• Haemocystidium spp., a species complex infecting ancient aquatic turtles of the family Podocnemididae: First report of these parasites in Podocnemis vogli from the Orinoquia

      González, LP; Pacheco, MA; Escalante, AA; Jiménez Maldonado, AD; Cepeda, AS; Rodríguez-Fandiño, OA; Vargas‐Ramírez, M; Matta, NE (2019-12-01)
      © 2019 The Authors The genus Haemocystidium was described in 1904 by Castellani and Willey. However, several studies considered it a synonym of the genera Plasmodium or Haemoproteus. Recently, molecular evidence has shown the existence of a monophyletic group that corresponds to the genus Haemocystidium. Here, we further explore the clade Haemocystidium spp. by studying parasites from Testudines. A total of 193 individuals belonging to six families of Testudines were analyzed. The samples were collected in five localities in Colombia: Casanare, Vichada, Arauca, Antioquia, and Córdoba. From each individual, a blood sample was taken for molecular analysis, and peripheral blood smears were made, which were fixed and subsequently stained with Giemsa. The prevalence of Haemocystidium spp. was 1.55% (n = 3/193); all infected individuals belonged to Podocnemis vogli (Savanna Side-necked turtle) from the department of Vichada. This is the first report of Haemocystidium spp. in Colombia and in this turtle species. The phylogenetic analysis of a mitochondrial cytb fragment revealed Haemocystidium spp. as a monophyletic group and as a sister taxon of Haemoproteus catharti and the genus Plasmodium. Haemocystidium spp. are difficult to identify by morphology only. As a result, it is possible that some of the taxa, such as Haemocystidium (Simondia) pacayae, represent a species complex. The parasite found in our study is morphologically indistinguishable from Haemocystidium (Simondia) pacayae reported in Peru. However, the new lineage found in P. vogli shows a genetic distance of 0.02 with Hae. pacayae and 0.04 with Hae. peltocephali. It is proposed that this divergent lineage might be a new species. Nevertheless, additional molecular markers and ecological features could support this hypothesis in the future.
    • Harnessing a high cargo-capacity transposon for genetic applications in vertebrates

      Balciunas, D; Wangensteen, KJ; Wilber, A; Bell, J; Geurts, A; Sivasubbu, S; Wang, X; Hackett, PB; Largaespada, DA; McIvor, RS; Ekker, SC; Balciunas, Darius|0000-0003-1938-3243 (2006-11-01)
      Viruses and transposons are efficient tools for permanently delivering foreign DNA into vertebrate genomes but exhibit diminished activity when cargo exceeds 8 kilobases (kb). This size restriction limits their molecular genetic and biotechnological utility, such as numerous therapeutically relevant genes that exceed 8 kb in size. Furthermore, a greater payload capacity vector would accommodate more sophisticated cis cargo designs to modulate the expression and mutagenic risk of these molecular therapeutics. We show that the Tol2 transposon can efficiently integrate DNA sequences larger than 10 kb into human cells. We characterize minimal sequences necessary for transposition (miniTol2) in vivo in zebrafish and in vitro in human cells. Both the 8.5-kb Tol2 transposon and 5.8-kb miniTol2 engineered elements readily function to revert the deficiency of fumarylacetoacetate hydrolase in an animal model of hereditary tyrosinemia type 1. Together, Tol2 provides a novel nonviral vector for the delivery of large genetic payloads for gene therapy and other transgenic applications. © 2006 Balciunas et al.
    • Healthcare Options for People Experiencing Depression (HOPE∗D): The development and pilot testing of an encounter-based decision aid for use in primary care

