Statin use reduces the risk of dementia in elderly patients: a nationwide data survey and propensity analysis.

OBJECTIVES: The objective of this study was to examine the association between the use of statins and the risk of newly diagnosed dementia in an elderly population. DESIGN, SETTING AND PARTICIPANTS: Random samples of 1,000,000 individuals covered by the National Health Insurance in Taiwan were included in the analysis. All participants were 65 years or older without dementia and either did or did not start treatment with statins from 1 August 1997 to 31 December 2010. Patients with established dementia before the start of treatment were excluded. Baseline characteristics were matched (by propensity score) in those who did and did not receive statins. RESULTS: A total of 57,669 subjects were included in the analysis with approximately 12 years of follow-up. Propensity score matching identified 2003 patients who received statins and another 2003 patients who did not with comparable baseline characteristics. Adjusted hazard ratios (HRs) for dementia were significantly inversely associated with total or daily equivalent statin dosage (total accumulated dose: HRs 0.829, 0.720 and 0.385 from T1 to T3 vs. control, P < 0.001 for trend; mean daily dose: HRs 0.667, 0.798 and 0.503 from T1 to T3 vs. control, P < 0.001). The results remained robust after propensity adjustment. CONCLUSION: Independent of traditional risk factors, there was a decrease in newly diagnosed cases of dementia in elderly patients who had received a high total or daily dose of statins. The more potent statins (e.g. atorvastatin and rosuvastatin) seemed to be particularly effective in the prevention of dementia.

Osteoprotegerin, inflammation and dyslipidemia are associated with abdominal aortic calcification in non-diabetic patients on peritoneal dialysis.

BACKGROUND AND AIMS: Abdominal aortic calcification (AC) has been reported to be associated with cardiovascular disease (CVD) in hemodialysis patients but is rarely discussed in peritoneal dialysis (PD) patients. We examined the independent predictors and predictive power for survival of AC in prevalent PD patients. METHODS AND RESULTS: AC was detected by computed tomography (CT) and represented as the percentage of the total aortic cross-section area affected by AC (%AC). The predictors of %AC ≥ 15 were examined by multiple logistic regression analysis. Cox proportional hazard analysis was used to determine the hazard ratios associated with high %AC. A total of 183 PD patients were recruited to receive CT scans and divided into group 1 (%AC < 15, n = 97), group 2 (%AC ≥ 15, n = 41), and group 3 (diabetic patients, n = 45). Group 1 patients had lower osteoprotegerin (OPG) levels than group 2 patients (798 ± 378 vs. 1308 ± 1350 pg/mL, p < 0.05). The independent predictors for %AC ≥ 15 included the atherogenic index, OPG, and C-reactive protein (CRP). The age-adjusted hazard ratios associated with %AC ≥ 15 were 3.46 (p = 0.043) for mortality and 1.90 (p = 0.007) for hospitalization. CONCLUSIONS: %AC can predict mortality and morbidity in non-diabetic PD patients, and 15% is a good cut-off value for such predictions. There are complex associations among mineral metabolism, inflammation, and dyslipidemia in the pathogenesis of AC.

A functional variant in the promoter region regulates the C-reactive protein gene and is a potential candidate for increased risk of atrial fibrillation.

OBJECTIVES: In a large population-based cohort, the level of C-reactive protein (CRP) in patients at baseline predicts an increased risk of future development of atrial fibrillation (AF). The mechanism of this increased risk is unknown. Furthermore, both the molecular effects of CRP on atrial myocytes and fibroblasts and whether genetic variants in the CRP gene predispose to AF are also unknown. METHODS: A genetic association study between CRP gene polymorphisms and AF was performed in two independent populations (I: 100 AF patients and 101 controls; II: 348 AF patients and 356 controls), with functional studies to elucidate the mechanism of association. RESULTS: Three polymorphisms (T-861C, A-821G and C-390A/C-390T) were found in the 1-kb promoter of CRP. A triallelic polymorphism (C-390A/C-390T) captured all haplotype information and determined the CRP gene promoter activity and the plasma CRP level, and was in nearly complete linkage disequilibrium with G1059C polymorphism in exon 2. The -390A variant was associated with a higher CRP gene promoter activity, a higher plasma CRP level and a higher risk of AF. Patients with AF also had a higher plasma CRP level than controls. CRP significantly increased the inward L-type calcium current in atrial myocytes with no changes in other ionic currents. CRP did not affect the expressions of type I alpha 1 (COL1A1), type III alpha 1 (COL3A1) and type 1 alpha 2 (COL1A2) procollagens in atrial fibroblasts. CONCLUSION: A CRP gene promoter triallelic polymorphism was associated with CRP gene promoter activity, determined the plasma level of CRP, and predicted the risk of AF. The mechanism of this may be via augmention of calcium influx by CRP in atrial myocytes, but not because of atrial fibrosis.

