The Naming Assessment in Multicultural Europe (NAME): Development and Validation in a Multicultural Memory Clinic.

OBJECTIVE: Traditional naming tests are unsuitable to assess naming impairment in diverse populations, given the influence of culture, language, and education on naming performance. Our goal was therefore to develop and validate a new test to assess naming impairment in diverse populations: the Naming Assessment in Multicultural Europe (NAME). METHOD: We carried out a multistage pilot study. First, we generated a list of 149 potentially suitable items - e.g. from published cross-linguistic word lists and other naming tests - and selected those with a homogeneous age of acquisition and word frequency across languages. We selected three to four colored photographs for each of the 73 remaining items; 194 controls selected the most suitable photographs. Thirteen items were removed after a pilot study in 15 diverse healthy controls. The final 60-item test was validated in 39 controls and 137 diverse memory clinic patients with subjective cognitive impairment, neurological/neurodegenerative disease or psychiatric disorders in the Netherlands and Turkey (mean age: 67, SD: 11). Patients were from 15 different countries; the majority completed primary education or less (53%). RESULTS: The NAME showed excellent reliability (Spearman-Brown coefficient: 0.95; Kuder-Richardson coefficient: 0.94) and robust correlations with other language tests (ρ = .35-.73). Patients with AD/mixed dementia obtained lower scores on most (48/60) NAME items, with an area under the curve of 0.88. NAME scores were correlated with age and education, but not with acculturation or sex. CONCLUSIONS: The NAME is a promising tool to assess naming impairment in culturally, educationally, and linguistically diverse individuals.

A Snapshot on the Current Status of Alzheimer's Disease, Treatment Perspectives, in-Vitro and in-Vivo Research Studies and Future Opportunities.

Alzheimer's Disease (AD) is one of the most challenging diseases faced by humankind. AD is still not classified as curable because of the complex structure of pathologies underlying it. As the mean life expectancy of the world population constantly increases, the prevalence of AD and treatment costs for AD also grow rapidly. Current state of the art for AD treatment mainly consists of palliative therapy aimed at providing symptomatic relief and improving the standard of living in patients with AD. However, different research groups are working on more effective and safe drug delivery options aimed at both symptomatic relief and treatment of the underlying mechanisms. In this review, the current prevalence of AD, health costs, pathologies, and available treatment options including the ones in the market and/or under trial have been reviewed. Data in the existing literature have been presented, and future opportunities have been discussed. It is our belief that these nanotechnological products provide the required efficacy and safety profiles to enable these formulations go through phase studies and enter the market after regulatory authority approval, as with cancer. Last, but not the least the metabolomic studies will be providing useful informative data on the early diagnosis of AD, thus may be clinical implications might be delayed with the administration of therapeutic agents at the initial state of the disease.

Artificial intelligence and amniotic fluid multiomics: prediction of perinatal outcome in asymptomatic women with short cervix.

OBJECTIVE: To evaluate the application of artificial intelligence (AI), i.e. deep learning and other machine-learning techniques, to amniotic fluid (AF) metabolomics and proteomics, alone and in combination with sonographic, clinical and demographic factors, in the prediction of perinatal outcome in asymptomatic pregnant women with short cervical length (CL). METHODS: AF samples, which had been obtained in the second trimester from asymptomatic women with short CL (< 15 mm) identified on transvaginal ultrasound, were analyzed. CL, funneling and the presence of AF 'sludge' were assessed in all cases close to the time of amniocentesis. A combination of liquid chromatography coupled with mass spectrometry and proton nuclear magnetic resonance spectroscopy-based metabolomics, as well as targeted proteomics analysis, including chemokines, cytokines and growth factors, was performed on the AF samples. To determine the robustness of the markers, we used six different machine-learning techniques, including deep learning, to predict preterm delivery < 34 weeks, latency period prior to delivery < 28 days after amniocentesis and requirement for admission to a neonatal intensive care unit (NICU). Omics biomarkers were evaluated alone and in combination with standard sonographic, clinical and demographic factors to predict outcome. Predictive accuracy was assessed using the area under the receiver-operating characteristics curve (AUC) with 95% CI, sensitivity and specificity. RESULTS: Of the 32 patients included in the study, complete omics, demographic and clinical data and outcome information were available for 26. Of these, 11 (42.3%) patients delivered ≥ 34 weeks, while 15 (57.7%) delivered < 34 weeks. There was no statistically significant difference in CL between these two groups (mean ± SD, 11.2 ± 4.4 mm vs 8.9 ± 5.3 mm, P = 0.31). Using combined omics, demographic and clinical data, deep learning displayed good to excellent performance, with an AUC (95% CI) of 0.890 (0.810-0.970) for delivery < 34 weeks' gestation, 0.890 (0.790-0.990) for delivery < 28 days post-amniocentesis and 0.792 (0.689-0.894) for NICU admission. These values were higher overall than for the other five machine-learning methods, although each individual machine-learning technique yielded statistically significant prediction of the different perinatal outcomes. CONCLUSIONS: This is the first study to report use of AI with AF proteomics and metabolomics and ultrasound assessment in pregnancy. Machine learning, particularly deep learning, achieved good to excellent prediction of perinatal outcome in asymptomatic pregnant women with short CL in the second trimester. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Metabolomic identification of diagnostic serum-based biomarkers for advanced stage melanoma.

