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Cells Jan 2021Corticobasal syndrome (CBS) is an atypical parkinsonian presentation characterized by heterogeneous clinical features and different underlying neuropathology. Most CBS...
Corticobasal syndrome (CBS) is an atypical parkinsonian presentation characterized by heterogeneous clinical features and different underlying neuropathology. Most CBS cases are sporadic; nevertheless, reports of families and isolated individuals with genetically determined CBS have been reported. In this systematic review, we analyze the demographical, clinical, radiological, and anatomopathological features of genetically confirmed cases of CBS. A systematic search was performed using the PubMed, EMBASE, and Cochrane Library databases, included all publications in English from 1 January 1999 through 1 August 2020. We found forty publications with fifty-eight eligible cases. A second search for publications dealing with genetic risk factors for CBS led to the review of eight additional articles. was the most common gene involved in CBS, representing 28 out of 58 cases, followed by , and . A set of symptoms was shown to be significantly more common in -CBS patients, including visuospatial impairment, behavioral changes, aphasia, and language alterations. In addition, specific demographical, clinical, biochemical, and radiological features may suggest mutations in other genes. We suggest a diagnostic algorithm to help in identifying potential genetic cases of CBS in order to improve the diagnostic accuracy and to better understand the still poorly defined underlying pathogenetic process.
Topics: Age of Onset; Aged; Aphasia; C9orf72 Protein; Female; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Language Disorders; Male; Mental Disorders; Middle Aged; Mutation; Neurodegenerative Diseases; Parkinsonian Disorders; Prion Proteins; Progranulins; Syndrome; Treatment Outcome; Vision Disorders; tau Proteins
PubMed: 33467748
DOI: 10.3390/cells10010171 -
Environment International Jan 2021Several reviews of synergisms and antagonisms in chemical mixtures have concluded that synergisms are relatively rare. However, these reviews focused on mixtures... (Review)
Review
BACKGROUND
Several reviews of synergisms and antagonisms in chemical mixtures have concluded that synergisms are relatively rare. However, these reviews focused on mixtures composed of specific groups of chemicals, such as pesticides or metals and on toxicity endpoints mostly relevant to ecotoxicology. Doubts remain whether these findings can be generalised. A systematic review not restricted to specific chemical mixtures and including mammalian and human toxicity endpoints is missing.
OBJECTIVES
We conducted a systematic review and quantitative reappraisal of 10 years' of experimental mixture studies to investigate the frequency and reliability of evaluations of mixture effects as synergistic or antagonistic. Unlike previous reviews, we did not limit our efforts to certain groups of chemicals or specific toxicity outcomes and covered mixture studies relevant to ecotoxicology and human/mammalian toxicology published between 2007 and 2017.
DATA SOURCES, ELIGIBILITY CRITERIA
We undertook searches for peer-reviewed articles in PubMed, Web of Science, Scopus, GreenFile, ScienceDirect and Toxline and included studies of controlled exposures of environmental chemical pollutants, defined as unintentional exposures leading to unintended effects. Studies with viruses, prions or therapeutic agents were excluded, as were records with missing details on chemicals' identities, toxicities, doses, or concentrations.
STUDY APPRAISAL AND SYNTHESIS METHODS
To examine the internal validity of studies we developed a risk-of-bias tool tailored to mixture toxicology. For a subset of 388 entries that claimed synergisms or antagonisms, we conducted a quantitative reappraisal of authors' evaluations by deriving ratios of predicted and observed effective mixture doses (concentrations).
