scholarly journals A New Tool for the Analysis of the Effect of Intracerebrally Injected Anti-Amyloid-β Compounds

2021 ◽  
pp. 1-14
Author(s):  
Jolanta Upte ◽  
Thomas Brüning ◽  
Luisa Möhle ◽  
Mirjam Brackhan ◽  
Pablo Bascuñana ◽  
...  

Background: A wide range of techniques has been developed over the past decades to characterize amyloid-β (Aβ) pathology in mice. Until now, no method has been established to quantify spatial changes in Aβ plaque deposition due to targeted delivery of substances using ALZET ® pumps. Objective: Development of a methodology to quantify the local distribution of Aβ plaques after intracerebral infusion of compounds. Methods: We have developed a toolbox to quantify Aβ plaques in relation to intracerebral injection channels using Zeiss AxioVision ® and Microsoft Excel ® software. For the proof of concept, intracerebral stereotactic surgery was performed in 50-day-old APP-transgenic mice injected with PBS. At the age of 100 days, brains were collected for immunhistological analysis. Results: The toolbox can be used to analyze and evaluate Aβ plaques (number, size, and coverage) in specific brain areas based on their location relative to the point of the injection or the injection channel. The tool provides classification of Aβ plaques in pre-defined distance groups using two different approaches. Conclusion: This new analytic toolbox facilitates the analysis of long-term continuous intracerebral experimental compound infusions using ALZET ® pumps. This method generates reliable data for Aβ deposition characterization in relation to the distribution of experimental compounds.

2019 ◽  
Vol 20 (3) ◽  
pp. 251-264 ◽  
Author(s):  
Yinlu Feng ◽  
Zifei Yin ◽  
Daniel Zhang ◽  
Arun Srivastava ◽  
Chen Ling

The success of gene and cell therapy in clinic during the past two decades as well as our expanding ability to manipulate these biomaterials are leading to new therapeutic options for a wide range of inherited and acquired diseases. Combining conventional therapies with this emerging field is a promising strategy to treat those previously-thought untreatable diseases. Traditional Chinese medicine (TCM) has evolved for thousands of years in China and still plays an important role in human health. As part of the active ingredients of TCM, proteins and peptides have attracted long-term enthusiasm of researchers. More recently, they have been utilized in gene and cell therapy, resulting in promising novel strategies to treat both cancer and non-cancer diseases. This manuscript presents a critical review on this field, accompanied with perspectives on the challenges and new directions for future research in this emerging frontier.


1988 ◽  
Vol 18 (2) ◽  
pp. 365-374 ◽  
Author(s):  
Susan Golombok ◽  
Parimala Moodley ◽  
Malcolm Lader

SynopsisIn view of the very extensive and often prolonged use of benzodiazepines in therapeutic practice, this study was designed to investigate whether or not cognitive ability is impaired in longterm benzodiazepine users, and to determine the nature and extent of any deficit. Fifty patients currently taking benzodiazepines for at least one year, thirty-four who had stopped taking benzodiazepines, and a matched control group of subjects who had never taken benzodiazepines or who had taken benzodiazepines in the past for less than one year were administered a battery of neuropsychological tests designed to measure a wide range of cognitive functions. It was found that patients taking high doses of benzodiazepines for long periods of time perform poorly on tasks involving visual-spatial ability and sustained attention. This is consistent with deficits in posterior cortical cognitive function.


2016 ◽  
Vol 101 (9) ◽  
pp. e2.54-e2
Author(s):  
Jeff Aston ◽  
Keith Wilson ◽  
David Terry

AimTo identify the experiences of patients, parents or carers when a child/young person is prescribed a new long-term medicine.MethodPatients' prescribed a new long-term (>6 weeks) medicine were recruited from a single UK paediatric hospital out-patient pharmacy.A semi-structured questionnaire was administered to participants, via telephone, 6 weeks after the dispensing of their medicine. The questionnaire included the following themes: information requirements, resources used to seek further information, medicine administration issues, new concerns or questions that have arisen, adverse effects, arranging repeat supplies and an assessment of adherence.The results were analysed using Microsoft Excel 2013 and NVivo Version 10.ResultsFifty patients consented and were included in the study. Eighteen (36%) participants had undertaken further research prior to taking/administering their new medicine. 13 (72%) of these used the internet for further information. Participants had further concerns/questions in 18 (36%) cases with 7 (38.9%) contacting the hospital team for further advice. Thirteen (26%) participants experienced difficulty administering/taking the medicine. Sixteen (36%) believed that they had experienced an adverse effect. Eight (16%) participants experienced difficulties when obtaining further supplies. With regard to adherence, 17 (34%) participants had forgotten a dose on at least one occasion and 4 (8%) found it difficult to keep to the medication regimen.ConclusionThis research has demonstrated that paediatric patients, parents and carers experience a wide range of issues during the first few weeks after starting a new medicine. This is in accordance with a recent review of non-adherence in paediatric long-term medical conditions.1 The New Medicines Service (NMS) offered through community pharmacists is designed to support patients' who have recently been prescribed a medicine to manage a long-term condition.2 However, this is not readily available to children/young people or their carers. The main barriers being the targeted conditions included in the service, consent and exclusion of undertaking an NMS consultation with a carer. Further research is required to establish and evaluate a paediatric specific medication review service for children/young people and their parents/carers when a new long-term medicine has been prescribed. This research will support the recent research recommendation of the National Institute of Health and Care Excellence.3


