Comparison of [11C]UCB-J and [18F]FDG PET in Alzheimer’s disease: A tracer kinetic modeling study

[¹¹C]UCB-J PET for synaptic vesicle glycoprotein 2 A (SV2A) has been proposed as a suitable marker for synaptic density in Alzheimer’s disease (AD). We compared [¹¹C]UCB-J binding for synaptic density and [¹⁸F]FDG uptake for metabolism (correlated with neuronal activity) in 14 AD and 11 cognitively normal (CN) participants. We assessed both absolute and relative outcome measures in brain regions of interest, i.e., K₁ or R₁ for [¹¹C]UCB-J perfusion, V_T (volume of distribution) or DVR to cerebellum for [¹¹C]UCB-J binding to SV2A; and K_i or K_iR to cerebellum for [¹⁸F]FDG metabolism. [¹¹C]UCB-J binding and [¹⁸F]FDG metabolism showed a similar magnitude of reduction in the medial temporal lobe of AD –compared to CN participants. However, the magnitude of reduction of [¹¹C]UCB-J binding in neocortical regions was less than that observed with [¹⁸F]FDG metabolism. Inter-tracer correlations were also higher in the medial temporal regions between synaptic density and metabolism, with lower correlations in neocortical regions. [¹¹C]UCB-J perfusion showed a similar pattern to [¹⁸F]FDG metabolism, with high inter-tracer regional correlations. In summary, we conducted the first in vivo PET imaging of synaptic density and metabolism in the same AD participants and reported a concordant reduction in medial temporal regions but a discordant reduction in neocortical regions.     

Safety of anticoagulation therapy in well-informed older patients

BACKGROUND: In older populations, oral anticoagulation therapy (OAT) is underused by physicians, mainly because of fear of bleeding complications. The aim of this study was to determine the incidence of bleeding complications and associated risk factors in a large heterogeneous group of older patients. METHODS: Combined retrospective and prospective cohort study conducted in geriatric and internal medicine departments. All patients 80 years or older discharged with the recommendation of OAT were followed up for a mean +/- SD of 28.8 +/- 36.3 months. The rate of bleeding events and the quality of anticoagulation were compared across a wide range of demographic and clinical variables and cognitive and functional status. In addition, we assessed the quality of education given to the patient or caregiver on the use of OAT. RESULTS: Among 15 387 patients 80 years or older, 323 (2.1%) were discharged with the recommendation of OAT. The rate of major bleedings was 2.4 events per 1000 patient-months. Socioeconomic and cognitive variables and functional impairments were not associated with an increased rate of bleeding. In multivariate analysis, insufficient education on OAT as perceived by the patient or caregiver (odds ratio [OR], 8.83), polypharmacy (OR, 6.14), and international normalized ratio values above the therapeutic range (OR, 1.08) were the only significant predictive factors for bleeding complications. CONCLUSIONS: The rate of bleeding complications, especially major bleedings, was low in this large group of older patients, many with comorbidities and cognitive and functional impairments. Insufficient OAT education was the major factor that predicted bleeding. Therefore, improving and fostering better methods of OAT education may further reduce bleeding complications.     

Transition to Retirement of 1990s Immigrants from the Former Soviet Union to Israel

The purpose of the current research was to compare pre- and post-retirement financial and economic resources of two groups of Jewish Israelis, Russian-speaking immigrants from the Former Soviet Union (FSU) and Hebrew-speaking veteran Israelis. The strategy of data-processing was based on SHARE Wave 6 (Survey of Health, Ageing and Retirement in Europe) and included two levels of analysis: a) household general economic indices and b) individual economic variables for two age subsamples (’51–66’ and ‘67?+?’). The research-based model of well-being enabled comparison of economic profiles of the studied groups. The results of logistic regression and discriminant analysis of twenty SHARE 6.0 monetary variables displayed economic and financial inequality of retirement resources between veteran Israeli residents and Russian-speaking immigrants. Lower values of main residence, owned vehicles, and private pensions, together with higher values of mortgage burden, rent expenses, and inter-family support were significant distinguishing features of FSU immigrants. Analysis of the household indices demonstrated that the group of older FSU immigrants was most vulnerable due to their lowest values of household net worth and total income. According to the results of inter- and intra-gender comparisons of incomes between the groups of ‘67?+?’ representatives, Russian-speaking women were identified as having the fewest resources. The retirement resources of Russian-speaking Israelis were clearly inferior to those of Hebrew-speaking veteran Israelis of the same age.

Future research of retirement resources of Israelis may include non-financial components of human capital and additional socio-demographic factors.

     

Musashi 2 (MSI2) expression as an independent prognostic biomarker in non-small cell lung cancer (NSCLC)

BackgroundMusashi-2 (MSI2) is a member of RNA-binding protein family that regulates mRNA translation of numerous intracellular targets and influences maintenance of stem cell identity. This study assessed MSI2 as a potential clinical biomarker in non-small cell lung cancer (NSCLC).MethodsThe current study included 40 patients with NSCLC, of whom one presented with stage 1, 14 presented with stage II, 15 presented with stage III, and 10 patients had stage IV. All patients received standard of care treatments. All patient samples were obtained before treatment started. We used immunohistochemical (IHC) approach to measure MSI2 protein expression in matching specimens of normal lung versus tumor tissues, and primary versus metastatic tumors, followed by correlative analysis in relation to clinical outcomes. In parallel, clinical correlative analysis of MSI2 mRNA expression was performed in silico using publicly available datasets (TCGA/ICGC and KM plots).ResultsMSI2 protein expression in patient samples was significantly elevated in NSCLC primary tumors versus normal lung tissue (P=0.03). MSI2 elevated expression positively correlated with a decreased progression free survival (PFS) (P=0.026) combined for all stages and with overall survival (OS) at stage IV (P=0.013). Elevated MSI2 expression on RNA level was confirmed in primary tumor versus normal tissue samples in TCGA dataset (P<0.0001), and positively correlated with decreased OS (P=0.02). No correlation was observed between MSI2 expression and age, sex, smoking, and treatment type.ConclusionsElevated MSI2 expression in primary NSCLC tumors is associated with poor prognosis and can be used as a novel potential prognostic biomarker in NSCLC patients. Future studies in an extended patient cohort are warranted.     

