Intranasal administration of acetylcholinesterase inhibitors

This short review outlines the rationale, challenges, and opportunities for intranasal acetylcholinesterases, in particular galantamine. An in vitro screening model facilitated the development of a therapeutically viable formulation. In vivo testing confirmed achievement of therapeutically relevant drug levels that matched or exceeded those for oral dosing, with a dramatic reduction in undesired emetic responses. Intranasal drug delivery is an effective option for the treatment of Alzheimer's disease and other central nervous system disorders

Measurement of stellar age from uranium decay

The ages of the oldest stars in the Galaxy indicate when star formation began, and provide a minimum age for the Universe. Radioactive dating of meteoritic material and stars relies on comparing the present abundance ratios of radioactive and stable nuclear species to the theoretically predicted ratios of their production. The radioisotope $^{232}$Th (half-life 14 Gyr) has been used to date Galactic stars, but it decays by only a factor of two over the lifetime of the Universe. $^{238}$U (half-life 4.5 Gyr) is in principle a more precise age indicator, but even its strongest spectral line, from singly ionized uranium at a wavelength of 385.957 nm, has previously not been detected in stars. Here we report a measurement of this line in the very metal-poor star CS31082-001, a star which is strongly overabundant in its heavy elements. The derived uranium abundance, log(U/H) = -13.7+/-0.14+/-0.12 yields an age of 12.5+/-3 Gyr, though this is still model dependent. The observation of this cosmochronometer gives the most direct age determination of the Galaxy. Also, with improved theoretical and laboratory data, it will provide a highly precise lower limit to the age of the Universe.Comment: 3 pages, 1 figure, 1 table, published in Natur

Response Prediction in Chronic Hepatitis C by Assessment of IP-10 and IL28B-Related Single Nucleotide Polymorphisms

Background: High baseline levels of IP-10 predict a slower first phase decline in HCV RNA and a poor outcome following interferon/ribavirin therapy in patients with chronic hepatitis C. Several recent studies report that single nucleotide polymorphisms (SNPs) adjacent to IL28B predict spontaneous resolution of HCV infection and outcome of treatment among HCV genotype 1 infected patients. Methods and Findings: In the present study, we correlated the occurrence of variants at three such SNPs (rs12979860, rs12980275, and rs8099917) with pretreatment plasma IP-10 and HCV RNA throughout therapy within a phase III treatment trial (HCV-DITTO) involving 253 Caucasian patients. The favorable SNP variants (CC, AA, and TT, respectively) were associated with lower baseline IP-10 (P = 0.02, P = 0.01, P = 0.04) and were less common among HCV genotype 1 infected patients than genotype 2/3 (P<0.0001, P<0.0001, and P = 0.01). Patients carrying favorable SNP genotypes had higher baseline viral load than those carrying unfavorable variants (P = 0.0013, P = 0.029, P = 0.0004 respectively). Among HCV genotype 1 infected carriers of the favorable C, A, or T alleles, IP-10 below 150 pg/mL significantly predicted a more pronounced reduction of HCV RNA from day 0 to 4 (first phase decline), which translated into increased rates of RVR (62%, 53%, and 39%) and SVR (85%, 76%, and 75% respectively) among homozygous carriers with baseline IP-10 below 150 pg/mL. In multivariate analyses of genotype 1-infected patients, baseline IP-10 and C genotype at rs12979860 independently predicted the first phase viral decline and RVR, which in turn independently predicted SVR. Conclusions: Concomitant assessment of pretreatment IP-10 and IL28B-related SNPs augments the prediction of the first phase decline in HCV RNA, RVR, and final therapeutic outcome

Core mutations, IL28B polymorphisms and response to peginterferon/ribavirin treatment in Swedish patients with hepatitis C virus genotype 1 infection

<p>Abstract</p> <p>Background</p> <p>Patients infected with hepatitis C virus (HCV) genotype 1 respond poorly to standard treatment with 50% or less achieving sustained virologic response. Predicting outcome is essential and could help avoid unnecessary treatment and reduce health cost. Recently, an association of amino acid substitutions in the core region and treatment outcome was observed in Japanese patients. In the present study, the impact of these mutations on response kinetics and treatment outcome was explored in Caucasian patients.</p> <p>Methods</p> <p>The core region of HCV pre-treatment samples obtained from 50 patients treated with peginterferon/ribavirin in a previous Swedish clinical trial with genotype 1 infection were sequenced. The alleles at rs12979860, a single nucleotide polymorphism (SNP), were assessed in order to identify any co-association with this strong response predictor.</p> <p>Results</p> <p>No association between treatment response and substitutions of core residue 91 was found. In contrast, substitutions of core residue 70 were observed in 6/21 (29%) non-responders, but only in one of 29 responders (p = 0.03), and were more common in subgenotype 1b (R70Q in 6 of 13 strains) than in 1a (R70P in 1 of 37 strains, p = 0.004). The rs12979860 SNP upstream of the IL28B gene was overall the strongest response predictor (p = 0.0001). Core 70 substitutions were associated with poorer response kinetics in patients carrying the CT genotype at rs12979860.</p> <p>Conclusions</p> <p>The results indicate that substitutions of core residue 70 are related to treatment response in Caucasian patients with HCV-1b infection, but are of less importance than IL28B polymorphism.</p

Health-related quality of life after myocardial infarction is associated with level of left ventricular ejection fraction