      Barr, PJ; Forcino, RC; Dannenberg, MD; Mishra, M; Turner, E; Zisman-Ilani, Y; Matthews, J; Hinn, M; Bruce, M; Elwyn, G (2019-04-01)
      © © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. Objective To develop and pilot an encounter-based decision aid (eDA) for people with depression for use in primary care. Design We developed an eDA for depression through cognitive interviews and pilot tested it using a one-group pretest, post-Test design in primary care. Feasibility, fidelity of eDA use and acceptability were assessed using recruitment rates and semistructured interviews with patients, medical assistants and clinicians. Treatment choice and shared decision-making (SDM) were also assessed. Setting Interviews with adult patients and the public were conducted in a mall and library in Grafton County, New Hampshire, while clinician interviews took place by phone or at the clinician's office. Pilot testing occurred in a New Hampshire primary care practice. Participants Cognitive interviews were conducted with adults, ≥18 years, who could read English from the following stakeholder groups: history of depression, the public and clinicians. Patients with a Patient Health Questionnaire-9 score of ≥5 were recruited for piloting. Results Three stages of cognitive interviews were conducted (n=28). Changes to eDA included moving the combination therapy information and access to treatment information, adding colour, modifying pictograms and editing the talk-Therapy description. Clinician concerns about patient health literacy were not reflected in patient interviews. Of 59 patients who reviewed study information, 56 were eligible and agreed to participate in pilot testing; however, only 29 could be reached for follow-up. The eDA was widely accepted, though clinicians did not always use it as intended. We found no impact of eDA use on SDM, though patients chose a wider range of treatment options. Conclusions We demonstrated the feasibility of the use of an eDA for depression in primary care that was widely accepted. Further research is needed to improve the fidelity with which the eDA is used and to assess its impact on SDM and related health outcomes.
    • Heightened fire probability in Indonesia in non-drought conditions: the effect of increasing temperatures

      Fernandes, Kátia; Verchot, Louis; Baethgen, Walter; Gutiérrez-Vélez, Víctor Hugo; Pinedo-Vásquez, Miguel; Martius, Christopher (2017-04-27)
      In Indonesia, drought driven fires occur typically during the warm phase of the El Niño Southern Oscillation. This was the case of the events of 1997 and 2015 that resulted in months-long hazardous atmospheric pollution levels in Equatorial Asia and record greenhouse gas emissions. Nonetheless, anomalously active fire seasons have also been observed in non-drought years. In this work, we investigated the impact of temperature on fires and found that when the July-October (JASO) period is anomalously dry, the sensitivity of fires to temperature is modest. In contrast, under normal-to-wet conditions, fire probability increases sharply when JASO is anomalously warm. This describes a regime in which an active fire season is not limited to drought years. Greater susceptibility to fires in response to a warmer environment finds support in the high evapotranspiration rates observed in normal-to-wet and warm conditions in Indonesia. We also find that fire probability in wet JASOs would be considerably less sensitive to temperature were not for the added effect of recent positive trends. Near-term regional climate projections reveal that, despite negligible changes in precipitation, a continuing warming trend will heighten fire probability over the next few decades especially in non-drought years. Mild fire seasons currently observed in association with wet conditions and cool temperatures will become rare events in Indonesia.
    • Helicity-dependent photocurrents in the chiral Weyl semimetal RhSi

      Rees, D; Manna, K; Lu, B; Morimoto, T; Borrmann, H; Felser, C; Moore, JE; Torchinsky, DH; Orenstein, J; Torchinsky, Darius H|0000-0001-6497-2237 (2020-07-01)
      Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). Weyl semimetals are crystals in which electron bands cross at isolated points in momentum space. Associated with each crossing point (or Weyl node) is a topological invariant known as the Berry monopole charge. The circular photogalvanic effect (CPGE), whereby circular polarized light generates a helicity-dependent photocurrent, is a notable example of a macroscopic property that emerges directly from the topology of the Weyl semimetal band structure. Recently, it was predicted that the amplitude of the CPGE associated with optical transitions near a Weyl node is proportional to its monopole charge. In chiral Weyl systems, nodes of opposite charge are nondegenerate, opening a window of wavelengths where the CPGE resulting from uncompensated Berry charge can emerge. Here, we report measurements of CPGE in the chiral Weyl semimetal RhSi, revealing a CPGE response in an energy window that closes at 0.65 eV, in agreement with the predictions of density functional theory.
    • Hepatocystin is Essential for TRPM7 Function during Early Embryogenesis

