Treatment of Depression in Huntington's Disease: A Systematic Review.

Depression is a common psychiatric disorder among individuals with Huntington's disease (HD). Depression in HD and major depressive disorder appear to have different pathophysiological mechanisms. Despite the unique pathophysiology, the treatment of depression in HD is based on data from the treatment of major depressive disorder in the general population. The objective of this systematic review was to conduct a comprehensive evaluation of the available evidence. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Studies on the treatment of depression in HD were identified by searching MEDLINE, Embase, and PsycInfo. The initial search yielded 2,771 records, 41 of which were ultimately included. There were 19 case reports, seven case series, three cross-sectional studies, one qualitative study, nine nonrandomized studies, and two randomized trials among the included studies. The most common assessment tools were the Hospital Anxiety and Depression Scale (N=8), the Beck Depression Inventory (N=6), and the Hamilton Depression Rating Scale (N=6). Only 59% of the included studies assessed depressive symptoms with a scoring system. The pharmacological options for the treatment of depression included antidepressants and antipsychotics. Nonpharmacological approaches were multidisciplinary rehabilitation, psychotherapy, and neurostimulation. Limited evidence on the treatment of depression in HD was available, and this literature consisted mainly of case reports and case series. This systematic review highlights the knowledge gap and the pressing need for HD-specific research to determine the efficacy of treatment approaches for depression in HD.

Prion Dissemination through the Environment and Medical Practices: Facts and Risks for Human Health.

Prion diseases are a group of fatal, infectious neurodegenerative disorders affecting various species of mammals, including humans. The infectious agent in these diseases, termed prion, is composed exclusively of a misfolded protein that can spread and multiply in the absence of genetic materials. In this article, we provide an overview of the mechanisms of prion replication, interindividual transmission, and dissemination in communities. In particular, we review the potential role of the natural environment in prion transmission, including the mechanisms and pathways for prion entry and accumulation in the environment as well as its roles in prion mutation, adaptation, evolution, and transmission. We also discuss the transmission of prion diseases through medical practices, scientific research, and use of biological products. Detailed knowledge of these aspects is crucial to limit the spreading of existing prion diseases as well as to prevent the emergence of new diseases with possible catastrophic consequences for public health.

North American and Norwegian Chronic Wasting Disease Prions Exhibit Different Potential for Interspecies Transmission and Zoonotic Risk.

BACKGROUND: Chronic wasting disease (CWD) is a rapidly spreading prion disorder affecting various species of wild and captive cervids. The risk that CWD poses to cohabiting animals or more importantly to humans is largely unknown. METHODS: In this study, we investigated differences in the capacity of CWD isolates obtained from 6 different cervid species to induce prion conversion in vitro by protein misfolding cyclic amplification. We define and quantify spillover and zoonotic potential indices as the efficiency by which CWD prions sustain prion generation in vitro at expenses of normal prion proteins from various mammals and human, respectively. RESULTS: Our data suggest that reindeer and red deer from Norway could be the most transmissible CWD prions to other mammals, whereas North American CWD prions were more prone to generate human prions in vitro. CONCLUSIONS: Our results suggest that Norway and North American CWD prions correspond to different strains with distinct spillover and zoonotic potentials.

Microsolvation of F.

A staggering structural diversity for the microsolvation of F- with up to six water molecules is uncovered in this work. Given the structural variety and the proximity in energy among several local minima, we show here that in order to match available experimental data, statistical averages over contributing structures are needed, rather than assigning experimental values to isolated structures. Our results suggest that the formal charge in F- is strong enough as to induce partial and total dissociation of water molecules and to alter the nature of the surrounding network of water to water hydrogen bonds. We provide an extensive analysis of bonding interactions under the NBO and QTAIM formalisms, our main results suggest a complex interplay between ionic and covalent characters for the FH interactions as a function of the separation between the atoms.

Development of a methodology for large-scale production of prions for biological and structural studies.

Prion diseases are a group of infectious neurodegenerative diseases produced by the conversion of the normal prion protein (PrPC) into the disease-associated form (PrPSc). Extensive evidence indicate that the main or sole component of the infectious agent is PrPSc, which can replicate in affected individuals in the absence of nucleic acids. However, the mechanism of PrPC-to-PrPSc conversion remains elusive, which has been attributed to the lack of sufficient structural information of infectious PrPSc and a reliable system to study prion replication in vitro. In this article we adapted the Protein Misfolding Cyclic Amplification (PMCA) technology for rapid and efficient generation of highly infectious prions in large-scale. Murine prions of the RML strain were efficiently propagated in volumes up to 1,000-fold larger than conventional PMCA. The large-scale PMCA (LS-PMCA) procedure enabled to produce highly infectious prions, which maintain the strain properties of the seed used to begin the reaction. LS-PMCA was shown to work with various species and strains of prions, including mouse RML and 301C strains, hamster Hyper prion, cervid CWD prions, including a rare Norwegian CWD prion, and human CJD prions. We further improved the LS-PMCA into a bioreactor format that can operate under industry-mimicking conditions for continuous and unlimited production of PrPSc without the need to keep adding brain-derived prions. In our estimation, this bioreactor can produce in 1d an amount of prions equivalent to that present in 25 infected animals at the terminal stage of the disease. Our LS-PMCA technology may provide a valuable tool to produce large quantities of well-defined and homogeneous infectious prions for biological and structural studies.