Differential association of proinflammatory cytokines with left ventricular diastolic dysfunction in subjects with and without continuous ambulatory peritoneal dialysis.

BACKGROUND AND AIMS: The association between inflammation and left ventricular (LV) diastolic dysfunction in continuous ambulatory peritoneal dialysis (CAPD) and non-CAPD patients is not established. The objective of this study was to test the above association and whether inflammation interacts with CAPD to increase LV diastolic dysfunction risks. METHODS AND RESULTS: 120 subjects with normal creatinine levels and 101 CAPD patients were recruited. Echocardiographic parameters were assessed in all patients. The participants were classified as having LV diastolic dysfunction by echocardiographic findings including mitral inflow E/A ratio < 1, deceleration time > 220 cm/s, or decreased peak annular early diastolic velocity in tissue Doppler imaging. Blood was sampled at the baseline for measurement of inflammation markers, including tissue necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Subjects with LV diastolic dysfunction had higher proinflammation cytokines levels in both groups. Inflamed markers correlated significantly with echocardiography parameters for LV diastolic dysfunction in patients receiving CAPD. In a multivariate regression analysis adjusting for all the factors associated with LV diastolic dysfunction, inflammation is still significantly associated with left ventricular diastolic dysfunction (TNF-alpha, OR: 2.6, 95% CI: 2.0-3.35, p < 0.001; IL-6, OR: 1.26, 95% CI: 1.25-1.26, p = 0.01). In addition, the interaction of CAPD and inflammation significantly contributed to the development of LV diastolic dysfunction (CAPD∗ TNF-α: OR: 1.45, 95% CI: 1.13-1.79, P = 0.004). CONCLUSION: We found inflammation plays a vital role for LV diastolic dysfunction especially in CAPD patients. A synergistic effect between CAPD and inflammation, especially TNF-α, would further aggravate LV diastolic dysfunction.

Aging renders the brain vulnerable to amyloid beta-protein neurotoxicity.

The formation of fibrillar deposits of amyloid beta protein (Abeta) in the brain is a pathological hallmark of Alzheimer's disease (AD). A central question is whether Abeta plays a direct role in the neurodegenerative process in AD. The involvement of Abeta in the neurodegenerative process is suggested by the neurotoxicity of the fibrillar form of Abeta in vitro. However, mice transgenic for the Abeta precursor protein that develop amyloid deposits in the brain do not show the degree of neuronal loss or tau phosphorylation found in AD. Here we show that microinjection of plaque-equivalent concentrations of fibrillar, but not soluble, Abeta in the aged rhesus monkey cerebral cortex results in profound neuronal loss, tau phosphorylation and microglial proliferation. Fibrillar Abeta at plaque-equivalent concentrations is not toxic in the young adult rhesus brain. Abeta toxicity in vivo is also highly species-specific; toxicity is greater in aged rhesus monkeys than in aged marmoset monkeys, and is not significant in aged rats. These results suggest that Abeta neurotoxicity in vivo is a pathological response of the aging brain, which is most pronounced in higher order primates. Thus, longevity may contribute to the unique susceptibility of humans to Alzheimer's disease by rendering the brain vulnerable to Abeta neurotoxicity.

Demonstrating the pharmacogenetic effects of angiotensin-converting enzyme inhibitors on long-term prognosis of diastolic heart failure.