      Overton, JD; Komiya, Y; Mezzacappa, C; Nama, K; Cai, N; Lou, L; Fedeles, SV; Habas, R; Runnels, LW (2015-12-16)
      Mutations in protein kinase C substrate 80K-H (PRKCSH), which encodes for an 80 KDa protein named hepatocystin (80K-H, PRKCSH), gives rise to polycystic liver disease (PCLD). Hepatocystin functions as the noncatalytic beta subunit of Glucosidase II, an endoplasmic reticulum (ER)-resident enzyme involved in processing and quality control of newly synthesized glycoproteins. Patients harboring heterozygous germline mutations in PRKCSH are thought to develop renal cysts as a result of somatic loss of the second allele, which subsequently interferes with expression of the TRP channel polycystin-2 (PKD2). Deletion of both alleles of PRKCSH in mice results in embryonic lethality before embryonic day E11.5. Here, we investigated the function of hepatocystin during Xenopus laevis embryogenesis and identified hepatocystin as a binding partner of the TRPM7 ion channel, whose function is required for vertebrate gastrulation. We find that TRPM7 functions synergistically with hepatocystin. Although other N-glycosylated proteins are critical to early development, overexpression of TRPM7 in Xenopus laevis embryos was sufficient to fully rescue the gastrulation defect caused by loss of hepatocystin. We observed that depletion of hepatocystin in Xenopus laevis embryos decreased TRPM7 expression, indicating that the early embryonic lethality caused by loss of hepatocystin is mainly due to impairment of TRPM7 protein expression.
    • Heterogeneous ozone effects on the DNA methylome of bronchial cells observed in a crossover study

      Bind, MAC; Rubin, DB; Cardenas, A; Dhingra, R; Ward-Caviness, C; Liu, Z; Mirowsky, J; Schwartz, JD; Diaz-Sanchez, D; Devlin, RB; Rubin, Donald B.|0000-0001-7127-9262 (2020-12-01)
      © 2020, The Author(s). We used a randomized crossover experiment to estimate the effects of ozone (vs. clean air) exposure on genome-wide DNA methylation of target bronchial epithelial cells, using 17 volunteers, each randomly exposed on two separated occasions to clean air or 0.3-ppm ozone for two hours. Twenty-four hours after exposure, participants underwent bronchoscopy to collect epithelial cells whose DNA methylation was measured using the Illumina 450 K platform. We performed global and regional tests examining the ozone versus clean air effect on the DNA methylome and calculated Fisher-exact p-values for a series of univariate tests. We found little evidence of an overall effect of ozone on the DNA methylome but some suggestive changes in PLSCR1, HCAR1, and LINC00336 DNA methylation after ozone exposure relative to clean air. We observed some participant-to-participant heterogeneity in ozone responses.
    • High-Throughput Discovery and Evaluation of a General Catalytic Method for N-Arylation of Weakly Nucleophilic Sulfonamides

      Becica, Joseph; Hruszkewycz, Damian; Steves, Janelle; Elward, Jennifer; Leitch, David; Dobereiner, Graham; 0000-0001-6885-2021 (2019-06-09)
      Sulfonamides are poor nucleophiles in Pd C-N coupling catalysis, hindering synthesis of densely-functionalized N,N-diaryl sulfonamide motifs relevant to medicinal chemistry. Through targeted high-throughput experimentation (HTE), we have identified the Pd/AdBippyPhos catalyst system as an effective and general method to construct this difficult to access moiety. In particular, AdBippyPhos is critical for the installation of heteroaromatic groups. Computational steric parameterization of the investigated ligands reveals the potential importance of remote steric demand, where a large cone angle combined with an accessible Pd center is correlated to successful catalysts for C-N coupling reactions.
    • High-yield oil palm expansion spares land at the expense of forests in the Peruvian Amazon

      Gutiérrez-Vélez, Víctor Hugo; DeFries, Ruth; Pinedo-Vásquez, Miguel; Uriarte, María; Padoch, Christine; Baethgen, Walter; Fernandes, Katia; Lim, Yili (2011-12-22)
      High-yield agriculture potentially reduces pressure on forests by requiring less land to increase production. Using satellite and field data, we assessed the area deforested by industrial-scale high-yield oil palm expansion in the Peruvian Amazon from 2000 to 2010, finding that 72% of new plantations expanded into forested areas. In a focus area in the Ucayali region, we assessed deforestation for high- and smallholder low-yield oil palm plantations. Low-yield plantations accounted for most expansion overall (80%), but only 30% of their expansion involved forest conversion, contrasting with 75% for high-yield expansion. High-yield expansion minimized the total area required to achieve production but counter-intuitively at higher expense to forests than low-yield plantations. The results show that high-yield agriculture is an important but insufficient strategy to reduce pressure on forests. We suggest that high-yield agriculture can be effective in sparing forests only if coupled with incentives for agricultural expansion into already cleared lands.
    • Highly robust model of transcription regulator activity predicts breast cancer overall survival