INTRODUCTION: Melanoma is a highly aggressive malignancy and is currently one of the fastest growing cancers worldwide. While early stage (I and II) disease is highly curable with excellent prognosis, mortality rates rise dramatically after distant spread. We sought to identify differences in the metabolome of melanoma patients to further elucidate the pathophysiology of melanoma and identify potential biomarkers to aid in earlier detection of recurrence. METHODS: Using 1H NMR and DI-LC-MS/MS, we profiled serum samples from 26 patients with stage III (nodal metastasis) or stage IV (distant metastasis) melanoma and compared their biochemical profiles with 46 age- and gender-matched controls. RESULTS: We accurately quantified 181 metabolites in serum using a combination of 1H NMR and DI-LC-MS/MS. We observed significant separation between cases and controls in the PLS-DA scores plot (permutation test p-value = 0.002). Using the concentrations of PC-aa-C40:3, DL-carnitine, octanoyl-L-carnitine, ethanol, and methylmalonyl-L-carnitine we developed a diagnostic algorithm with an AUC (95% CI) = 0.822 (0.665-0.979) with sensitivity and specificity of 100 and 56%, respectively. Furthermore, we identified arginine, proline, tryptophan, glutamine, glutamate, glutathione and ornithine metabolism to be significantly perturbed due to disease (p < 0.05). CONCLUSION: Targeted metabolomic analysis demonstrated significant differences in metabolic profiles of advanced stage (III and IV) melanoma patients as compared to controls. These differences may represent a potential avenue for the development of multi-marker serum-based assays for earlier detection of recurrences, allow for newer, more effective targeted therapy when tumor burden is less, and further elucidate the pathophysiologic changes that occur in melanoma.

Preoperative prediction of poor prognostic parameters and adjuvant treatment in women with pure endometrioid type endometrial cancer: what is the significance of tumor markers?

UNLABELLED: Summary PURPOSE OF THE STUDY: The study was conducted to determine whether preoperative serum levels of cancer antigen (CA) 125, CA15- 3, CA19-9, carcinoembryonic antigen (CEA), and alpha-fetoprotein (AFP) are associated clinicopathologically with poor prognostic parameters and adjuvant treatment requirements in women with pure endometrioid endometrial cancer (EEC). MATERIALS AND METHODS: The authors performed a retrospective review of EEC cases that were treated between January 2008 and January 2011. The association between preoperative tumor markers and prognostic parameters, recurrence risk, and adjuvant treatment requirements were investigated. Following univariate analyses, receiver-operating characteristic (ROC) curves were constructed for each marker to assess their capacity to predict prognostic parameters and need for adjuvant treatment. RESULTS: A total of 166 EEC cases were identified. Mean CA125, CA15-3, and CA19-9 levels were higher in cases that required adjuvant treatment (p < 0.05). CA125 had significant power for prediction of extrauterine disease, tumor size > two cm, lymphovascular space invasion (LVSI), deep myometrial invasion, cervical involvement, adnexal involvement, positive cytology, lymph node metastasis, and adjuvant treatment requirement. CA15-3 was a significant marker for adjuvant treatment prediction. CA19-9 could predict deep myometrial invasion, cervical involvement, and adjuvant treatment requirement. However, CEA and AFP did not have adequate capacity to predict any of the poor prognostic parameters and adjuvant treatment requirements. CONCLUSIONs: CA125 is currently one of the most important preoperative markers for identifying EEC cases that exhibit postoperatively poor prognostic pathologic findings and a consequent need for adjuvant treatment. CA15-3 and CA19- 9 were also significant markers with limited capacity in detecting prognostic parameters.

ß-blocker withdrawal among patients presenting for surgery from home.