Detection of prions in the urine of patients affected by sporadic Creutzfeldt-Jakob disease.

OBJECTIVE: Currently, it is unknown whether infectious prions are present in peripheral tissues and biological fluids of patients affected by sporadic Creutzfeldt-Jakob disease (sCJD), the most common prion disorder in humans. This represents a potential risk for inter-individual prion infection. The main goal of this study was to evaluate the presence of prions in urine of patients suffering from the major subtypes of sCJD. METHODS: Urine samples from sCJD patients spanning the six major subtypes were tested. As controls, we used urine samples from people affected by other neurological or neurodegenerative diseases as well as healthy controls. These samples were analyzed blinded. The presence of prions was detected by a modified version of the PMCA technology, specifically optimized for high sensitive detection of sCJD prions. RESULTS: The PMCA assay was first optimized to detect low quantities of prions in diluted brain homogenates from patients affected by all subtypes of sCJD spiked into healthy urine. Twenty-nine of the 81 patients affected by sCJD analyzed in this study were positive by PMCA testing, whereas none of the 160 controls showed any signal. These results indicate a 36% sensitivity and 100% specificity. The subtypes with the highest positivity rate were VV1 and VV2, which combined account for about 15-20% of all sCJD cases, and no detection was observed in MV1 and MM2. INTERPRETATION: Our findings indicate that potentially infectious prions are secreted in urine of some sCJD patients, suggesting a possible risk for inter-individual transmission. Prion detection in urine might be used as a noninvasive preliminary screening test to detect sCJD.

Community-embedded disease intervention specialist program for syphilis partner notification in a clinic serving men who have sex with men.

BACKGROUND/OBJECTIVES: We evaluated the effectiveness of a Community-Embedded Disease Intervention Specialist (CEDIS) in providing partner notification (PN) for primary syphilis cases in a high STD morbidity, community-based clinic serving men who have sex with men in Los Angeles. METHODS: The CEDIS was trained by the same standards as the local health department Disease Investigator Specialists but was employed by and stationed at the clinic where the primary cases were diagnosed. We compared the CEDIS on specific PN outcomes before and after placement of the CEDIS and among countywide men who have sex with men primary syphilis cases, excluding the cases from the CEDIS clinic. RESULTS: In 2009-2010 after placement of the CEDIS, 100% (87) of primary cases assigned were interviewed; 28% (26) on the same day as their clinic visit and 64% (59) within 7 days. In 2006-2007 before placement of the CEDIS, 67% (43) of primary cases assigned were interviewed; only 2% (1) were interviewed within 7 days. In 2009-2010 countywide, 9% (21) of 252 primary cases assigned were interviewed on the same day as their clinic visit; 18% (45) within 7 days. After placement of the CEDIS, 15% (21) of 140 partners elicited were identified with early syphilis and brought to treatment compared with 0% of 13 partners elicited before placement of the CEDIS, and 15% (25) of 171 partners elicited countywide. CONCLUSION: The CEDIS program fosters key elements to a successful PN program, such as prompt interviewing of newly diagnosed cases and community trust.

Hepatitis C: seroprevalencia en niños politransfundidos / Hepatiris C: seroprevalence in politransfused children

Se realizó un estudio prospectivo entre abril y septiembre de 1993, donde se estudiaron 50 niños politransfundidos pertenecientes a las consultas de hematología Pediátrica, Pediatría Médica Quirúrgica y Neonatal del Hospital "Dr. Domingo Luciani" (HDL), IVSS, El Llanito, Edo. Miranda-Venezuela. Se incluyeron niños de ambos sexos, en edades comprendidas entre tres meses y diecisiete años y que hubiesen recibido la última transfusión tres meses (90 días) antes de ser incluídos en el trabajo. Los pacientes fueron divididos en dos grupos: Grupo Pre-despistaje: en el que se incluyeron aquellos niños que recibieron la última transfusión antes de la implementación del despistaje serológico para VHC en el Banco de Sangre del HDL. Grupo Post-despistaje: constituido por los niños que recibieron su última transfusión después de la implementación de este método. La investigación de anticuerpos séricos anti-VHC se realizó por medio de la Técnica de Inmunoensayo Enzimático con Kit de segunda generación (ELISA-2), por metodología recombinante de laboratorios Abbott. Se evidenció predominio del sexo masculino (72 por ciento), los pacientes recibieron un total de 532 unidades de hemoderivados, siendo el Concentrado Globular el más frecuentemente transfundido, las enfermedades hematológicas constituyeron el 80 por ciento de los diagnósticos primarios. Dieciocho niños pertenecían al primer grupo y 32 al segundo; encontrando que 11 por ciento (2 pacientes) y 3 por ciento (1 paciente) fueron seropositivos para VHC en cada grupo respectivamente: esta diferencia no fue estadísticamente significativa