      Dong, C; Liu, J; Chen, SX; Dong, T; Jiang, G; Wang, Y; Wu, H; Reiter, JL; Liu, Y; Wu, Huanmei|0000-0003-0346-6044 (2020-04-03)
      © 2020 The Author(s). Background: While several multigene signatures are available for predicting breast cancer prognosis, particularly in early stage disease, effective molecular indicators are needed, especially for triple-negative carcinomas, to improve treatments and predict diagnostic outcomes. The objective of this study was to identify transcriptional regulatory networks to better understand mechanisms giving rise to breast cancer development and to incorporate this information into a model for predicting clinical outcomes. Methods: Gene expression profiles from 1097 breast cancer patients were retrieved from The Cancer Genome Atlas (TCGA). Breast cancer-specific transcription regulatory information was identified by considering the binding site information from ENCODE and the top co-expressed targets in TCGA using a nonlinear approach. We then used this information to predict breast cancer patient survival outcome. Result: We built a multiple regulator-based prediction model for breast cancer. This model was validated in more than 5000 breast cancer patients from the Gene Expression Omnibus (GEO) databases. We demonstrated our regulator model was significantly associated with clinical stage and that cell cycle and DNA replication related pathways were significantly enriched in high regulator risk patients. Conclusion: Our findings demonstrate that transcriptional regulator activities can predict patient survival. This finding provides additional biological insights into the mechanisms of breast cancer progression.
    • Historical Shifts in Brazilian P. falciparum Population Structure and Drug Resistance Alleles

      Griffing, SM; Viana, GMR; Mixson-Hayden, T; Sridaran, S; Alam, MT; de Oliveira, AM; Barnwell, JW; Escalante, AA; Povoa, MM; Udhayakumar, V (2013-03-15)
      Previous work suggests that Brazilian Plasmodium falciparum has limited genetic diversity and a history of bottlenecks, multiple reintroductions due to human migration, and clonal expansions. We hypothesized that Brazilian P. falciparum would exhibit clonal structure. We examined isolates collected across two decades from Amapá, Rondônia, and Pará state (n = 190). By examining more microsatellites markers on more chromosomes than previous studies, we hoped to define the extent of low diversity, linkage disequilibrium, bottlenecks, population structure, and parasite migration within Brazil. We used retrospective genotyping of samples from the 1980s and 1990s to explore the population genetics of SP resistant dhfr and dhps alleles. We tested an existing hypothesis that the triple mutant dhfr mutations 50R/51I/108N and 51I/108N/164L developed in southern Amazon from a single origin of common or similar parasites. We found that Brazilian P. falciparum had limited genetic diversity and isolation by distance was rejected, which suggests it underwent bottlenecks followed by migration between sites. Unlike Peru, there appeared to be gene flow across the Brazilian Amazon basin. We were unable to divide parasite populations by clonal lineages and pairwise FST were common. Most parasite diversity was found within sites in the Brazilian Amazon, according to AMOVA. Our results challenge the hypothesis that triple mutant alleles arose from a single lineage in the Southern Amazon. SP resistance, at both the double and triple mutant stages, developed twice and potentially in different regions of the Brazilian Amazon. We would have required samples from before the 1980s to describe how SP resistance spread across the basin or describe the complex internal migration of Brazilian parasites after the colonization efforts of past decades. The Brazilian Amazon basin may have sufficient internal migration for drug resistance reported in any particular region to rapidly spread to other parts of basin under similar drug pressure.
    • History Lessons for a General Theory of Law and Technology

      Mandel, Gregory N. (2007)
      Studying how prior law and technology issues were handled, and particularly how they were sometimes mishandled, provides valuable lessons for responding to current and future law and technology issues as they arise. This contribution to a symposium on whether and to what extent there can be a general theory of law and technology focuses on lessons that can be learned from past responses to once-new legal issues created by technological advance. The history lessons do not provide a complete road map for responding to each new law and technology issue - such a guide is not achievable considering the variety of technological change. But the lessons do provide a number of useful guidelines for how to confront novel law and technology challenges. In this article, I propose three lessons: (1) that preexisting legal categories may no longer apply for new law and technology issues; (2) that decision-makers be careful to avoid being blinded by the marvels of new technology in deciding law and technology cases; and (3) that the types of new law and technology disputes can be unforeseeable. I contend that these guidelines are applicable across a wide variety of technologies, even those that we cannot presently conceive of.
    • HIV-1 associated dementia: Symptoms and causes

