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Rationale & Objective In the general population, cognitive impairment is associated with increased mortality, and higher levels of education are associated with lower risks for cognitive impairment and mortality. These associations are not well studied in patients receiving long-term hemodialysis and were the focus of the current investigation. Study Design Prospective cohort study. Setting & Participants Adult hemodialysis patients treated in 20 Italian dialysis clinics. Exposures Patients’ cognitive function across 5 domains (memory, attention, executive function, language, and perceptual-motor function), measured using a neuropsychological assessment comprising 10 tests; and patients’ self-reported years of education. Outcome All-cause mortality. Analytical Approach Nested multivariable Cox regression models were used to examine associations of cognition (any domain impaired, number of domains impaired, and global function score from principal components analysis of unadjusted test scores) and education with mortality and whether there were interactions between them. Results 676 (70.6%) patients participated, with a median age of 70.9 years and including 38.8% women. Cognitive impairment was present in 79.4% (527/664; 95% CI, 76.3%-82.5%). During a median follow-up of 3.3 years (1,874 person-years), 206 deaths occurred. Compared to no cognitive impairment, adjusted HRs for mortality were 1.77 (95% CI, 1.07-2.93) for any impairment, 1.48 (95% CI, 0.82-2.68) for 1 domain impaired, 1.88 (95% CI, 1.01-3.53) for 2 domains, and 2.01 (95% CI, 1.14-3.55) for 3 to 5 domains. The adjusted HR was 0.68 (95% CI, 0.51-0.92) per standard deviation increase in global cognitive function score. Compared with primary or lower education, adjusted HRs were 0.79 (95% CI, 0.53-1.20) for lower secondary and 1.13 (95% CI, 0.80-1.59) for upper secondary or higher. The cognition-by-education interaction was not significant (P = 0.7). Limitations Potential selection bias from nonparticipation and missing data; no data for cognitive decline; associations with education were not adjusted for other socioeconomic factors. Conclusions Cognitive impairment is associated with premature mortality in hemodialysis patients. Education does not appear to be associated with mortality.

Hepatitis C virus (HCV) infection is a global public health problem. The implementation of public health interventions (PHI) to control HCV infection could effectively interrupt HCV transmission. PHI targeting high-risk populations, e.g., people who inject drugs (PWID), are the most efficient but there is a lack of tools for prioritizing individuals within a high-risk community. Here, we present Intelligent Network DisRuption Analysis (INDRA), a targeted strategy for efficient interruption of hepatitis C transmissions. Using a large HCV transmission network among PWID in Indiana as an example, we compare effectiveness of random and targeted strategies in reducing the rate of HCV transmission in two settings: (1) long-established and (2) rapidly spreading infections (outbreak). Identification of high centrality for the network nodes co-infected with HIV or >1 HCV subtype indicates that the network structure properly represents the underlying contacts among PWID relevant to the transmission of these infections. Changes in the network’s global efficiency (GE) were used as a measure of the PHI effects. In setting 1, simulation experiments showed that a 50% GE reduction can be achieved by removing 11.2 times less nodes using targeted vs random strategies. A greater effect of targeted strategies on GE was consistently observed when networks were simulated: (1) with a varying degree of errors in node sampling and link assignment, and (2) at different levels of transmission reduction at affected nodes. In simulations considering a 10% removal of infected nodes, targeted strategies were ~2.8 times more effective than random in reducing incidence. Peer-education intervention (PEI) was modeled as a probabilistic distribution of actionable knowledge of safe injection practices from the affected node to adjacent nodes in the network. Addition of PEI to the models resulted in a 2–3 times greater reduction in incidence than from direct PHI alone. In setting 2, however, random direct PHI were ~3.2 times more effective in reducing incidence at the simulated conditions. Nevertheless, addition of PEI resulted in a ~1.7-fold greater efficiency of targeted PHI. In conclusion, targeted PHI facilitated by INDRA outperforms random strategies in decreasing circulation of long-established infections. Network-based PEI may amplify effects of PHI on incidence reduction in both settings.