Author(s):  
Yi Ge Zhang ◽  
Mark Pagani ◽  
Zhonghui Liu ◽  
Steven M. Bohaty ◽  
Robert DeConto

The alkenone– p CO 2 methodology has been used to reconstruct the partial pressure of ancient atmospheric carbon dioxide ( p CO 2 ) for the past 45 million years of Earth's history (Middle Eocene to Pleistocene epochs). The present long-term CO 2 record is a composite of data from multiple ocean localities that express a wide range of oceanographic and algal growth conditions that potentially bias CO 2 results. In this study, we present a p CO 2 record spanning the past 40 million years from a single marine locality, Ocean Drilling Program Site 925 located in the western equatorial Atlantic Ocean. The trends and absolute values of our new CO 2 record site are broadly consistent with previously published multi-site alkenone–CO 2 results. However, new p CO 2 estimates for the Middle Miocene are notably higher than published records, with average p CO 2 concentrations in the range of 400–500 ppm. Our results are generally consistent with recent p CO 2 estimates based on boron isotope-pH data and stomatal index records, and suggest that CO 2 levels were highest during a period of global warmth associated with the Middle Miocene Climatic Optimum (17–14 million years ago, Ma), followed by a decline in CO 2 during the Middle Miocene Climate Transition (approx. 14 Ma). Several relationships remain contrary to expectations. For example, benthic foraminiferal δ 18 O records suggest a period of deglaciation and/or high-latitude warming during the latest Oligocene (27–23 Ma) that, based on our results, occurred concurrently with a long-term decrease in CO 2 levels. Additionally, a large positive δ 18 O excursion near the Oligocene–Miocene boundary (the Mi-1 event, approx. 23 Ma), assumed to represent a period of glacial advance and retreat on Antarctica, is difficult to explain by our CO 2 record alone given what is known of Antarctic ice sheet history and the strong hysteresis of the East Antarctic Ice Sheet once it has grown to continental dimensions. We also demonstrate that in the Neogene with low CO 2 levels, algal carbon concentrating mechanisms and spontaneous biocarbonate–CO 2 conversions are likely to play a more important role in algal carbon fixation, which provides a potential bias to the alkenone– p CO 2 method.


Author(s):  
Josh Feiser ◽  
Vijay V. Raghavan ◽  
Teuta Cata

Mobile devices and applications are becoming popular in today’s society. The number of applications available to both the patient and the healthcare provider is changing the way healthcare is being delivered and consumed. The integration of mobile devices into every-day lives is driving the changes in healthcare. While all areas of medicine are being impacted, changes are mostly of chronic care, long term care and any place that causes a need for constant data, monitoring or training. The acceptance of mobile devices by healthcare consumers within wide range of age and socioeconomic circumstances is reason to look at mobile technology as the future of healthcare. While increased use of mobile applications are welcomed by most providers and consumers alike, there is a need to systematize the study of its use. The authors provide a framework for considering mobile applications in healthcare, based on their risk-profile. They accomplish this by first identifying and classifying the mobile healthcare applications.


2012 ◽  
Vol 8 (S287) ◽  
pp. 199-208
Author(s):  
Anita M. S. Richards

AbstractThis review summarises current observations of masers around evolved stars and models for their location and behaviour, followed by some of the many highlights from the past 5 years. Some of these have been the fruition of long-term monitoring, a vital aspect of study of stars which are both periodically variable and prone to rapid outbursts or transition to a new evolutionary stage. Interferometric imaging of masers provide the highest-resolution probes of the stellar wind, but their exponential amplification and variability means that multiple observations are needed to investigate questions such as what drives the wind from the stellar surface; why does it accelerate slowly over many tens of stellar radii; what causes maser variability. VLBI parallaxes have improved our understanding of individual objects and of Galactic populations. Masers from wide range of binary and post-AGB objects are accessible to sensitive modern instruments, including energetic symbiotic systems. Masers have been detected up to THz frequencies withHerscheland ALMA's ability to resolve a wide range of maser and thermal lines will provide accurate constraints on physical conditions including during dust formation.