      Ghafouri, M; Amini, S; Khalili, K; Sawaya, BE (2006-05-19)
      Despite the use of highly active antiretroviral therapy (HAART), neuronal cell death remains a problem that is frequently found in the brains of HIV-1-infected patients. HAART has successfully prevented many of the former end-stage complications of AIDS, however, with increased survival times, the prevalence of minor HIV-1 associated cognitive impairment appears to be rising among AIDS patients. Further, HIV-1 associated dementia (HAD) is still prevalent in treated patients as well as attenuated forms of HAD and CNS opportunistic disorders. HIV-associated cognitive impairment correlates with the increased presence in the CNS of activated, though not necessarily HIV-1-infected, microglia and CNS macrophages. This suggests that indirect mechanisms of neuronal injury and loss/death occur in HIV/AIDS as a basis for dementia since neurons are not themselves productively infected by HIV-1. In this review, we discussed the symptoms and causes leading to HAD. Outcome from this review will provide new information regarding mechanisms of neuronal loss in AIDS patients. © 2006 Ghafouri et al; licensee BioMed Central Ltd.
    • HIV-1 Nef is released in extracellular vesicles derived from astrocytes: Evidence for Nef-mediated neurotoxicity

      Sami Saribas, A; Cicalese, S; Ahooyi, TM; Khalili, K; Amini, S; Sariyer, IK (2017-01-01)
      © The Author(s) 2017. Human immunodeficiency virus-Associated neurological disorders (HANDs) affect the majority of AIDS patients and are a significant problem among HIV-1-infected individuals who live longer because of combined anti-retroviral therapies. HIV-1 utilizes a number of viral proteins and subsequent cytokine inductions to unleash its toxicity on neurons. Among HIV-1 viral proteins, Nef is a small protein expressed abundantly in astrocytes of HIV-1-infected brains and has been suggested to have a role in the pathogenesis of HAND. In order to explore its effect in the central nervous system, HIV-1 Nef was expressed in primary human fetal astrocytes (PHFAs) using an adenovirus. Our results revealed that HIV-1 Nef is released in extracellular vesicles (EVs) derived from PHFA cells expressing the protein. Interestingly, HIV-1 Nef release in EVs was enriched significantly when the cells were treated with autophagy activators perifosine, tomaxifen, MG-132, and autophagy inhibitors LY294002 and wortmannin suggesting a novel role of autophagy signaling in HIV-1 Nef release from astrocytes. Next, Nef-carrying EVs were purified from astrocyte cultures and neurotoxic effects on neurons were analyzed. We observed that HIV-1 Nef-containing EVs were readily taken up by neurons as demonstrated by immunocytochemistry and immunoblotting. Furthermore, treatment of neurons with Nef-carrying EVs induced oxidative stress as evidenced by a decrease in glutathione levels. To further investigate its neurotoxic effects, we expressed HIV-1 Nef in primary neurons by adenoviral transduction. Intracellular expression of HIV-1 Nef caused axonal and neurite degeneration of neurons. Furthermore, expression of HIV-1 Nef decreased the levels of phospho-Tau while enhancing total tau in primary neurons. In addition, treatment of primary neurons with Nef-carrying EVs suppressed functional neuronal action potential assessed by multielectrode array studies. Collectively, these data suggested that HIV-1 Nef can be a formidable contributor to neurotoxicity along with other factors, which leads to HAND in HIV-1-infected AIDS patients.
    • HIV-Specific Probabilistic Models of Protein Evolution

