical and enzymic analyses of the heavy-myelin and membrane myelin subfractions at various ages showed that the membrane fraction contained more proteins in relation to lipids than the heavy-myelin fraction. The membrane fraction was also enriched in phospholipids compared with cholesterol and contrined equivalent amounts of 2':3'-cyclic nucleotide 3'-phosphohydrolase compared with heavy- and light-myelin fractions. The membrane fraction was deficient in myelin basic protein and proteolipid protein and enriched in high-molecular-weight proteins. The specific localization of galactosyltransferase in heavy-myelin and membrane fractions at an early age when myelination is just beginning suggests that it may have some role in the myelination process.

Glutamate dehydrogenase from pumpkin cotyledons: characterization and isoenzymes.

Glutamate dehydrogenase from pumpkin (Cucurbita moschata Pior. cultivar Dickinson Field) cotyledons was found in both soluble and particulate fractions with the bulk of the activity in the soluble fraction. Both enzymes used NAD(H) and NADP(H) but NAD(H) was favored. The enzymes were classified as glutamate-NAD oxidoreductase, deaminating (EC 1.4.1.3). Both enzymes were heat stable, had a pH optimum for reductive amination of 8.0, and were inhibited by high concentrations of NH(4) (+) or alpha-ketoglutarate. The soluble enzyme was more sensitive to NH(4) (+) inhibition and was activated by metal ions after ammonium sulfate fractionation while the solubilized particulate enzyme was not. Inhibition by ethylenediaminetetraacetate was restored by several divalent ions and inhibition by p-hydroxymercuribenzoate was reversed by glutathione. Particulate glutamate dehydrogenase showed a greater activity with NADP. The molecular weights of the enzymes are 250,000. Separation of the enzymes by disc gel electrophoresis showed that during germination the soluble isoenzymes increased from 1 to 7 in number, while only one particulate isoenzyme was found at any time. This particulate isoenzyme was identical with one of the soluble isoenzymes. A number of methods indicated that the soluble isoenzymes were not simply removed from the particulate fraction and that true isoenzymes were found.