World-Wide FINGERS Network: A global approach to risk reduction and prevention of dementia.

Reducing the risk of dementia can halt the worldwide increase of affected people. The multifactorial and heterogeneous nature of late-onset dementia, including Alzheimer's disease (AD), indicates a potential impact of multidomain lifestyle interventions on risk reduction. The positive results of the landmark multidomain Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) support such an approach. The World-Wide FINGERS (WW-FINGERS), launched in 2017 and including over 25 countries, is the first global network of multidomain lifestyle intervention trials for dementia risk reduction and prevention. WW-FINGERS aims to adapt, test, and optimize the FINGER model to reduce risk across the spectrum of cognitive decline-from at-risk asymptomatic states to early symptomatic stages-in different geographical, cultural, and economic settings. WW-FINGERS aims to harmonize and adapt multidomain interventions across various countries and settings, to facilitate data sharing and analysis across studies, and to promote international joint initiatives to identify globally implementable and effective preventive strategies.

Nomogram for predicting postoperative pancreatic fistula.

BACKGROUND: Previous studies analyzed risk factors for postoperative pancreatic fistula (POPF) and developed risk prediction tool using scoring system. However, no study has built a nomogram based on individual risk factors. This study aimed to evaluate individual risks of POPF and propose a nomogram for predicting POPF. METHODS: From 2007 to 2016, medical records of 1771 patients undergoing pancreaticoduodenctomy were reviewed retrospectively. Variables with p < 0.05 in multivariate logistic regression analysis were included in the nomogram. Internal performance validation was executed using a repeated cross validation method. RESULTS: Of 1771 patients, 222 (12.5%) experienced POPF. In multivariable analysis, sex (p = 0.004), body mass index (BMI) (p < 0.001), ASA score (p = 0.039), preoperative albumin (p = 0.035), pancreatic duct diameter (p = 0.002), and location of tumor (p < 0.001) were identified as independent predictors for POPF. Based on these six variables, a POPF nomogram was developed. The area under the curve (AUC) estimated from the receiver operating characteristic (ROC) graph was 0.709 in the train set and 0.652 in the test set. CONCLUSIONS: A POPF nomogram was developed. This nomogram may be useful for selecting patients who need more intensified therapy and establishing customized treatment strategy.

Neoadjuvant therapy versus upfront surgery for borderline-resectable pancreatic cancer.

BACKGROUND: Neoadjuvant therapy is recommended for patients with borderline-resectable pancreatic cancer (BRPC). In this study, we compare survival outcomes of neoadjuvant therapy with upfront surgery. METHODS: From January 2011 to June 2016, 1415 patients underwent treatments for pancreatic cancer in Samsung Medical Center. Among them, 112 (7.9%) patients were categorized as BRPC by the NCCN 2016 guideline. They were classified by type of initial treatments into neoadjuvant group (NA, N.=26) and upfront surgery group (US, N.=86). RESULTS: The median survival duration of all patients was 18.3 months. Patients in the NA group had more T4 disease than those in the US group (38.5% in NA versus 15.1% in the US group; P=0.010). Arterial involvement was more frequent in the NA group (42.3% versus 15.1%; P=0.003). In the NA group, ten (38.5%) patients underwent surgery, and seven of them had complete R0 resection. In the US group, 83 (96.5%) patients received radical surgery, and 42 (48.8%) had R0 resection. In survival analysis according to intent to treat, the overall two-year survival rate was 51.1% in the US group and 36.7% in the NA group (P=0.001). However, among patients who underwent surgery (N.=96), the two-year overall survival rate was not significantly different between the two groups (P=0.089). According to involved vessels, the survival rate was not different between patients with arterial or both arterial and venous involvement and in patients with only venous involvement (P=0.649). CONCLUSIONS: It is necessary to demonstrate the efficacy of neoadjuvant therapy and to standardize the regimens through large-scale, multicenter, randomized controlled studies.

Oleic acid in the absence of a PPARγ agonist increases adipogenic gene expression in bovine muscle satellite cells1.