RESULTS
Our searches produced an inventory of 1220 mixture experiments which we subjected to subgroup analyses. Approximately two thirds of studies did not incorporate more than 2 components. Most experiments relied on low-cost assays with readily quantifiable endpoints. Important toxicity outcomes of relevance for human risk assessment (e.g. carcinogenicity, genotoxicity, reproductive toxicity, immunotoxicity, neurotoxicity) were rarely addressed. The proportion of studies that declared additivity, synergism or antagonisms was approximately equal (one quarter each); the remaining quarter arrived at different evaluations. About half of the 1220 entries were rated as "definitely" or "probably" low risk of bias. Strikingly, relatively few claims of synergistic or antagonistic effects stood up to scrutiny in terms of deviations from expected additivity that exceed the boundaries of acceptable between-study variability. In most cases, the observed mixture doses were not more than two-fold higher or lower than the predicted additive doses. Twenty percent of the entries (N = 78) reported synergisms in excess of that degree of deviation. Our efforts of pinpointing specific factors that predispose to synergistic interactions confirmed previous concerns about the synergistic potential of combinations of triazine, azole and pyrethroid pesticides at environmentally relevant doses. New evidence of synergisms with endocrine disrupting chemicals and metal compounds such as chromium (VI) and nickel in combination with cadmium has emerged.
CONCLUSIONS, LIMITATIONS AND IMPLICATIONS
These specific cases of synergisms apart, our results confirm the utility of default application of the dose (concentration) addition concept for predictive assessments of simultaneous exposures to multiple chemicals. However, this strategy must be complemented by an awareness of the synergistic potential of specific classes of chemicals. Our conclusions only apply to the chemical space captured in published mixture studies which is biased towards relatively well-researched chemicals.
SYSTEMATIC REVIEW REGISTRATION NUMBER
The final protocol was published on the open-access repository Zenodo and attributed the following digital object identifier, doi: https://doi.org//10.5281/zenodo.1319759 (https://zenodo.org/record/1319759#.XXIzdy7dsqM).
Topics: Animals; Drug Interactions; Endocrine Disruptors; Environmental Pollutants; Humans; Pesticides; Reproducibility of Results
PubMed: 33120228
DOI: 10.1016/j.envint.2020.106206 -
Journal of Translational Medicine Sep 2020Foetal bovine serum (FBS), is the most commonly used culture medium additive for in vitro cultures, despite its undefined composition, its potential immunogenicity and...
BACKGROUND
Foetal bovine serum (FBS), is the most commonly used culture medium additive for in vitro cultures, despite its undefined composition, its potential immunogenicity and possible prion/zoonotic transmission. For these reasons, significant efforts have been targeted at finding a substitute, such as serum free-media or human platelet-lysates (hPL). Our aim is to critically appraise the state-of-art for hPL in the published literature, comparing its impact with FBS.
MATERIALS AND METHODS
In June 2019 a systematic search of the entire Web of Science, Medline and PubMed database was performed with the following search terms: (mesenchymal stem cells) AND (fetal bovine serum OR fetal bovine calf) AND (human platelet lysate). Excluded from this search were review articles that were published before 2005, manuscripts in which mesenchymal stem cells (MSCs) were not from human sources, and when the FBS controls were missing.
RESULTS
Based on our search algorithm, 56 papers were selected. A review of these papers indicated that hMSCs cultured with hPL showed a spindle-shaped elongated morphology, had higher proliferation indexes, similar cluster of differentiation (CD) markers and no significant variation in differentiation lineage (osteocyte, adipocyte, and chondrocyte) compared to those cultured with FBS. Main sources of primary hMSCs were either fat tissue or bone marrow; in a few studies cells isolated from alternative sources showed no relevant difference in their response.
CONCLUSION
Despite the difference in medium choice and a lack of standardization of hPL manufacturing, the majority of publications support that hPL was at least as effective as FBS in promoting adhesion, survival and proliferation of hMSCs. We conclude that hPL should be considered a viable alternative to FBS in hMSCs culture-especially with a view for their clinical use.