AUDITORY EVOKED POTENTIALS EVIDENCE FOR DIFFERENCES IN INFORMATION PROCESSING BETWEEN HIGH AND LOW HYPNOTIZABLE SUBJECTS

N100 and P300 auditory evoked potentials in 2-stimulus oddball paradigm were analyzed in high (HH, n = 18) and low (LH, n = 15) hypnotizable participants under waking condition. LH subjects committed more errors than HH subjects. HH subjects demonstrated shorter N100 latencies at frontal electrodes and significant N100 differences between target and nontarget stimuli (higher N100 amplitude and increased latency at parietal sites to targets vs. nontargets), whereas LH subjects failed to show any differences. The overall increase of P300 amplitude with frontal-central localization of P300 maximum was found in HH subjects compared to LH subjects. The obtained results support the psychophysiological model of HH individuals having more effective frontal attentional systems involved in detecting, integrating, and filtering relevant information.     

COMT Genotype and Sensory and Sensorimotor Gating in High and Low Hypnotizable Subjects

We investigated the association between hypnotizability, COMT polymorphism, P50 suppression ratio, and prepulse inhibition of acoustic startle response (ASR) in 21 high (HH) and 19 low (LH) hypnotizable subjects. The frequency of Met/Met carriers of COMT polymorphysm was higher in HH than in LH group (33.3% versus 10.6%, p = .049). Increased ASR amplitude and latency and decreased prepulse inhibition at 120 ms lead interval were found in the HH compared to the LH group. The effect of COMT genotype on prepulse inhibition was observed in LH group only. No between-group differences in P50 measures were found. The obtained results suppose the participation of dopamine system in mechanisms of hypnotizability and different allocation of attentional resources in HH and LH subjects.     

Vitamin D receptor gene polymorphisms modulate the skeletal response to vitamin D supplementation in healthy girls

ObjectivesVitamin D receptor (VDR) gene plays an important role in bone mass regulation. We have previously shown a beneficial effect of vitamin D supplementation on bone mass in girls. This study investigated whether the musculo-skeletal response to Vitamin D was modulated by polymorphisms in VDR gene.DesignRandomized placebo-controlled trial.Methods179 girls (10–17 years), were randomly assigned to placebo or Vitamin D3 for one year. VDR genotypes were determined in 167 girls using BsmI, TaqI and ApaI restriction enzymes. Bone mass at the spine, hip, forearm and total body, and lean mass were measured by DXA at baseline and at one year.ResultsAfter one year, VDR gene polymorphisms using Bsm1 and TaqI restriction enzymes were associated with percent changes in bone area, BMC and BMD at multiple skeletal sites in the Vitamin D3 group but not in the placebo group. The least increments were observed in the BB and tt genotypes. No similar effect was observed with ApaI enzyme. This relationship between VDR genotypes and changes in BMD and BMC remained significant after adjustment for puberty, changes in lean mass, height and bone area.ConclusionVDR gene polymorphisms influence the skeletal response to vitamin D supplementation in healthy adolescent girls.     

An Analysis of Respondent Driven Sampling with Injection Drug Users (IDU) in Albania and the Russian Federation

Internet access has caused a global revolution in the way people of all ages and genders interact. Many have turned to the Internet to seek love, companionship, and sex, prompting researchers to move behavioral studies online. The sexual behavior of men who have sex with men (MSM) has been more closely studied than that of any other group online given the abundance of gay-oriented websites and concerns about increasing transmission of HIV and other sexually transmitted infections. Not only does the Internet provide a new medium for the conduct of behavioral research and for participant recruitment into an array of research studies, it has the as yet unrealized potential to reach huge numbers of MSM with innovative harm reduction and prevention messages tailored to individualized needs, interests, and risk behavior. Internet-based research on sexual behavior has many advantages in rapidity of recruitment of diverse samples which include individuals unreachable through conventional methods (i.e., non-gay identified and geographically and socially isolated MSM, etc.). Internet-based research also presents some new methodologic challenges in study design, participant recruitment, survey implementation, and interpretation of results. In addition, there are ethical issues unique to online research including difficulties in verifying informed consent, obstacles to surveying minors, and the ability to assure anonymity. This paper presents a review of Internet-based research on sexual behavior in MSM, a general discussion of the methodologic and ethical challenges of Internet-based research, and recommendations for future interdisciplinary research. Dr. Parsons is with the Center for HIV/AIDS Educational Studies and Training (CHEST), Hunter College and the Graduate Center of the City University of New York, NY; Dr. Tesoriero is with the Office of Program Evaluation and Research, New York State Department of Health AIDS Institute, Menands, NY; Dr. Carballo-Dieguez is with the HIV Center for Clinical and Behavioral Studies, New York State Psychiatric Institute and Columbia University, New York, NY; Dr. Remien is with the HIV Center for Clinical and Behavioral Studies, New York State Psychiatric Institute and Columbia University, New York, NY.