The objective of this study was to evaluate the effects of angiotensin-converting enzyme (ACE) inhibitors and pharmacogenetic interaction on the survival of the patients with diastolic heart failure (DHF). A total of 285 subjects with DHF confirmed by echocardiography were recruited in the period between 1995 and 2003. Baseline characteristics (age, sex, prior history, medication, and echocardiographic findings) and genetic polymorphisms (ACE gene insertion/deletion (I/D) polymorphism; T174M, M235T, G-6A, A-20C, G-152A, and G-217A polymorphisms of the angiotensinogen (AGT) gene; and A1166C polymorphisms of the angiotensin II type I receptor (AT1R)) were collected and matched (by propensity score) in those who received and those who did not receive ACE inhibitors. The patients were followed up to 10 years. Kaplan-Meier curves and Cox regression models were used to demonstrate the survival trend. The 85 patients who received ACE inhibitors and the other 85 patients who did not were found to have comparable baseline characteristics and polymorphism distribution. Prescription of ACE inhibitors was associated with a significant decrease in overall mortality (hazard ratio (HR), 0.45; 95% confidence interval (CI), 0.24-0.83; P=0.01), and a lower rate of cardiovascular events at 4000 days (HR, 0.53; 95% CI, 0.32-0.90; P=0.02). In addition, ACE I/D gene D allele was associated with higher overall mortality as compared with the I allele (HR, 2.04; P=0.003). This effect was diminished in those who received ACE inhibitors. The use of ACE inhibitor was associated with a significant decrease in long-term mortality and cardiovascular events in the patients with DHF. Genetic variants in the renin-angiotensin system genes were also associated, but their effects could be modified by the use of ACE inhibitors.

[Comparison the clinical efficacy of 3D versus 2D total laparoscopic thyroidectomy for thyroid cancer by via-breast approach].

Objective:To summarize and analyze the clinical efficacy of 3D and 2D laparoscopic surgery in thyroidectomy for thyroid cancer. Method: Thirty-seven patients with early-differentiated thyroid cancer underwent laparoscopic surgery from August 2016 to November 2018. Their clinical data were retrospectively analyzed. They were divided into 3D laparoscopic group and 2D laparoscopic group based on laparoscopic imaging systems. The perioperative clinical indicators and postoperative complications of the two groups were compared. Result: Compared with the 2D laparoscopic group, the 3D laparoscopic group had shorter operation time and less bleeding, and the incidence of postoperative complications was less, but the differences between the two groups were not statistically significant(P>0.05). Conclusion: Compared with the 2D laparoscopic thyroidectomy, 3D laparoscopic thyroidectomy for thyroid cancer allows higher surgical precision, shorter operation time, lower operation risk and smoother surgical procedure, thus improves surgical efficiency.

Renin-angiotensin system gene polymorphisms and diastolic heart failure.

BACKGROUND: Diastolic heart failure (DHF) refers to an abnormality of diastolic distensibility, filling or relaxation of the left ventricle. The genetic study of DHF is scarce in the literature. The association of renin-angiotensin system (RAS) and DHF are well known. We hypothesized that RAS genes might be the susceptible genes for DHF and conducted a case-control study to prove the hypothesis. MATERIALS AND METHODS: A total of 1452 consecutive patients were analysed and 148 patients with a diagnosis of DHF confirmed by echocardiography were recruited. We had two control populations. The first controls consisted of 286 normal subjects while the second were 148 matched controls selected on a 1-to-1 basis by age, sex, hypertension, diabetes and medication use. The angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism; multilocus polymorphisms of the angiotensinogen gene; and the A1166C polymorphisms of the angiotensin II type I receptor (AT(1)R) gene were genotyped. RESULTS: In a single-locus analysis, the odds ratios (ORs) for DHF were significant with the ACE DD genotype and the AT(1)R 1166 CC plus AC genotype. In addition, the concomitant presence of ACE DD and AT(1)R 1166 CC/AC genotypes synergistically increased the predisposition to DHF. CONCLUSIONS: Genetic variants in the RAS genes may determine an individual's risk to develop DHF. There is also a synergistic gene-gene interaction between the RAS genes in the development of DHF.

UV treatments on the physicochemical properties of tilapia skin and pig skin gelatin.

