57 research outputs found
A computational approach to investigate TDP-43 C-terminal fragments aggregation in Amyotrophic Lateral Sclerosis
Many of the molecular mechanisms underlying the pathological aggregation of
proteins observed in neurodegenerative diseases are still not fully understood.
Among the diseases associated with protein aggregates, for example, Amyotrophic
Lateral Sclerosis (ALS) is of relevant importance. Although understanding the
processes that cause the disease is still an open challenge, its relationship
with protein aggregation is widely known. In particular, human TDP-43, an
RNA/DNA binding protein, is a major component of pathological cytoplasmic
inclusions described in ALS patients. The deposition of the phosphorylated
full-length TDP-43 in spinal cord cells has been widely studied, and it has
been shown that the brain cortex presents an accumulation of phosphorylated
C-terminal fragments (CTFs). Even if it is debated whether CTFs represent a
primary cause of ALS, they are a hallmark of TDP-43 related neurodegeneration
in the brain. Here, we investigate the CTFs aggregation process, providing a
possible computational model of interaction based on the evaluation of shape
complementarity at the interfaces. To this end, extensive Molecular Dynamics
(MD) simulations were conducted for different types of fragments with the aim
of exploring the equilibrium configurations. Adopting a newly developed
approach based on Zernike polynomials, for finding complementary regions of the
molecular surface, we sampled a large set of exposed portions of the molecular
surface of CTFs structures as obtained from MD simulations. The analysis
proposes a set of possible associations between the CTFs, which could drive the
aggregation process of the CTFs.Comment: 9 pages, 4 figures, 1 tabl
Erratum to nodal management and upstaging of disease. Initial results from the Italian VATS Lobectomy Registry
[This corrects the article DOI: 10.21037/jtd.2017.06.12.]
Uniparental markers of contemporary Italian population reveals details on its pre-Roman heritage.
BACKGROUND: According to archaeological records and historical documentation, Italy has been a melting point for populations of different geographical and ethnic matrices. Although Italy has been a favorite subject for numerous population genetic studies, genetic patterns have never been analyzed comprehensively, including uniparental and autosomal markers throughout the country.
METHODS/PRINCIPAL FINDINGS: A total of 583 individuals were sampled from across the Italian Peninsula, from ten distant (if homogeneous by language) ethnic communities--and from two linguistic isolates (Ladins, Grecani Salentini). All samples were first typed for the mitochondrial DNA (mtDNA) control region and selected coding region SNPs (mtSNPs). This data was pooled for analysis with 3,778 mtDNA control-region profiles collected from the literature. Secondly, a set of Y-chromosome SNPs and STRs were also analyzed in 479 individuals together with a panel of autosomal ancestry informative markers (AIMs) from 441 samples. The resulting genetic record reveals clines of genetic frequencies laid according to the latitude slant along continental Italy--probably generated by demographical events dating back to the Neolithic. The Ladins showed distinctive, if more recent structure. The Neolithic contribution was estimated for the Y-chromosome as 14.5% and for mtDNA as 10.5%. Y-chromosome data showed larger differentiation between North, Center and South than mtDNA. AIMs detected a minor sub-Saharan component; this is however higher than for other European non-Mediterranean populations. The same signal of sub-Saharan heritage was also evident in uniparental markers.
CONCLUSIONS/SIGNIFICANCE: Italy shows patterns of molecular variation mirroring other European countries, although some heterogeneity exists based on different analysis and molecular markers. From North to South, Italy shows clinal patterns that were most likely modulated during Neolithic times
Molecular characterization and clinical relevance of metabolic expression subtypes in human cancers.
Metabolic reprogramming provides critical information for clinical oncology. Using molecular data of 9,125 patient samples from The Cancer Genome Atlas, we identified tumor subtypes in 33 cancer types based on mRNA expression patterns of seven major metabolic processes and assessed their clinical relevance. Our metabolic expression subtypes correlated extensively with clinical outcome: subtypes with upregulated carbohydrate, nucleotide, and vitamin/cofactor metabolism most consistently correlated with worse prognosis, whereas subtypes with upregulated lipid metabolism showed the opposite. Metabolic subtypes correlated with diverse somatic drivers but exhibited effects convergent on cancer hallmark pathways and were modulated by highly recurrent master regulators across cancer types. As a proof-of-concept example, we demonstrated that knockdown of SNAI1 or RUNX1—master regulators of carbohydrate metabolic subtypes-modulates metabolic activity and drug sensitivity. Our study provides a system-level view of metabolic heterogeneity within and across cancer types and identifies pathway cross-talk, suggesting related prognostic, therapeutic, and predictive utility
VATS Biportal Left Pneumonectomy
Pneumonectomy is defined as the removal of the entire lung. This surgical procedure can be performed intrapericardially or extrapericardially and is associated with the radical dissection of the mediastinal lymph node without the resection of the mediastinal chest wall or the diaphragm. Pneumonectomy remains the main surgical choice for managing locally advanced lung cancer that cannot be treated using other anatomic lung resections like lobectomy or parenchyma-sparing procedures such as sleeve resection. The first successful pneumonectomy for cancer was performed by Evarts Graham in 1933 (1). In recent years, pneumonectomy has been performed for 10% of major lung resections. Despite improvements in surgical techniques and perioperative medical care, pneumonectomy is often associated with high perioperative morbidity and mortality (2–5).