      Nickle, DC; Heath, L; Jensen, MA; Gilbert, PB; Mullins, JI; Kosakovsky Pond, SL; Pond, Sergei L. Kosakovsky|0000-0003-4817-4029 (2007-12-01)
      Comparative sequence analyses, including such fundamental bioinformatics techniques as similarity searching, sequence alignment and phylogenetic inference, have become a mainstay for researchers studying type 1 Human Immunodeficiency Virus (HIV-1) genome structure and evolution. Implicit in comparative analyses is an underlying model of evolution, and the chosen model can significantly affect the results. In general, evolutionary models describe the probabilities of replacing one amino acid character with another over a period of time. Most widely used evolutionary models for protein sequences have been derived from curated alignments of hundreds of proteins, usually based on mammalian genomes. It is unclear to what extent these empirical models are generalizable to a very different organism, such as HIV-1-the most extensively sequenced organism in existence. We developed a maximum likelihood model fitting procedure to a collection of HIV-1 alignments sampled from different viral genes, and inferred two empirical substitution models, suitable for describing between-and within-host evolution. Our procedure pools the information from multiple sequence alignments, and provided software implementation can be run efficiently in parallel on a computer cluster. We describe how the inferred substitution models can be used to generate scoring matrices suitable for alignment and similarity searches. Our models had a consistently superior fit relative to the best existing models and to parameter-rich data-driven models when benchmarked on independent HIV-1 alignments, demonstrating evolutionary biases in amino-acid substitution that are unique to HIV, and that are not captured by the existing models. The scoring matrices derived from the models showed a marked difference from common amino-acid scoring matrices. The use of an appropriate evolutionary model recovered a known viral transmission history, whereas a poorly chosen model introduced phylogenetic error. We argue that our model derivation procedure is immediately applicable to other organisms with extensive sequence data available, such as Hepatitis C and Influenza A viruses. © 2007 Nickle et al.
    • Home-based neurologic music therapy for arm hemiparesis following stroke: results from a pilot, feasibility randomized controlled trial

      Street, Alexander J.; Magee, Wendy L.; Bateman, Andrew; Parker, Michael; Odell-Miller, Helen; Fachner, Jörg; Magee|0000-0003-4350-1289 (2018-01-01)
      Objective: To assess the feasibility of a randomized controlled trial to evaluate music therapy as a home-based intervention for arm hemiparesis in stroke. Design: A pilot feasibility randomized controlled trial, with cross-over design. Randomization by statistician using computer-generated, random numbers concealed in opaque envelopes. Setting: Participants’ homes across Cambridgeshire, UK. Subjects: Eleven people with stroke and arm hemiparesis, 3–60 months post stroke, following discharge from community rehabilitation. Interventions: Each participant engaged in therapeutic instrumental music performance in 12 individual clinical contacts, twice weekly for six weeks. Main measures: Feasibility was estimated by recruitment from three community stroke teams over a 12-month period, attrition rates, completion of treatment and successful data collection. Structured interviews were conducted pre and post intervention to establish participant tolerance and preference. Action Research Arm Test and Nine-hole Peg Test data were collected at weeks 1, 6, 9, 15 and 18, pre and post intervention by a blinded assessor. Results: A total of 11 of 14 invited participants were recruited (intervention n = 6, waitlist n = 5). In total, 10 completed treatment and data collection. Conclusion: It cannot be concluded whether a larger trial would be feasible due to unavailable data regarding a number of eligible patients screened. Adherence to treatment, retention and interview responses might suggest that the intervention was motivating for participants. Trial registration: ClinicalTrials.gov identifier NCT 02310438.
    • Home-based neurologic music therapy for upper limb rehabilitation with stroke patients at community rehabilitation stage—a feasibility study protocol

      Street, Alexander J.; Magee, Wendy L.; Odell-Miller, Helen; Bateman, Andrew; Fachner, Jörg; Magee|0000-0003-4350-1289 (2015-09-23)
      Background: Impairment of upper limb function following stroke is more common than lower limb impairment and is also more resistant to treatment. Several lab-based studies with stroke patients have produced statistically significant gains in upper limb function when using musical instrument playing and techniques where rhythm acts as an external time-keeper for the priming and timing of upper limb movements. Methods: For this feasibility study a small sample size of 14 participants (3–60 months post stroke) has been determined through clinical discussion between the researcher and study host in order to test for management, feasibility and effects, before planning a larger trial determined through power analysis. A cross-over design with five repeated measures will be used, whereby participants will be randomized into either a treatment (n = 7) or wait list control (n = 7) group. Intervention will take place twice weekly over 6 weeks. The ARAT and 9HPT will be used to measure for quantitative gains in arm function and finger dexterity, pre/post treatment interviews will serve to investigate treatment compliance and tolerance. A lab based EEG case comparison study will be undertaken to explore audio-motor coupling, brain connectivity and neural reorganization with this intervention, as evidenced in similar studies. Discussion: Before evaluating the effectiveness of a home-based intervention in a larger scale study, it is important to assess whether implementation of the trial methodology is feasible. This study investigates the feasibility, efficacy and patient experience of a music therapy treatment protocol comprising a chart of 12 different instrumental exercises and variations, which aims at promoting measurable changes in upper limb function in hemiparetic stroke patients. The study proposes to examine several new aspects including home-based treatment and dosage, and will provide data on recruitment, adherence and variability of outcomes.
    • Homeostasis model assessment to detect insulin resistance and identify patients at high risk of breast cancer development: National Cancer Institute of Naples experience