Topics: Animals; Blood Platelets; Cattle; Cell Culture Techniques; Cell Differentiation; Cell Proliferation; Cells, Cultured; Culture Media; Humans; Mesenchymal Stem Cells; Serum; Serum Albumin, Bovine
PubMed: 32933520
DOI: 10.1186/s12967-020-02489-4 -
Endoscopic treatment of large symptomatic colon lipomas: A systematic review of efficacy and safety.United European Gastroenterology Journal Dec 2020Various techniques have been described for endoscopic resection of large symptomatic colon lipomas. Lipoma unroofing might provide a safer, more time efficient and... (Comparative Study)
Comparative Study
BACKGROUND
Various techniques have been described for endoscopic resection of large symptomatic colon lipomas. Lipoma unroofing might provide a safer, more time efficient and easier technique compared to dissection-based techniques, endoscopic mucosal resection (EMR) or loop-assisted resection. The aim of this systematic review was to compare efficacy and safety (endoscopic resolution rates, clinical remission rates and adverse events) of lipoma unroofing with respect to dissection-based techniques, EMR or loop-assisted resection.
METHODS
As most outcomes were binary in nature and several outcomes did not occur in some studies, routine calculation of standard errors in outcome probability was not possible. Therefore, original patient data were extracted, after which efficacy and safety were compared.
RESULTS
Twenty four studies met the selection criteria, which encompassed 77 lesions (46.8% female, mean age 63 years (interquartile range (IQR) 53-72 years), mean size 45.4 mm (IQR 30.0-60.0 mm). Ten patients underwent unroofing (13.0%), whereas 7 (9.1%), 31 (40.3%) and 29 patients (37.7%) underwent dissection-based techniques, EMR and loop-assisted-snare resection, respectively. Endoscopic resolution rates were 60%, 100% ( = 0.103), 93.6% ( = 0.024) and 93.1% ( = 0.028). Clinical remission rates were identical in all four groups (100%). Amongst patients who underwent EMR and loop-assisted techniques, adverse events were identified in 12.9% ( = 0.556) and 13.8% ( = 0.556), respectively, compared to none in the unroofing and dissection-based resection group.
CONCLUSIONS
In patients with large colon lipomas, endoscopic treatment by unroofing, dissection-based resection, EMR and loop-assisted resection provided similar clinical remission rates. Amongst patients undergoing EMR and loop-assisted resection, increased endoscopic resolution rates were seen at the expense of more adverse events, although the latter did not reach statistical significance. Until more reliable comparative data are available, the most optimal resection technique should rely on local expertise and patient profile.
Topics: Colon; Colonic Neoplasms; Colonoscopy; Endoscopic Mucosal Resection; Humans; Intestinal Mucosa; Lipoma; Observational Studies as Topic; Postoperative Complications; Treatment Outcome; Tumor Burden
PubMed: 32746773
DOI: 10.1177/2050640620948661 -
International Journal of Molecular... Mar 2020Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases (NDs), presenting a broad range of symptoms from motor dysfunctions...
Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases (NDs), presenting a broad range of symptoms from motor dysfunctions to psychobehavioral manifestations. A common clinical course is the proteinopathy-induced neural dysfunction leading to anatomically corresponding neuropathies. However, current diagnostic criteria based on pathology and symptomatology are of little value for the sake of disease prevention and drug development. Overviewing the pathomechanism of NDs, this review incorporates systematic reviews on inflammatory cytokines and tryptophan metabolites kynurenines (KYNs) of human samples, to present an inferential method to explore potential links behind NDs. The results revealed increases of pro-inflammatory cytokines and neurotoxic KYNs in NDs, increases of anti-inflammatory cytokines in AD, PD, Huntington's disease (HD), Creutzfeldt-Jakob disease, and human immunodeficiency virus (HIV)-associated neurocognitive disorders, and decreases of neuromodulatory KYNs in AD, PD, and HD. The results reinforced a strong link between inflammation and neurotoxic KYNs, confirmed activation of adaptive immune response, and suggested a possible role in the decrease of neuromodulatory KYNs, all of which may contribute to the development of chronic low grade inflammation. Commonalities of multifactorial NDs were discussed to present a current limit of diagnostic criteria, a need for preclinical biomarkers, and an approach to search the initiation factors of NDs.