Tilapia skin gelatin, pig skin gelatin, and their mousse premixes were exposed to UV irradiation for 103, 206, and 309 kJ/cm(2). All samples after 309 kJ/cm(2) exposure exhibited a significant increase in gel strength, gel forming ability as well as viscosity of solutions. It was shown that UV treatment could also improve the pig skin gelatin foam stability and foam formation ability compared to those of tilapia skin gelatin. Nevertheless, the panelists gave the lowest scores to mousse made with 309 kJ/cm(2) UV-irradiated premix mousse pig skin gelatin. Tilapia skin gelatin could be used as a substitute ingredient for premix mousse made from pig skin gelatin.

Structures of an unliganded neurophysin and its vasopressin complex: implications for binding and allosteric mechanisms.

The structures of des 1-6 bovine neurophysin-II in the unliganded state and as its complex with lysine vasopressin were determined crystallographically at resolutions of 2.4 A and 2.3 A, respectively. The structure of the protein component of the vasopressin complex was, with some local differences, similar to that determined earlier of the full-length protein complexed with oxytocin, but relatively large differences, probably intrinsic to the hormones, were observed between the structures of bound oxytocin and bound vasopressin at Gln 4. The structure of the unliganded protein is the first structure of an unliganded neurophysin. Comparison with the liganded state indicated significant binding-induced conformational changes that were the largest in the loop region comprising residues 50-58 and in the 7-10 region. A subtle binding-induced tightening of the subunit interface of the dimer also was shown, consistent with a role for interface changes in neurophysin allosteric mechanism, but one that is probably not predominant. Interface changes are suggested to be communicated from the binding site through the strands of beta-sheet that connect these two regions, in part with mediation by Gly 23. Comparison of unliganded and liganded states additionally reveals that the binding site for the hormone alpha-amino group is largely preformed and accessible in the unliganded state, suggesting that it represents the initial site of hormone protein recognition. The potential molecular basis for its thermodynamic contribution to binding is discussed.

Relationship between plaques, tangles, and loss of cortical cholinergic fibers in Alzheimer disease.

Recent observations in our laboratory have indicated substantial and systematic regional variations in the loss of cortical cholinergic fibers in Alzheimer disease (AD). Previous attempts to study the relationship between cortical cholinergic loss and the density of cortical pathological lesions have resulted in conflicting findings. Furthermore, most reports have correlated density of plaques and tangles with the residual level of cholinergic innervation rather than its loss. The purpose of the present study was to determine the relationship between loss of cholinergic axons and density of tangles and beta-amyloid (Abeta) deposits in various cortical areas of AD brains. Abeta deposits and tangles were observed throughout the cerebral cortex. Quantitative analysis revealed almost no correlation between loss of cholinergic fibers and the density of Abeta deposits. Qualitative observations revealed similar results when cored and neuritic plaques were considered separately. By contrast, cholinergic fiber loss displayed a significant correlation with the density of tangles (r = 0.52-0.79). However, in a few areas, such as the cingulate cortex, tangle density appeared to be unrelated to the loss of cholinergic fibers. These results indicate that cortical cholinergic denervation in AD is related to cytoskeletal pathology. However, the lack of a perfect relationship with cytoskeletal pathology implicates additional factors in the cholinergic pathology of AD.

Selective cell loss in Edinger-Westphal in asymptomatic elders and Alzheimer's patients.

Exaggerated pupillary response to a low concentration of cholinergic antagonists has been suggested as an early marker for Alzheimer's Disease (AD). To examine the anatomic basis of this phenomenon, we determined possible neuropathological changes in the Edinger-Westphal (EW) nucleus, a midbrain neural center with a significant functional role in the control of pupil size. Stereologically determined neuronal numbers within the EW were counted in individuals with pathologically confirmed AD, control cases with no AD-type pathology, and subjects with AD pathology not meeting diagnostic criteria for AD. The EW of AD patients displayed a marked and striking neuronal loss when compared with controls. In contrast, the number of neurons in the somatic portion of the nucleus of the third cranial nerve (NCNIII) remained intact. The EW in brains from clinically normal individuals with evidence of early AD-type pathology also displayed a significant and selective loss of neurons. The magnitude of EW neuronal loss in the latter group was smaller than that observed in AD. These findings suggest that pupillary hypersensitivity in AD may be caused by abnormalities in the EW. Neuronal loss and pathology within the EW in a subpopulation of clinically silent controls with pathologic findings consistent with early-stage AD constitutes a possible explanation for the reported exaggerated pupil response in some normal elderly subjects.