OBJECTIVE: This study sought to measure the prevalence of perioperative ß-blocker noncompliance by patients who were prescribed long-term ß-blocker therapy and presented for surgery from home. The effect of patient noncompliance on the presenting heart rate on the day of surgery also was examined. DESIGN: Prospective observational study with outcome data obtained from reviews of medical records. SETTING: The preoperative clinic and operating rooms of a Veterans Administration hospital. PARTICIPANTS: Patients on long-term ß-blocker therapy who presented from home for surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic and comorbidity data and data on self-reported compliance to ß-blocker therapy, vital signs on the initial day of surgery, and recent ambulatory vital signs were collected. Ten of 50 subjects (20%; 95% confidence interval, 9-31) reported not taking their ß-blocker on the day of surgery. These self-reported nonadherers exhibited a higher presenting heart rate on the day of surgery than adherent subjects (median, 78 v 65 beats/min; p = 0.02 by Wilcoxon rank-sum test). The difference-in-difference analysis in heart rate between baseline primary care and the day of surgery also was statistically significant between compliant and noncompliant subjects (-7 v + 12.5 beats/min; p < 0.00001). CONCLUSIONS: Patient self-report and physiologic data documented a failure to take ß-blockers and possible ß-blocker withdrawal in 20% of patients who presented for surgery from home. If these findings are confirmed in larger studies, improved patient understanding of and compliance with medication instructions during preoperative visits should be a focus of future quality improvement initiatives.

Spinal tanycytic ependymoma with diffusion restriction on MRI.

Tanycytic ependymoma is a rare spindle-cell variant of ependymoma derived from tanycytes. Primitive neuroectodermal tumors usually have diffusion restriction, whereas ependymomas do not. Here, we present a case of tanycytic ependymoma with diffusion restriction. As far we are aware, this is the first case of tanycytic ependymoma in the English literature with diffusion restriction.

Antimicrobial peptide hCAP-18/LL-37 protein and mRNA expressions in different periodontal diseases.

OBJECTIVE: To investigate the levels of antimicrobial peptide hCAP-18/LL-37 protein and mRNA expression in gingival tissues with different periodontal disease. MATERIALS AND METHODS: Ten patients with generalized aggressive periodontitis, 10 patients with chronic periodontitis, and 10 healthy controls were included in this study. Periodontal parameters including probing depth, clinical attachment level, plaque index, and papilla bleeding index were assessed in study subjects. hCAP-18/LL-37 mRNA analysis by RT-PCR and immunohistochemistry were performed in 19 samples provided enough RNA in terms of concentration and integrity. RESULTS: This study demonstrated that hCAP-18/LL-37 was a product of neutrophils. Tissue samples of chronic periodontitis patients had significantly higher immunostaining of hCAP-18/LL-37 on neutrophils infiltrating in both epithelium and connective tissue compared with controls. hCAP-18/LL-37 mRNA expression levels in tissue samples of chronic periodontitis patients seemed to be upregulated compared with controls. While two generalized aggressive periodontitis patients showed downregulated hCAP-18/LL-37 mRNA expression levels, one generalized aggressive periodontitis patient showed slightly increased hCAP-18/LL-37 mRNA level compared with controls. CONCLUSIONS: hCAP-18/LL-37 has an important role in innate response during periodontal inflammation. Local deficiency in hCAP-18/LL-37 might be a confounding effect in the pathogenesis of generalized aggressive periodontitis.

Expression and regulation of the NALP3 inflammasome complex in periodontal diseases.

Periodontitis is an infectious process characterized by inflammation affecting the supporting structures of the teeth. Porphyromonas gingivalis is a major oral bacterial species implicated in the pathogenesis of periodontitis. Processing of interleukin (IL)-1 family cytokines is regulated by an intracellular innate immune response system, known as the NALP3 [nacht domain-, leucine-rich repeat-, and pyrin domain (PYD)-containing protein 3] inflammasome complex. The aim of the present study was to investigate by quantitative real-time polymerase chain reaction (PCR) the mRNA expression of NALP3, its effector molecule apoptosis associated speck-like protein (ASC), its putative antagonist NLRP2 (NLR family, PYD-containing protein 2), IL-1beta and IL-18 (i) in gingival tissues from patients with gingivitis (n = 10), chronic periodontitis (n = 18), generalized aggressive periodontitis (n = 20), as well as in healthy subjects (n = 20), (ii) in vitro in a human monocytic cell line (Mono-Mac-6), in response to P. gingivalis challenge for 6 h. The clinical data indicate that NALP3 and NLRP2, but not ASC, are expressed at significantly higher levels in the three forms of inflammatory periodontal disease compared to health. Furthermore, a positive correlation was revealed between NALP3 and IL-1beta or IL-18 expression levels in these tissues. The in vitro data demonstrate that P. gingivalis deregulates the NALP3 inflammasome complex in Mono-Mac-6 cells by enhancing NALP3 and down-regulating NLRP2 and ASC expression. In conclusion, this study reveals a role for the NALP3 inflammasome complex in inflammatory periodontal disease, and provides a mechanistic insight to the host immune responses involved in the pathogenesis of the disease by demonstrating the modulation of this cytokine-signalling pathway by bacterial challenge.