      Capasso, I; Esposito, E; Pentimalli, F; Montella, M; Crispo, A; Maurea, N; D'Aiuto, M; Fucito, A; Grimaldi, M; Cavalcanti, E; Esposito, G; Brillante, G; Lodato, S; Pedicini, T; D'Aiuto, G; Ciliberto, G; Giordano, A; Giordano, Antonio|0000-0002-5959-016X (2013-03-18)
      Background: Metabolic Syndrome (MS) has been correlated to breast carcinogenesis. MS is common in the general population (34%) and increases with age and body mass index. Although the link between obesity, MS and hormone related cancer incidence is now widely recognized, the molecular mechanisms at the basis of such increase are still poorly characterized. A crucial role is supposed to be played by the altered insulin signalling, occurring in obese patients, which fuels cancer cell growth, proliferation and survival. Therefore we focused specifically on insulin resistance to investigate clinically the potential role of insulin in breast carcinogenesis. Methods. 975 patients were enrolled and the association between MS, insulin resistance, and breast cancer was evaluated. Women were stratified by age and menopausal status. Insulin resistance was measured through the Homeostasis Model Assessment score (HOMA-IR). The cut off value to define insulin resistance was HOMA-IR ≥ 2.50. Results: Higher prevalence of MS (35%) was found among postmenopausal women with breast cancer compared to postmenopausal healthy women (19%) [OR 2.16]. A broad range of BMI spanning 19-48 Kg/m§ssup§2§esup§ was calculated. Both cases and controls were characterized by BMI ≥ 25 Kg/m§ssup§2§esup§ (58% of cases compared to 61% of controls). Waist circumference >88 cm was measured in 53% of cases - OR 1.58- (95% CI 0.8-2.8) and in 46% of controls. Hyperinsulinemia was detected in 7% of cases - OR 2.14 (95% CI 1.78-2.99) and only in 3% of controls. HOMA-IR score was elevated in 49% of cases compared to 34% of controls [OR 1.86], suggesting that insulin resistance can nearly double the risk of breast cancer development. Interestingly 61% of women operated for breast cancer (cases) with HOMA-IR ≥ 2.5 presented subclinical insulin resistance with fasting plasma glucose levels and fasting plasma insulin levels in the normal range. Both android fat distribution and insulin resistance correlated to MS in the subgroup of postmenopausal women affected by breast cancer. Conclusions: Our results further support the hypothesis that MS, in particular insulin resistance and abdominal fat, can be considered as risk factors for developing breast cancer after menopause. We suggest that HOMA-IR, rather than fasting plasma glucose and fasting plasma insulin levels alone, could be a valuable tool to identify patients with subclinical insulin resistance, which could be relevant for primary prevention and for high risk patient screening. © 2013 Capasso et al.; licensee BioMed Central Ltd.
    • Host genetics and population structure effects on parasitic disease

      Williams-Blangero, S; Criscione, CD; VandeBerg, JL; Correa-Oliveira, R; Williams, KD; Subedi, J; Kent, JW; Williams, J; Kumar, S; Blangero, J (2012-01-01)
      Host genetic factors exert significant influences on differential susceptibility to many infectious diseases. In addition, population structure of both host and parasite may influence disease distribution patterns. In this study, we assess the effects of population structure on infectious disease in two populations in which host genetic factors influencing susceptibility to parasitic disease have been extensively studied. The first population is the Jirel population of eastern Nepal that has been the subject of research on the determinants of differential susceptibility to soil-transmitted helminth infections. The second group is a Brazilian population residing in an area endemic for Trypanosoma cruzi infection that has been assessed for genetic influences on differential disease progression in Chagas disease. For measures of Ascaris worm burden, within-population host genetic effects are generally more important than host population structure factors in determining patterns of infectious disease. No significant influences of population structure on measures associated with progression of cardiac disease in individuals who were seropositive for T. cruzi infection were found.