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- ArticleSingh BM, Bohara N, Gautam K, Basnet M, Kc S, Kc B, Raut A, Phudong A, Gautam J.Cureus. 2021 Sep;13(9):e18221.Transthyretin amyloid cardiomyopathy disease burden is increasing daily due to advancements in diagnostic and imaging modalities in the modern world. Tafamidis is one of many therapeutic options. The main objective of this review is to study the role of Tafamidis in slowing the progression of transthyretin cardiomyopathy (TTR-CM) by analyzing randomized controlled trials (RCTs) and non-RCTs of Tafamidis. We searched for published papers of Tafamidis in the English language in electronic databases like Google Scholar, PubMed, Cochrane Library, and PubMed Central. We imported the resulting articles from our search to Mendeley software. Four reviewers removed the duplicates and performed title and abstract screening of the articles. The same reviewers obtained the full-text of relevant articles and did full-text screening based on eligibility criteria. Finally, five reviewers performed a quality assessment of RCTs using the Cochrane risk of bias assessment and of non-RCTs by a checklist prepared by Downs and Black. Any disagreements about any process were resolved by a discussion with other authors. One RCT and five non-RCTs of Tafamidis were included in this systematic review. From the non-RCTs, stability was observed in different parameters like echocardiographic findings, cardiac biomarkers, and ECG in patients with transthyretin cardiomyopathy during the study duration with Tafamidis. ATTR-ACT (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial) trial demonstrated reduction of cardiovascular events and all-cause mortality in the Tafamidis group in comparison to placebo. In both RCT and non-RCTs, Tafamidis was established as a safe and tolerable drug for patients with TTR-CM. Our study proved the role of Tafamidis in reducing cardiovascular events, all-cause mortality, and the progression of cardiac disease in TTR-CM patients. In addition to five non-RCTs, current evidence is based on the findings of only one RCT of Tafamidis. Hence, evidence from additional RCTs is required to strongly support the stability of parameters like echocardiographic findings, cardiac biomarkers, and ECG with Tafamidis use.
- ArticleHardeland R.Int J Mol Sci. 2014 Oct 10;15(10):18221-52.Melatonin is a highly pleiotropic regulator molecule, which influences numerous functions in almost every organ and, thus, up- or down-regulates many genes, frequently in a circadian manner. Our understanding of the mechanisms controlling gene expression is actually now expanding to a previously unforeseen extent. In addition to classic actions of transcription factors, gene expression is induced, suppressed or modulated by a number of RNAs and proteins, such as miRNAs, lncRNAs, piRNAs, antisense transcripts, deadenylases, DNA methyltransferases, histone methylation complexes, histone demethylases, histone acetyltransferases and histone deacetylases. Direct or indirect evidence for involvement of melatonin in this network of players has originated in different fields, including studies on central and peripheral circadian oscillators, shift work, cancer, inflammation, oxidative stress, aging, energy expenditure/obesity, diabetes type 2, neuropsychiatric disorders, and neurogenesis. Some of the novel modulators have also been shown to participate in the control of melatonin biosynthesis and melatonin receptor expression. Future work will need to augment the body of evidence on direct epigenetic actions of melatonin and to systematically investigate its role within the network of oscillating epigenetic factors. Moreover, it will be necessary to discriminate between effects observed under conditions of well-operating and deregulated circadian clocks, and to explore the possibilities of correcting epigenetic malprogramming by melatonin.
- ArticleVendrell E, Morales C, Risques RA, Capellà G, Peinado MA.Cancer Lett. 2005 Apr 18;221(1):1-9.Colorectal cancer progression is characterized by the sequential acquisition of multiple genetic aberrations. Insights into the biology of cancer cell and the development of novel methodologies have open a new frontier in the search of independent molecular factors to better predict outcome. Besides the generation of a large list of candidate markers, their applicability in routine clinical settings has been hindered by the heterogeneity of the disease. The analysis of cumulated genetic damage offers a more comprehensive measure of the cancer cell's genomic disruption and appears as a gauge of malignant potential. The prognostic application of different determinants of genomic damage is reviewed.
- ArticleWright SP, Hayden J, Lynd JA, Walker-Finch K, Willett J, Ucer C, Speechley SD.Br Dent J. 2016 Nov 18;221(10):615-622.Objectives The aim of this paper is to identify the factors that affect the complexity of implant restoration and to explore the indices that help us to assess it. With this knowledge the growing number of clinicians restoring dental implants will have a better understanding of the available guidance and evidence base, and the differing levels of competence required.Study design A literature review was conducted. The selection of publications reporting on complexity was based on predetermined criteria and was agreed upon by the authors. After title and abstract screening 17 articles were reviewed. The articles that were utilised to form the ITI SAC tool and Cologne Risk Assessment we also included.Assessing complexity Two key guides are available: International Team for Implantology's Straight-forward Advanced Complex tool and the Cologne ABC risk score. While these guides help identify treatment complexity they do not provide a strong enough evidence base from which to solely base clinical decisions. The key patient factors are expectation, communication, the oral environment, aesthetic outcome, occlusion, soft tissue profile and the intra-arch distance, whereas the key technical factors are impression taking, type of retention, loading protocol and the need for provisional restorations. Human factors also have a significant effect on complexity, specifically, the experience and training of the clinician, team communication and the work environment.Conclusions There are many interconnecting factors that affect the complexity of dental implant restoration. Furthermore the two widely used indices for the assessment of complexity have been investigated, and although these offer a good guideline as to the level of complexity, there is a lack evidence to support their use. The development of evidence-based treatment and protocols is necessary to develop the current indices further, and these need to be expanded to include other critical areas, such as human factors. A practical guide to aid practitioners in reducing complexity has been proposed.
- ArticleSalgado-Peralvo AO, Arriba-Fuente L, Mateos-Moreno MV, Salgado-García A.Br Dent J. 2016 Nov 18;221(10):645-649.Introduction The complications associated with dental implants are numerous, most of them of an inflammatory nature; nevertheless, some isolated cases of oral squamous cell carcinoma (OSCC) have been found in the vicinity of the implants. The objective of the present article is to know whether there is an association between dental implants and the development of OSCC.Method and materials A search was carried out in Medline, Tripdatabase and Cochrane with the keywords 'dental implants' AND 'squamous cell carcinoma', and 'dental implant complications' AND 'squamous cell carcinoma.' The criteria for inclusion were articles published in English that dealt with the possible carcinogenic effects of implants and the possible malign transformation of oral lesions after the insertion of the implants. For the analysis, cases were used in which an OSCC had appeared in the peri-implantary mucosa.Results After an initial search, 269 articles were selected, of which 197 were excluded as not being directly related to the subject. Finally, 45 articles were selected, with 23 of them being used in the analysis. In these, 46 cases of OSCC in the vicinity of implants were discussed.Discussion Chronic inflammation in itself can lead to a malign transformation of the oral tissue, while in other cases it is caused and modulated by carcinogens, genetic factors or inherent factors in the patient, or by the dental implants.Conclusions It is not possible to establish a cause-effect relation between the implants and the development of OSCC. Its presence can be confused with peri-implantitis, so that in the cases where it appears suddenly, does not respond to conventional treatment and/or there is anaesthesia or paresthesia, it is advisable to do a biopsy. It is important to make an adequate selection of the patient and reduce or eliminate the risk factors. The findings of the present review are based on case study level of evidence, so meta-analysis is needed to further draw from these results.