The effect of adjunctive chlorhexidine mouthrinse on clinical parameters and gingival crevicular fluid cytokine levels in untreated plaque-associated gingivitis.

OBJECTIVE AND DESIGN: To examine the effectiveness of chlorhexidine mouthrinse (CHX) in addition to daily plaque control on gingival inflammation. METHODS: Fifty gingivitis patients were randomized to CHX or placebo groups. In addition to proper plaque control, CHX group rinsed with CHX, while placebo group rinsed with placebo mouthrinse for 4 weeks. Gingival crevicular fluid (GCF) samples were collected and clinical parameters including plaque index (PI), papillary bleeding index (PBI), calculus index and probing depth (PD) were recorded at baseline and repeated at 4 week. GCF IL-1alpha, IL-1beta, IL-1Ra, and IL-8 levels were determined by ELISA. RESULTS: Whole mouth clinical parameters were significantly improved in both groups at 4 weeks. CHX group showed greater reduction in the mean PI scores than placebo at 4 weeks (p < 0.05). GCF IL-8 levels of anterior sites significantly reduced in CHX and placebo group at 4 weeks (p < 0.05). GCF IL-1alpha, IL-1beta, IL-1Ra levels remained unchanged at 4 weeks in both groups. GCF cytokine levels of CHX group were similar to those of placebo at 4 weeks. CONCLUSIONS: Within the limitations of this study, CHX mouthrinse as adjuncts to daily plaque control could be useful in management of plaque-associated gingivitis, although ineffective on GCF cytokine levels.

Intracranial sewing needle.

A 45-year-old patient was found to have an intracranial sewing needle, located in the left frontal lobe. The needle was detected incidentally after minor head trauma. The clinical and radiological findings suggested that it might have entered the brain through the anterior fontanelle.

The in-vitro and in-vivo characterization of PLGA:L-PLA microspheres containing dexamethasone sodium phosphate.

Dexamethasone sodium phosphate (DSP) is a widely used corticosteroid in the treatment of brain oedema associated with brain tumours. DSP has many side effects that limit its usage at an effective concentration. The objective of this study was to minimize these side effects by encapsulating DSP using biodegradable synthetic polymers, to extend the release time from microspheres and to evaluate the effectiveness in the treatment of brain oedema. Microspheres containing 5% DSP were formulated by the solvent evaporation method by using a 1:1 mixture of two synthetic polymers, poly(lactic-co-glycolic acid) and L-polylactic acid (PLGA and L-PLA). The surface morphologies and particle size distribution of the microspheres were investigated. The in-vitro release studies were performed in pH 7.4 phosphate buffer solution. For determining the effectiveness of microspheres in the treatment of brain oedema, Sprague-Dawley rats weighing 200-250g were used as an animal model. Brain oedema was generated by the cold lesion method, and the effectiveness of the microspheres in treatment of oedema was investigated by the wet-dry weight method, lipid peroxidation ratios and histological evaluations. The average particle size of the microspheres was 13.04 +/- 2.05 microm, and the in-vitro release time of the microspheres was 8 h for 100/release. The degree of oedema was significantly different from the control group for the wet-dry weight method and lipid peroxidation ratio (p < 0.05). Similarly, histological evaluation of the tissues shoved that degree of oedema was significantly decreased with respect to the control group. All these results showed that implantation of microspheres was significantly more effective with respect to the systemic administration of DSP.

Spectrophotometric determination of samarium(III) with chrome azurol S in the presence of cetylpyridinium chloride.

A sensitive, simple method for the determination of trace amounts of samarium by spectrophotometry is described based on the formation of the samarium-chrome azurol S (CAS) complex in micellar medium. The molar absorptivities of the complexes at pH 7.5 at 505 nm were 3.6x10(4) and 1.4x10(5) l mol(-1) cm(-1) for water media and cetylpyridinium chloride (CPC), respectively. Beer's law is obeyed from 0.05-2 mg l(-1) of samarium at 505 nm as Sm-CAS-CPC complex. Optimal conditions such as reagent amounts, and pH for the samarium determination were reported. The effects of foreign ions were also investigated. The proposed method was successfully applied to the determination of samarium contents in synthetic samples.