Topics: Alzheimer Disease; Anti-Inflammatory Agents; Biomarkers; Cytokines; Humans; Huntington Disease; Inflammation; Kynurenine; Neurodegenerative Diseases; Parkinson Disease; Reactive Oxygen Species; Tryptophan
PubMed: 32244523
DOI: 10.3390/ijms21072431 -
Health Technology Assessment... Feb 2020Creutzfeldt-Jakob disease is a fatal neurological disease caused by abnormal infectious proteins called prions. Prions that are present on surgical instruments cannot be...
BACKGROUND
Creutzfeldt-Jakob disease is a fatal neurological disease caused by abnormal infectious proteins called prions. Prions that are present on surgical instruments cannot be completely deactivated; therefore, patients who are subsequently operated on using these instruments may become infected. This can result in surgically transmitted Creutzfeldt-Jakob disease.
OBJECTIVE
To update literature reviews, consultation with experts and economic modelling published in 2006, and to provide the cost-effectiveness of strategies to reduce the risk of surgically transmitted Creutzfeldt-Jakob disease.
METHODS
Eight systematic reviews were undertaken for clinical parameters. One review of cost-effectiveness was undertaken. Electronic databases including MEDLINE and EMBASE were searched from 2005 to 2017. Expert elicitation sessions were undertaken. An advisory committee, convened by the National Institute for Health and Care Excellence to produce guidance, provided an additional source of information. A mathematical model was updated focusing on brain and posterior eye surgery and neuroendoscopy. The model simulated both patients and instrument sets. Assuming that there were potentially 15 cases of surgically transmitted Creutzfeldt-Jakob disease between 2005 and 2018, approximate Bayesian computation was used to obtain samples from the posterior distribution of the model parameters to generate results. Heuristics were used to improve computational efficiency. The modelling conformed to the National Institute for Health and Care Excellence reference case. The strategies evaluated included neither keeping instruments moist nor prohibiting set migration; ensuring that instruments were kept moist; prohibiting instrument migration between sets; and employing single-use instruments. Threshold analyses were undertaken to establish prices at which single-use sets or completely effective decontamination solutions would be cost-effective.
RESULTS
A total of 169 papers were identified for the clinical review. The evidence from published literature was not deemed sufficiently strong to take precedence over the distributions obtained from expert elicitation. Forty-eight papers were identified in the review of cost-effectiveness. The previous modelling structure was revised to add the possibility of misclassifying surgically transmitted Creutzfeldt-Jakob disease as another neurodegenerative disease, and assuming that all patients were susceptible to infection. Keeping instruments moist was estimated to reduce the risk of surgically transmitted Creutzfeldt-Jakob disease cases and associated costs. Based on probabilistic sensitivity analyses, keeping instruments moist was estimated to on average result in 2.36 (range 0-47) surgically transmitted Creutzfeldt-Jakob disease cases (across England) caused by infection occurring between 2019 and 2023. Prohibiting set migration or employing single-use instruments reduced the estimated risk of surgically transmitted Creutzfeldt-Jakob disease cases further, but at considerable cost. The estimated costs per quality-adjusted life-year gained of these strategies in addition to keeping instruments moist were in excess of £1M. It was estimated that single-use instrument sets (currently £350-500) or completely effective cleaning solutions would need to cost approximately £12 per patient to be cost-effective using a £30,000 per quality-adjusted life-year gained value.
LIMITATIONS
As no direct published evidence to implicate surgery as a cause of Creutzfeldt-Jakob disease has been found since 2005, the estimations of potential cases from elicitation are still speculative. A particular source of uncertainty was in the number of potential surgically transmitted Creutzfeldt-Jakob disease cases that may have occurred between 2005 and 2018.