We hypothesized that oleic acid (OA) in the absence of a thiazolidinedione (i.e., a synthetic peroxisome proliferator-activated receptorγ [PPARγ] agonist) would increase adipogenic gene expression in bovine muscle satellite cells (BSC). The BSC were cultured in differentiation medium containing 10 µM ciglitazone (CI), 100 µM OA, or 100 µM OA plus 10 µM CI (CI-OA). Control (CON) BSC were cultured only in differentiation media (containing 2% horse serum). The presence of myogenin, desmin, and paired box 7 proteins was confirmed in the BSC by immunofluorescence staining, demonstrating that we had isolated myogenic cells. The OA BSC had lesser paired box 3 (Pax3) and myogenic differentiation 1 expression but greater Pax7 and mygogenin (MYOG) expression (P < 0.05), than the CON BSC. The CI BSC had greater Pax3, Pax7, and MYOG expression than CON BSC (P < 0.05), suggesting that CI would promote BSC myogenesis under pro-myogenic conditions (i.e., when cultured with horse serum). However, both the OA and CI treatments upregulated the expression of PPARγ, CCAAT/enhancer-binding protein alpha (C/EBPα) and C/EBPß, sterol regulatory element-binding protein 1, lipoprotein lipase, and glycerol-3-phosphate acyltransferase 3 gene expression, as well as media adiponectin concentration (P < 0.05). The CI, OA, and CI-OA treatments also increased triacylglycerol and lipid droplet accumulation, in spite of upregulation (relative to CON BSC) of adenosine monophosphate-activated protein kinase alpha-1, perilipin 2 (PLIN2), and PLIN3 in BSC and downregulation of G protein-coupled protein receptor 43, acyl-CoA synthetase long chain family member 3, and stearoyl-CoA desaturase (P < 0.05). These results indicate that OA in the absence of a synthetic PPARγ agonist can effectively increase adipogenic gene expression in BSC.

Ground Beef High in Total Fat and Saturated Fatty Acids Decreases X Receptor Signaling Targets in Peripheral Blood Mononuclear Cells of Men and Women.

We hypothesized that consumption of saturated fatty acids in the form of high-fat ground beef for 5 weeks would depress liver X receptor signaling targets in peripheral blood mononuclear cells (PBMC) and that changes in gene expression would be associated with the corresponding changes in lipoprotein cholesterol (C) concentrations. Older men (n = 5, age 68.0 ± 4.6 years) and postmenopausal women (n = 7, age 60.9 ± 3.1 years) were assigned randomly to consume ground-beef containing 18% total fat (18F) or 25% total fat (25F), five patties per week for 5 weeks with an intervening 4-week washout period. The 25F and 18F ground-beef increased (p < 0.05) the intake of saturated fat, monounsaturated fat, palmitic acid, and stearic acid, but the 25F ground-beef increased only the intake of oleic acid (p < 0.05). The ground-beefs 18F and 25F increased the plasma concentration of palmitic acid (p < 0.05) and decreased the plasma concentrations of arachidonic, eicosapentaenoic, and docosahexaenic acids (p < 0.05). The interventions of 18F and 25F ground-beef decreased very low-density lipoprotein C concentrations and increased particle diameters and low-density lipoprotein (LDL)-I-C and LDL-II-C concentrations (p < 0.05). The ground-beef 25F decreased PBMC mRNA levels for the adenosine triphosphate (ATP) binding cassette A, ATP binding cassette G1, sterol regulatory element binding protein-1, and LDL receptor (LDLR) (p < 0.05). The ground-beef 18F increased mRNA levels for stearoyl-CoA desaturase-1 (p < 0.05). We conclude that the increased LDL particle size and LDL-I-C and LDL-II-C concentrations following the 25F ground-beef intervention may have been caused by decreased hepatic LDLR gene expression.

Adipogenic/lipogenic gene expression and fatty acid composition in chuck, loin, and round muscles in response to grain feeding of Yanbian Yellow cattle.