1969 ◽  
Vol 14 (6) ◽  
pp. 591-600 ◽  
Author(s):  
Conrad J. Schwarz

This paper is based on a review of the English language medical literature over the past 35 years on Indian Hemp, with direct reference being made to the more significant articles published during that time. The paucity of direct experimental observation is noted and the difficulties in experimental studies are highlighted by descriptions of the wide variations in the potency of Indian Hemp derivatives. Specific references are provided for the wide range of observations made in relation to acute and chronic physical and psychological effects, personal characteristics of the users and possible factors in causation. It is concluded that marihuana is a poorly defined intoxicant which varies in potency, deteriorates with time and whose chemical composition is largely unknown at present. There are wide variations in human response and the state of intoxication itself carries with it varying degrees of unpleasant physical and psychological experiences. The association between hashish and, to a lesser extent, marihuana and short-term and long-term complications is discussed in relation to complex variables, of which the drug is but one factor.


Author(s):  
Emily W. B. Russell Southgate

There are many field techniques that take research beyond what can be found in written documents. Clues to the past are hidden in such subtle (and not so subtle) features as topographic modifications, soils, and tree trunks. Field studies search for evidence of conditions and for their resultant effects through a variety of techniques. Features may be evident from a ground survey, located precisely through GPS. Remote imaging, using a variety of techniques from simple aerial photography to lidar, reveal hidden patterns, that may then be studied on the ground. Archeological study relates the patterns found on the ground to human activities, as they have changed over time. Dendroecology interprets records left in tree rings. Some studies look at stands of different ages to study change over time, and long-term studies trace change in individual stands. In these field studies that look at the past, soil characteristics and materials hidden in the soil, such as DNA, stable isotopes and charcoal, can reveal details of past processes and species. These methods are illustrated with examples from a wide range of biomes.


2019 ◽  
Vol 116 (5) ◽  
pp. 1639-1644 ◽  
Author(s):  
Martin Petr ◽  
Svante Pääbo ◽  
Janet Kelso ◽  
Benjamin Vernot

Several studies have suggested that introgressed Neandertal DNA was subjected to negative selection in modern humans. A striking observation in support of this is an apparent monotonic decline in Neandertal ancestry observed in modern humans in Europe over the past 45,000 years. Here, we show that this decline is an artifact likely caused by gene flow between modern human populations, which is not taken into account by statistics previously used to estimate Neandertal ancestry. When we apply a statistic that avoids assumptions about modern human demography by taking advantage of two high-coverage Neandertal genomes, we find no evidence for a change in Neandertal ancestry in Europe over the past 45,000 years. We use whole-genome simulations of selection and introgression to investigate a wide range of model parameters and find that negative selection is not expected to cause a significant long-term decline in genome-wide Neandertal ancestry. Nevertheless, these models recapitulate previously observed signals of selection against Neandertal alleles, in particular the depletion of Neandertal ancestry in conserved genomic regions. Surprisingly, we find that this depletion is strongest in regulatory and conserved noncoding regions and in the most conserved portion of protein-coding sequences.


2020 ◽  
Vol 12 (20) ◽  
pp. 8478
Author(s):  
Soohyon Kim ◽  
Wook Sohn ◽  
Changyong Choi

Confronting the continuing economic sanctions, the flood disaster, and the COVID 19, North Korea is now in a critical phase whether the North Korean economy will shift to a sustainable economy or, as it has done in the past three decades, barely manage to maintain at a survival level. To explore the question, this study investigates North Korea’s economic policy changes by extracting the keywords from the North Korean economic journal Economic Research, which is a representative state published document. We use a text mining approach to overcome limitations, such as the lack of objectivity and accuracy of the classification of topics in manual text analysis for North Korean studies. Contrary to the conventional assumption that the North Korean economic policies are driven by dogmatic Juche (self-reliance) ideology, we find that the strategy of economic policies differs depending on the leader and political and economic circumstances at the time. In particular, since Kim Jong-un assumed office in 2011, the topics have diversified, and now cover a wide range of subjects on capitalism. Nevertheless, without North Korea’s decisive reform measures and international cooperation, it will be hard to observe that the North Korean economy can go beyond ‘muddling-through’ for sustainable development.


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