Selective age-related loss of calbindin-D28k from basal forebrain cholinergic neurons in the common marmoset (Callithrix jacchus).

A significant number of the cholinergic neurons in the basal forebrain of the primate, but not the rodent brain contain the calcium binding protein calbindin-D28k (CB). Previous experiments in our laboratory have demonstrated a substantial age-related loss of CB from the human basal forebrain cholinergic neurons (BFCN). The present study investigated the possible age-related loss of CB from the BFCN in a non-human primate species, the common marmoset (Callithrix jacchus). Quantitative analysis of matching sections as well as unbiased stereological determination of neuronal number were used in 16 adult marmosets ranging in age between 2 and 15 years. No significant changes were observed in the number of choline acetyltransferase-positive BFCN when a group of young animals (< or =4 years) was compared with a 6-8-year-old group and a 9-15-year-old group. Similarly, no age-related changes were observed in Nissl-stained magnocellular basal forebrain (putatively cholinergic) neurons. In contrast, the BFCN of the two older groups of animals displayed a significant loss of CB. The age-related loss of CB occurred in all sectors of the BFCN, but was greatest in the anterior sector of this cell group. The CB loss was neurochemically specific since the BFCN in the older groups of animals continued to express other markers such as high and low affinity neurotrophin receptors. The age-related loss of CB from the marmoset BFCN was also regionally selective as CB positive neurons in other structures, such as the cerebral cortex and the striatum displayed no apparent age-related changes. These results indicate that the marmoset BFCN display a significant and selective age-related loss of CB reminiscent of that observed in the human. Therefore, the common marmoset represents an appropriate animal model in which the consequences of BFCN CB loss can be investigated in depth. Loss of CB from the aged BFCN is likely to reduce the capacity of these neurons to buffer intracellular calcium and to leave them vulnerable to insults which can result in increased calcium levels. The vulnerability of the CB-negative BFCN in the aged marmoset to various insults which disturb calcium homeostasis remains to be investigated.

Age-related loss of calbindin from human basal forebrain cholinergic neurons.

Loss of basal forebrain cholinergic neurons (BFCN) occurs in many age-related neurological diseases. Although age is the common risk factor in these disorders, no consistent age-related changes have been reported in the human BFCN. We investigated age-related alterations in choline acetyltransferase (ChAT), low-affinity nerve growth factor receptor (p75LNGFR) and calbindin-D28k (CalBP) immunoreactivity in the human BFCN. No significant age-related changes were observed in ChAT or p75LNGFR immunoreactivity. By contrast, normal aging was accompanied by a selective, substantial and significant loss of CalBP immunoreactivity from the BFCN. Other CalBP-positive neurons were unchanged. Loss of the calcium buffering capacity conferred by CalBP may leave the BFCN vulnerable to damage in neurodegenerative disorders.

Laser-induced multiphoton fluorescence of hemoglobin.

Hemoglobin (Hb) and other samples were irradiated by the 1064 nm nanosecond pulses of an Nd:YAG laser. At room temperature, we observed two red fluorescence bands, which resulted from the absorption of two 1064 nm photons in Hb, and measured the fluorescence emission spectra in the red spectral region for Hb and hematoporphyrin derivative. A red shift of the wavelength and a mirror image in the intensity of fluorescence emissions by two-photon excitation were observed. It is shown that the fluorescence of Hb originates from the heme group. In addition, we also observed fluorescence emission at 392 nm for Hb, which may be from its tryptophan groups.

Effects of infused glucose, sodium and potassium chlorides and polyphosphates on palatability of hot-boned pork.

Longissimus muscle sections were excised from eight pork carcasses 1 h postmortem and sectioned into six .5-kg roasts to determine the effects of glucose, salt and polyphosphates (aqueous solution to 110% of fresh weight) on palatability of hot-boned pork. Treatments were hot-boned control (HB) with no infusion or infusions of 2% KCl and 3% of a 1:1 mixture of sodium hexametaphosphate and sodium pyrophosphate (PP) plus either 8% NaCl; 2% glucose (G) plus 6% NaCl; 6% G plus 2% NaCl; or 8% G. Another muscle section was chilled at 0 degrees C for 24 h on each carcass as a cold-processed control (CP). The roasts were frozen until cooked and evaluated by a sensory panel. The infused groups were more tender, juicy and salty and higher in moisture and ash but lower in protein content than either the CP or HB controls (P less than .05). The fat content of the infused groups was lower than of the HB control but was not different from that of the CP control. Either 2% NaCl plus 6% G or equal amounts (4%) of NaCl and G produced the most tender and juicy product. The substitution of 4% glucose for NaCl not only reduced the NaCl content of the infusion solution, but also improved the palatability of the meat. This substitution allows production of a hot-boned, lower-sodium precooked pork that is tender and juicy.