We hypothesized that gene expression and fatty acid composition would differ among different muscle depots and over time on a grain-based finishing diet. Additionally, we hypothesized that the concentration of SFA would decrease and the concentration of MUFA would increase proportionately with increases in percent intramuscular lipid (%IML). Ten Yanbian Yellow cattle steers (approximately 8 mo of age) were fed a corn-based diet in which the proportion of corn in the ration was increased at 4-mo intervals. Muscle samples were taken by biopsy from the chuck (trapezius), loin (longissimus dorsi), and round (biceps femoris) muscles at 12, 16, 20, 24, and 28 mo of age. The %IML increased from 12 to 28 mo of age, especially between 24 and 28 mo of age, with loin > round > chuck (age × muscle interaction P < 0.001). The percentage (g/100 g total fatty acids) of oleic acid (18:1n-9), linoleic acid (18:2n-6), and α-linolenic acid (18:3n-3), and the MUFA:SFA ratio increased with age, whereas palmitic (16:0) and stearic acid (18:0) decreased with age in all muscles (age effect P < 0.001). The expression of sterol regulatory element binding protein (SREBP1), adipose tissue fatty acid- binding protein (FABP4), stearoyl-CoA desaturase (SCD), acetyl-CoA carboxylase (ACC1), and lipoprotein lipase (LPL) increased, whereas the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and fatty acid synthase (FASN) decreased with age. Expression of PPARγ, FABP4, SREBP1, SCD, FASN, ACC1, and LPL was greater in the loin than in the chuck or round (age × muscle interaction P < 0.001), although the MUFA:SFA ratio was greater in the chuck than in the loin or round (muscle effect P < 0.001). In conclusion, adipogenic gene expression was greater in the loin than in the chuck or round muscles, consistent with the greater %IML of the loin. However, the greater SCD gene expression in the loin did not result in a greater amount of MUFA in the loin, relative to the chuck and round.

Effects on agitation with rivastigmine patch monotherapy and combination therapy with memantine in mild to moderate Alzheimer's disease: a multicenter 24-week prospective randomized open-label study (the Korean EXelon Patch and combination with mEmantine Comparative Trial study).

AIM: Memantine is known to be effective in the treatment of the behavioral symptoms of dementia, especially agitation in moderate to severe Alzheimer's disease (AD). However, memantine and rivastigmine patch combination therapy has not been well studied in determining treatment effectiveness with mild to moderate AD patients. METHODS: This was a multicenter, 24-week, prospective, randomized, open-label study design. A total 147 AD patients with Mini-Mental State Examination scores from 10 to 20 were randomly assigned to rivastigmine patch monotherapy and combination therapy with memantine groups. Agitation symptoms, using the Korean Version of the Cohen Mansfield Agitation Inventory were evaluated at baseline and at study end. Suppression and emergence of agitation symptoms were also evaluated. We carried out factor analyses to evaluate the interrelationship of agitation symptoms and to investigate treatment response in these symptoms. RESULTS: Factor analyses showed two symptom clusters: factor A - aggressive agitated behaviors - versus factor B - non-aggressive agitated behaviors. The rivastigmine patch monotherapy group showed significantly decreased factor B scores and had a tendency of decreased Korean Version of the Cohen Mansfield Agitation Inventory total scores and factor A scores. Conversely, the combination therapy group showed significantly increased Korean Version of the Cohen Mansfield Agitation Inventory total scores and factor B scores. Neither monotherapy nor combination therapy reduced the emergence of new agitation symptoms. CONCLUSIONS: In this trial of mild to moderate AD patients, the rivastigmine patch monotherapy group experienced a reduction of non-aggressive agitated behaviors. However, combination therapy with memantine did not show any benefit on the agitation associated with mild to moderate AD. Geriatr Gerontol Int 2017; 17: 494-499.

Localization and surgical treatment of the pancreatic insulinomas.

OBJECTIVES: Insulinomas are rare tumours that originate from the islet cells of the pancreas. The aims of this study were to gain an understanding of the clinical features of insulinomas and to establish the diagnostic and therapeutic strategies. METHODS: A review was carried out in 20 patients with insulinoma surgically treated in our institution over the last 10 years. Presenting symptoms, biochemical studies, preoperative and intraoperative localization studies, operative management and complications were analysed. RESULTS: The male-to-female ratio was 8:12, with a mean age of 46.4 years. Each patient suffered from significant neuroglycopenic symptoms, usually manifested by dizziness, sweating, headache and confusion. The preoperative median serum levels of glucose, insulin and C-peptide at the termination of the fast were 37.5 mg/dL, 23.5 microU/mL, 5.6 ng/mL, respectively. Preoperative tumour localization was achieved by means of ultrasonography (US), computed tomography, selective angiography or intra-arterial calcium injection with hepatic venous sampling, and sensitivities of these examinations were 81.8, 73.7, 94.1 and 100%, respectively. Intraoperative localization was carried out by a combination of manual palpation and intraoperative US with retrospective sensitivities of 80 and 100%, respectively. Enucleation was carried out in 16 patients and distal pancreatectomy in 4. The mortality and morbidity rates were 0 and 10%, respectively. One patient developed late diabetes mellitus type 1 after distal pancreatectomy. CONCLUSIONS: We conclude that the diagnosis of insulinoma can be made on the basis of the results of a supervised fast, careful palpation with intraoperative US is essential for intraoperative detection of insulinomas and surgical resection is the best choice for treatment of benign insulinomas.