CONCLUSIONS
Keeping instruments moist is estimated to reduce the risk of surgically transmitted Creutzfeldt-Jakob disease cases and associated costs. Further surgical management strategies can reduce the risks of surgically transmitted Creutzfeldt-Jakob disease but have considerable associated costs.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42017071807.
FUNDING
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 24, No. 11. See the NIHR Journals Library website for further project information.
Topics: Cost-Benefit Analysis; Creutzfeldt-Jakob Syndrome; England; Humans; Models, Economic; Prions; Quality-Adjusted Life Years; Technology Assessment, Biomedical
PubMed: 32122460
DOI: 10.3310/hta24110 -
Tremor and Other Hyperkinetic Movements... 2019Movement disorders are frequent features of prionopathies. However, their prevalence and onset remain poorly described.
BACKGROUND
Movement disorders are frequent features of prionopathies. However, their prevalence and onset remain poorly described.
METHODS
We performed a systematic review of case reports and case series of pathologically- and genetically confirmed prionopathies. Timing of symptom and movement disorder onset were documented. Continuous variables were compared between two groups using the Wilcoxon rank sum test and between multiple groups using Kruskal-Wallis test. Categorical variables were compared using Fisher's exact test.
RESULTS
A total of 324 cases were included in this analysis. Movement disorders were a common feature at the onset of symptoms in most prionopathies. Gait ataxia was present in more than half of cases in all types of prionopathies. The prevalence of limb ataxia (20%) and myoclonus (24%) was lower in Gerstmann-Sträussler-Scheinker disease compared to other prionopathies (p ≤ 0.004). Myoclonus was common but often a later feature in sporadic Creutzfeldt-Jakob disease (2 months before death). Chorea was uncommon but disproportionately prevalent in variant Creutzfeldt-Jakob disease (30% of cases; p < 0.001). In genetic Creutzfeldt-Jakob disease, E200K carriers exhibited gait and limb ataxia more often when compared to other mutation carriers.
DISCUSSION
Movement disorders are differentially present in the course of the various prionopathies. The movement phenomenology and appearance are associated with the type of prion disease and the genotype and likely reflect the underlying pattern of neurodegeneration. Reliance on myoclonus as a diagnostic feature of sporadic Creutzfeldt-Jakob disease may delay its recognition given its relatively late appearance in the disease course.
Topics: Humans; Movement Disorders; Mutation; Myoclonus; Prion Diseases
PubMed: 31871824
DOI: 10.7916/tohm.v0.712 -
Progress in Neurobiology Nov 2019While the root causes for individual neurodegenerative diseases are distinct, many shared pathological features and mechanisms contribute to neurodegeneration across...
While the root causes for individual neurodegenerative diseases are distinct, many shared pathological features and mechanisms contribute to neurodegeneration across diseases. Altered levels of microRNAs, small non-coding RNAs involved in post transcriptional regulation of gene expression, are reported for numerous neurodegenerative diseases. Yet, comparison between diseases to uncover commonly dysregulated microRNAs during neurodegeneration in general is lagging. We performed a systematic review of peer-reviewed publications describing differential microRNA expression in neurodegenerative diseases and related animal models. We compiled the results from studies covering the prevalent neurodegenerative diseases in the literature: Alzheimer's disease, amyotrophic lateral sclerosis, age-related macular degeneration, ataxia, dementia, myotonic dystrophy, epilepsy, glaucoma, Huntington's disease, multiple sclerosis, Parkinson's disease, and prion disorders. MicroRNAs which were dysregulated most often in these diseases and their models included miR-9-5p, miR-21-5p, the miR-29 family, miR-132-3p, miR-124-3p, miR-146a-5p, miR-155-5p, and miR-223-3p. Common pathways targeted by these predominant miRNAs were identified and revealed great functional overlap across diseases. We also identified a strong role for each microRNA in both the neural and immune components of diseases. microRNAs regulate broad networks of genes and identifying microRNAs commonly dysregulated across neurodegenerative diseases could cultivate novel hypotheses related to common molecular mechanisms underlying neurodegeneration.