<p>Abstract</p> <p>Background</p> <p>The objective was to explore the relationship between left ventricular ejection fraction (LVEF) assessed during hospitalization for acute myocardial infarction (MI) and later health-related quality of life (HRQoL).</p> <p>Methods</p> <p>We used multivariable linear regression to assess the relationship between LVEF and HRQoL in 256 MI patients who responded to the Kansas City Cardiomyopathy Questionnaire (KCCQ), the EQ-5D Index, and the EuroQol Visual Analogue Scale (EQ-VAS) 2.5 years after the index MI.</p> <p>Results</p> <p>167 patients had normal LVEF (>50%), 56 intermediate (40%–50%), and 33 reduced (<40%). The mean (SD) KCCQ clinical summary scores were 85 (18), 75 (22), and 68 (21) (<it>p </it><0.001) in the three groups, respectively. The corresponding EQ-5D Index scores were 0.83 (0.18), 0.72 (0.27), and 0.76 (0.14) (<it>p </it>= 0.005) and EQ-VAS scores were 72 (18), 65 (21), and 57 (20) (<it>p </it>= 0.001). In multivariable linear regression analysis age ≥ 70 years, known chronic obstructive pulmonary disease (COPD), subsequent MI, intermediate LVEF, and reduced LVEF were independent determinants for reduced KCCQ clinical summary score. Female sex, medication for angina pectoris at discharge, and intermediate LVEF were independent determinants for reduced EQ-5D Index score. Age ≥ 70 years, COPD, and reduced LVEF were associated with reduced EQ-VAS score.</p> <p>Conclusion</p> <p>LVEF measured during hospitalization for MI was a determinant for HRQoL 2.5 years later.</p

Distinct regulation of c-myb gene expression by HoxA9, Meis1 and Pbx proteins in normal hematopoietic progenitors and transformed myeloid cells

The proto-oncogenic protein c-Myb is an essential regulator of hematopoiesis and is frequently deregulated in hematological diseases such as lymphoma and leukemia. To gain insight into the mechanisms underlying the aberrant expression of c-Myb in myeloid leukemia, we analyzed and compared c-myb gene transcriptional regulation using two cell lines modeling normal hematopoietic progenitor cells (HPCs) and transformed myelomonocytic blasts. We report that the transcription factors HoxA9, Meis1, Pbx1 and Pbx2 bind in vivo to the c-myb locus and maintain its expression through different mechanisms in HPCs and leukemic cells. Our analysis also points to a critical role for Pbx2 in deregulating c-myb expression in murine myeloid cells cotransformed by the cooperative activity of HoxA9 and Meis1. This effect is associated with an intronic positioning of epigenetic marks and RNA polymerase II binding in the orthologous region of a previously described alternative promoter for c-myb. Taken together, our results could provide a first hint to explain the abnormal expression of c-myb in leukemic cells

The effect of acceptance and commitment therapy on insomnia and sleep quality: A systematic review

Background Acceptance and Commitment Therapy (ACT), as a type of behavioral therapy, attempts to respond to changes in people’s performance and their relationship to events. ACT can affect sleep quality by providing techniques to enhance the flexibility of patients’ thoughts, yet maintaining mindfullness. Therefore, for the first time, a systematic review on the effects of ACT on sleep quality has been conducted. Methods This systematic review was performed to determine the effect of ACT on insomnia and sleep quality. To collect articles, the PubMed, Web of Science (WOS), Cochrane library, Embase, Scopus, Science Direct, ProQuest, Mag Iran, Irandoc, and Google Scholar databases were searched, without a lower time-limit, and until April 2020. Results Related articles were derived from 9 research repositories, with no lower time-limit and until April 2020. After assessing 1409 collected studies, 278 repetitive studies were excluded. Moreover, following the primary and secondary evaluations of the remaining articles, 1112 other studies were removed, and finally a total of 19 intervention studies were included in the systematic review process. Within the remaining articles, a sample of 1577 people had been assessed for insomnia and sleep quality. Conclusion The results of this study indicate that ACT has a significant effect on primary and comorbid insomnia and sleep quality, and therefore, it can be used as an appropriate treatment method to control and improve insomnia

Nurse-patient interaction and communication: a systematic literature review

Aim: The purpose of this review is to describe the use and definitions of the concepts of nurse-patient interaction and nurse-patient communication in nursing literature. Furthermore, empirical findings of nurse-patient communication research will be presented, and applied theories will be shown. Method: An integrative literature search was executed. The total number of relevant citations found was 97. The search results were reviewed, and key points were extracted in a standardized form. Extracts were then qualitatively summarized according to relevant aspects and categories for the review. Results: The relation of interaction and communication is not clearly defined in nursing literature. Often the terms are used interchangeably or synonymously, and a clear theoretical definition is avoided or rather implicit. Symbolic interactionism and classic sender-receiver models were by far the most referred to models. Compared to the use of theories of adjacent sciences, the use of original nursing theories related to communication is rather infrequent. The articles that try to clarify the relation of both concepts see communication as a special or subtype of interaction. Conclusion: The included citations all conclude that communication skills can be learned to a certain degree. Involvement of patients and their role in communication often is neglected by authors. Considering the mutual nature of communication, patients’ share in conversation should be taken more into consideration than it has been until now. Nursing science has to integrate its own theories of nursing care with theories of communication and interaction from other scientific disciplines like sociology