Long-term outcome of portomesenteric vein invasion and prognostic factors in pancreas head adenocarcinoma.

BACKGROUND: The purpose of this study was to clarify the post-operative prognosis of pancreatic head cancer with pathologic portal vein (PV) or superior mesenteric vein (SMV) invasion. METHODS: From May 1995 to December 2009, preoperative, intra-operative and post-operative data from 276 patients who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma were reviewed retrospectively. The long-term prognosis was compared between patients with a pathologic PV-SMV invasion and those without invasion. RESULTS: Fourty-six patients (16.7%) underwent PV-SMV resection during pancreaticoduodenectomy. Pathologic PV-SMV invasion was observed in 30 (65.2%). Post-operative severe morbidity (grade 3 or 4) was similar for patients with and without PV-SMV resection (8.7% with versus 7.0% without P = 0.754). The mortality rate was 2.2% with PV-SMV resection and 0.9% without PV-SMV resection (P = 0.423). Survival of PV-SMV resection and no resection group had no significant difference (median survival, 16 versus 12 months; P = 0.086). No significant difference in overall survival was seen between patients with and without pathologic PV-SMV invasion (median survival, 13 versus 16 months; P = 0.663). Tumour differentiation, R status, tumour size and type of operation were revealed as independent prognostic factors. CONCLUSIONS: 34.8% of patients who underwent PV-SMV resection had no pathologic invasion. And PV-SMV resection did not increase the rate of severe complications and mortality. Furthermore, the prognosis for patients with pathologic PV-SMV invasion may be nearly the same as patients with no invasion. So, PV-SMV resection with reconstruction should be considered in pancreatic head cancer patients with suspected PV-SMV invasion.

Effects of dietary linseed oil and propionate precursors on ruminal microbial community, composition, and diversity in Yanbian yellow cattle.

The rumen microbial ecosystem is a complex system where rumen fermentation processes involve interactions among microorganisms. There are important relationships between diet and the ruminal bacterial composition. Thus, we investigated the ruminal fermentation characteristics and compared ruminal bacterial communities using tag amplicon pyrosequencing analysis in Yanbian yellow steers, which were fed linseed oil (LO) and propionate precursors. We used eight ruminally cannulated Yanbian yellow steers (510 ± 5.8 kg) in a replicated 4 × 4 Latin square design with four dietary treatments. Steers were fed a basal diet that comprised 80% concentrate and 20% rice straw (DM basis, CON). The CON diet was supplemented with LO at 4%. The LO diet was also supplemented with 2% dl-malate or 2% fumarate as ruminal precursors of propionate. Dietary supplementation with LO and propionate precursors increased ruminal pH, total volatile fatty acid concentrations, and the molar proportion of propionate. The most abundant bacterial operational taxonomic units in the rumen were related to dietary treatments. Bacteroidetes dominated the ruminal bacterial community and the genus Prevotella was highly represented when steers were fed LO plus propionate precursors. However, with the CON and LO diet plus malate or fumarate, Firmicutes was the most abundant phylum and the genus Ruminococcus was predominant. In summary, supplementing the diets of ruminants with a moderate level of LO plus propionate precursors modified the ruminal fermentation pattern. The most positive responses to LO and propionate precursors supplementation were in the phyla Bacteriodetes and Firmicutes, and in the genus Ruminococcus and Prevotella. Thus, diets containing LO plus malate or fumarate have significant effects on the composition of the rumen microbial community.

Conjugated fatty acids and methane production by rumen microbes when incubated with linseed oil alone or mixed with fish oil and/or malate.