Effects of breed type and accelerated fat removal on subprimal yields and carcass values.

Nine Brown Swiss and nine English crossbred steers representing the industry standard were slaughtered to determine the effects of cattle type and hot fat removal on subprimal yields and carcass value. After dressing, cod fat, kidney, pelvic, and heart fat (KPHF), and subcutaneous fat thicker than .6 cm was removed from the right side of each carcass (HFT). The left side was not hot-fat trimmed (NFT). Both sides were fabricated into subprimal cuts with no more than .6 cm of subcutaneous fat. Carcass side values were adjusted to a 300-kg chilled carcass weight basis. All comparisons were made for the carcasses using a USDA Select quality grade end point. English crossbred steer carcasses had more (P < .05) subcutaneous fat on the loin and chuck and more (P < .05) total hot fat trim, when KPHF was not included, than Brown Swiss steers (P < .05). Brown Swiss steers had more (P < .05) KPHF. Hot-fat trimmed sides had higher (P < .05) percentage yields from the chuck, brisket, foreshank, rib, plate, round primal cuts, and most of the subprimal cuts than NFT sides, but the primal loin percentage was higher (P < .05) in the NFT sides. The total subprimal cuts yield was approximately 5% higher for the HFT sides than for the NFT sides, and the total fat trim during fabrication was more than 6% less. When the value of the sides was calculated from unadjusted weights, the NFT sides were approximately $26.50 more valuable than the HFT sides.(ABSTRACT TRUNCATED AT 250 WORDS)

Microbiology of hot-fat-trimmed beef.

The effects of removal of fat from hot beef carcasses on the shelf life of beef involved measuring the incidence of aerobic (TPC), lactic (LAC), and coliform (TCC) bacteria and the pathogen Escherichia coli (EC) from alternate sides that were hot-fat trimmed (HFT) or not trimmed (NFT) then subjected to a conventional 24-h chill. The biceps femoris, psoas major, longissimus thoracis et lumborum, and supraspinatus muscles were assayed. Higher (P < .05) TPC and EC counts were found for all muscles at 0 d than at 7 and 14 d of storage. The LAC and TCC counts were higher (P < .05) on all muscles after the 14 d of storage than after 0 or 7 d of storage. The significant differences in microbial counts were less than one log 10/g of tissue and therefore are of questionable importance. The HFT did not increase carcass microbial load compared with NFT. This study showed that HFT and accelerated processing of beef for the production of lean retail cuts did not adversely affect the shelf-life of vacuum-packaged beef.

Restaurant consumer acceptance of beef loin strip steaks tenderized with calcium chloride.

Beef strip loins from either the right or left side of 22 carcasses of Bos indicus-type steers were injected with 200 mM calcium chloride (CaCl2) solution at 5% (wt/wt) to determine its effect on tenderness and other selected quality traits of steaks. Loins from opposite sides of the carcasses were untreated and served as the control. The steaks were evaluated for tenderness, juiciness, flavor intensity, tenderness acceptability, and overall acceptability by 62 restaurant consumers over a 6-wk period. The CaCl2 injection improved (P < .05) tenderness and flavor intensity ratings by the restaurant consumers. Tenderness acceptability and overall acceptability were improved 23 and 17%, respectively, by the CaCl2 injection. Flavor was not compromised by the CaCl2 injection. The CaCl2-treated steaks were rated superior(P < .05) for flavor compared to the control steaks. Restaurant consumers preferred the beef loin strip steaks injected with 200 mM CaCl2 at 5% (wt/wt). The results of this study are interpreted to indicate that, from a restaurant consumer perspective, CaCl2 injection is an acceptable means of making beef a more consistently tender product.