Topics: Animals; Brain; Disease Models, Animal; Gene Expression Regulation; Humans; MicroRNAs; Neurodegenerative Diseases
PubMed: 31356849
DOI: 10.1016/j.pneurobio.2019.101664 -
Acta Neurologica Belgica Sep 2018Sporadic Creutzfeldt-Jakob disease (sCJD) is a human prion disease that is a relatively common differential diagnosis in dementia patients. Therefore it needs a good... (Review)
Review
A systematic review comparing the diagnostic value of 14-3-3 protein in the cerebrospinal fluid, RT-QuIC and RT-QuIC on nasal brushing in sporadic Creutzfeldt-Jakob disease.
BACKGROUND
Sporadic Creutzfeldt-Jakob disease (sCJD) is a human prion disease that is a relatively common differential diagnosis in dementia patients. Therefore it needs a good diagnostic tool. Brain autopsy is the golden standard for the diagnosis of CJD; however, a less invasive technique is 14-3-3 protein measurement in the cerebrospinal fluid (CSF). In this systematic review, we compared the diagnostic value of the 14-3-3 protein measurement to the newer RT-QuIC test and a variant of RT-QuIC where nasal brushing is used to collect the samples.
METHODS
The search via MeSH terms and quality assessment was carried out by two individual researchers.
RESULTS
In 14-3-3 and RT-QuIC the sensitivity was comparable, respectively, 88% and 86%. Specificity however was higher in RT-QuIC 99.5% compared to 80% in 14-3-3. Nasal brushing showed the best results with a sensitivity of 97% and a specificity of 100%.
CONCLUSION
Nasal brushing, despite being the best diagnostic tool according to the data, needs more study since there has only been a few studies regarding the technique. It is safe to say that due to the high specificity, RT-QuIC is superior to 14-3-3 testing.
Topics: 14-3-3 Proteins; Biomarkers; Brain; Creutzfeldt-Jakob Syndrome; Humans; Sensitivity and Specificity
PubMed: 30097826
DOI: 10.1007/s13760-018-0995-8 -
Journal of Clinical Medicine Research Mar 2018Tonometry has been identified as a common method for measuring the intraocular pressure in patients. The direct contact between the tonometer and the eye may contribute... (Review)
Review
Tonometry has been identified as a common method for measuring the intraocular pressure in patients. The direct contact between the tonometer and the eye may contribute to the risk of cross infection, especially of viral particles, from one patient to another. A systematic review was undertaken to address the likelihood of human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus, and prion diseases transmission through the use of tonometers. Additionally, a comparison of the current tonometer disinfection methods is provided to assist with identifying which technique effectively reduces the risk of disease transmission. An electronic literature search was conducted using the following databases: Web of Science, EMBASE, CINAHL, SCOPUS, Biosis Previews, Cochrane Library, PubMed, and Google Scholar. Dissertation indexes were also searched, and these included: Dissertations and Abstracts, and Dissertations and Abstracts - UK/Ireland. Additionally, the Clinicaltrials.gov trial registry was searched to identify any other relevant literature. Two independent reviewers critically appraised the articles retrieved through the literature search. In total, 11 unique studies were deemed relevant for this systematic review. The available evidence demonstrated that the use of tonometers contributes to the transmission of these infectious diseases . The results also demonstrated variability in determining the most effective tonometer sterilization technique against these infectious diseases . There was limited evidence available regarding the transmission of HIV, hepatitis B, hepatitis C, and prion diseases through the use of tonometers. Additionally, due to the variability regarding the most effective sterilization techniques, it is difficult to identify which sterilization technique is most effective or adequately effective against these infectious diseases. Future research studies regarding infectious disease transmission through tonometry and sterilization techniques should be completed to more adequately inform infectious disease control guidelines.
PubMed: 29416571
DOI: 10.14740/jocmr3294w