We hypothesized that manipulating metabolism with fish oil and malate as a hydrogen acceptor would affect the biohydrogenation process of α-linolenic acid by rumen microbes. This study was to examine the effect of fish oil and/or malate on the production of conjugated fatty acids and methane (CH4 ) by rumen microbes when incubated with linseed oil. Linseed oil (LO), LO with fish oil (LO-FO), LO with malate (LO-MA), or LO with fish oil and malate (LO-FO-MA) was added to diluted rumen fluid, respectively. The LO-MA and LO-FO-MA increased pH and propionate concentration compared to the other treatments. LO-MA and LO-FO-MA reduced CH4 production compared to LO. LO-MA and LO-FO-MA increased the contents of c9,t11-conjugated linoleic acid (CLA) and c9,t11,c15-conjugated linolenic acid (CLnA) compared to LO. The content of malate was rapidly reduced while that of lactate was reduced in LO-MA and LO-FO-MA from 3 h incubation time. The fold change of the quantity of methanogen related to total bacteria was decreased at both 3 h and 6 h incubation times in all treatments compared to the control. Overall data indicate that supplementation of combined malate and/or fish oil when incubated with linseed oil, could depress methane generation and increase production of propionate, CLA and CLnA under the conditions of the current in vitro study.

Caregiver-Administered Neuropsychiatric Inventory (CGA-NPI).

The Neuropsychiatric Inventory (NPI) is used to assess neuropsychiatric symptoms in dementia patients. To reduce clinicians' time taken to administer the NPI, the authors studied a caregiver-administered NPI (CGA-NPI), in which caregivers completed the written form of the NPI worksheet. After a brief presupervision session, the caregivers of 61 dementia patients completed the CGA-NPI by reading through the worksheet. This was followed by a postsupervision session to check if the caregivers had completed the form appropriately. The correlation between the prevalence rates of each neuropsychiatric symptom obtained by the CGA-NPI and those obtained by the NPI was fair to good (kappa = 0.57-0.90) in all domains. All frequency, severity, and caregivers' distress scores of the CGA-NPI correlated significantly with those of the NPI (r> 0.6, P<.001). Total CGA-NPI scores also correlated highly with total NPI scores (r= 0.86, P<.001). These results suggest that the CGA-NPI can substitute for the NPI, saving administration time.

Co-culture of bovine muscle satellite cells with preadipocytes increases PPARγ and C/EBPß gene expression in differentiated myoblasts and increases GPR43 gene expression in adipocytes.

We hypothesized that preadipocyte differentiation would be depressed by differentiating myoblasts, whereas preadipocytes would promote adipogenic gene expression in myoblasts in a co-culture system. We also determined the effects of arginine, a biological precursor of nitric oxide, and/or trans-10, cis-12 conjugated linoleic acid (CLA) on adipogenic gene expression during differentiation of bovine preadipocytes and myoblasts. Bovine semimembranosus satellite cells (BSC) and subcutaneous preadipocytes were isolated from crossbred steers and cultured with 10% fetal bovine serum (FBS)/Dulbecco's modified Eagle medium (DMEM) and 1% antibiotics during the 3-day proliferation period. After proliferation, BSC and preadipocytes were treated for 3 days with 3% horse serum/DMEM and 5% FBS/DMEM with antibiotics, respectively. Media also contained 100 µM oleic acid, 10 µg/ml insulin, 1 µg/ml pioglitazone and 1 µg/ml dexamethasone. Subsequently, the differentiating myoblasts and adipocytes were cultured in their respective media with 5 mM arginine and/or 40 µM trans-10, cis-12 CLA for 4 days. Finally, myoblasts and adipocytes were single- or co-cultured for 2 h singly or in combination. Arginine stimulated SCD gene expression, whereas CLA depressed SCD gene expression in adipocytes and myoblasts (P=.002). Co-culture of adipocytes and myoblasts elicited an increase in C/EBPß and PPARγ gene expression in differentiated myoblasts (P≤.01) and an increase in GPR43 gene expression in adipocytes (P=.01). Expression of AMPKα and CPT1ß was unaffected by co-culture, although SCD gene expression tended (P=.12) to be depressed by co-culture. These experiments demonstrated that co-culture of adipocytes with myoblasts increased adipogenic gene expression in the myoblastic cells.