Background & Aims: The host genetic environment contributes significantly to the outcomes of hepatitis C virus (HCV) infection and therapy response, but little is known about any effects of HCV infection on the host beyond any changes related to adaptive immune responses. HCV persistence is associated strongly with mitochondrial dysfunction, with liver mitochondrial DNA (mtDNA) genetic diversity linked to disease progression. Methods: We evaluated the genetic diversity of 2 mtDNA genomic regions (hypervariable segments 1 and 2) obtained from sera of 116 persons using next-generation sequencing. Results: Results were as follows: (1) the average diversity among cases with seronegative acute HCV infection was 4.2 times higher than among uninfected controls; (2) the diversity level among cases with chronic HCV infection was 96.1 times higher than among uninfected controls; and (3) the diversity was 23.1 times higher among chronic than acute cases. In 2 patients who were followed up during combined interferon and ribavirin therapy, mtDNA nucleotide diversity decreased dramatically after the completion of therapy in both patients: by 100% in patient A after 54 days and by 70.51% in patient B after 76 days. Conclusions: HCV infection strongly affects mtDNA genetic diversity. A rapid decrease in mtDNA genetic diversity observed after therapy-induced HCV clearance suggests that the effect is reversible, emphasizing dynamic genetic relationships between HCV and mitochondria. The level of mtDNA nucleotide diversity can be used to discriminate recent from past infections, which should facilitate the detection of recent transmission events and thus help identify modes of transmission. Keywords: Disease Biomarkers, mtDNA, Noninvasive

Detection of Trichuris trichiura during colonoscopic examination is an unusual finding, at least in developed countries. We report a case of a coincidental endoscopic diagnosis of whipworm infestation performed in a patient referred to our open-access endoscopy even before a faecal examination for ova and/or parasites had been performed. Review of literature on colonoscopic diagnosis of T. trichuria is provided.

AN ABNORMAL POSTPRANDIAL TONIC AND PHASIC RECTO-SIGMOID MOTOR ACTIVITY IS EVIDENT IN PATIENTS WITH MIGRAINE AND IRRITABLE BOWEL SYNDROME M. Di Stefano ∗ ,1, E. Pucci 2, C. Mengoli 1 , F. Racca1 , G. Sandrini 2, G. Nappi2, G. Corazza1 1First Department of Medicine, University of Pavia, IRCCS S. Matteo Hospital Foundation, Pavia; 2University Centre for Adaptive Disorders and Headache (UCADH), University of Pavia, IRCCS “C. Mondino”, Pavia

The molecular structure of [Cp 2 Ti(THF) 2 ] [Co(CO) 4 ] has been determined by X-ray diffraction at −104 °C. The compound crystallizes in the acentric monoclinic space group P 2 1 with a = 7.812(4), b = 15.010(4), c = 28.445(9) A, β = 94.10(3)°, V = 3327.1 A 3 and Z = 6. The unique feature of this crystal structure is that there are three independent cation/anion pairs in the unit cell and that the structure of the Cp 2 Ti(THF) 2 + fragment is significantly different for each. The most significant difference lies in the OTiO angles which range from 77.2 to 82.9°. This result points out the magnitude of the effect that steric requirements due to crystal packing forces can have in determining structural features.

The multiple roles played by both the rhodium and alkoxide catalysts in the efficient and mild condensation of alcohols to higher molecular weight alcohols, the Guerbet reaction, have been clarified. Rhodium promotes alcohol dehydrogenation at the beginning of the reaction sequence, and later assists in the saturation of an allyl alcohol intermediate. The alkoxide catalyst pushes the intermediates through the reaction sequence by serving both as a simple base in the aldol condensation step, and as a hydride reducing agent for the various vinyl and carbonyl moieties found in the reaction intermediates. The investigation also revealed a strong rate dependence upon the initial alkoxide concentration and indicated how the presence of water, a primary Guerbet reaction product, leads to deactivation of the system.