The video-assisted thoracoscopic surgery (VATS) approach used to perform lobectomy is widely accepted as a superior alternative to open thoracotomy. This is due to the following benefits: less postoperative pain, lower surgical morbidity, fewer complications, shorter hospital stays, and lower costs (6, 7). Video-assisted thoracoscopic pneumonectomy was first described by Walker in 1994 (8). After that, few reports of thoracoscopic pneumonectomy were published because the VATS approach is associated with technical difficulties (9–11). The purpose of this video is to show the authors’ experience performing a left pneumonectomy using the biportal VATS approach
VATS mediastinal lymph node dissection. Surgical technique and literature review
Objective: With this review we have aimed to present our video-assisted thoracoscopic surgery mediastinal lymph node dissection (VATS MLND) technique and to discuss about its accuracy.Background: VATS resections (lobectomy) have proved to reach the same oncologic outcomes than thoracotomy ones for stage I non-small cell lung cancer. It is also shown that VATS MLND is not inferior to open thoracotomy in terms of accuracy of mediastinal lymph node dissection.Methods: From May 2012 to December 2020, 525 patients were operated of VATS lobectomy with a multiportal approach for NSCLC (468 stage I and 57 stage II-IV) at a high volume Italian Thoracic Surgery Unit: 42 procedures with a 4-port approach, 56 procedures with a 3-ports approach and 427 with a 2-port approach. The main post-operative complications are reported. We described the VATS MLND technique separately as right and left MLND to point out the technical peculiarities of each node station starting with the anatomy. The accuracy of the procedure presented is analyzed in terms of number of lymph node retrieved and upstaging rate comparing our data with that of the most authoritative literature on this topic. We also investigated for the presence of predictors of post-operative complications.Conclusions: We should learn further to became more skilled at performing an adequate VATS lymph node dissection. According to the data presented we can conclude that VATS MLND is a safe and accurate procedure
Tips and tricks in video-assisted thoracoscopic surgery lobectomy
In 2012, open procedures represented 63% of the total number of lobectomies performed in our unit; in 2015, video-assisted thoracoscopic surgery (VATS) lobectomy numbers increased up to 66% of the total number of lobectomies performed. When carrying out the procedures, we followed the guidelines presented by the International VATS Lobectomy Consensus Group regarding indications, contraindications, preoperative investigations and conversions. In view of 280 VATS major lung resections from May 2012 to May 2016, we describe some tips and tricks that can be useful in this surgical technique, from general principles to single operative procedures
Pros-cons debate about the role and evolution of biportal video-assisted thoracoscopic surgery. Luigi Gaetano Andriolo, Camillo Lopez, Dario Gregori, Giovanna Imbriglio, Daniele Bottigliengo, Corrado Surrente, Valentina Larocca, Gaetano Di Rienzo.
Thoracoscopic surgical techniques have numerous advantages compared to open techniques such as decreasing hospital stay, analgesic requirements and postoperative pain. Since the first video-assisted thoracoscopic surgery (VATS) lobectomy performed 20 years ago this procedure, associated with mediastinal lymph node dissection, has been widely accepted as a standard surgical treatment for early stage non-small cell lung cancer. Traditionally the videoscopic approach is based on the three- or four-port approach but more than 50% of the patients developed post-operative chest wall paraesthesia due to nerve injury. In order to avoid this postoperative complication traditional VATS approach has been modified by using few and smaller working ports developing the so called two-portal VATS. The purpose of this study is to establish the advantages of biportal VATS reviewing a series of 400 consecutive cases of VATS lobectomy performed from May 2012 to December 2017, using progressively less ports (4-3-2 ports), at our Institution. There were 42 patients in four-port, 56 patients in three-port and 302 patients in two-port group. A propensity-score analysis showed that, as compared with two- and three-port group, patients in the four-port group had increased duration of chest tube (respectively difference and 95% CI are 1.493, 0.965; 2.053 and 1.246, 0.472; 2.002), increased postoperative length of stay (respectively difference and 95% CI are 2.564, 1.336; 3.952 and 2.205, 0.672; 3.740), increased postoperative pain only in comparison with two-ports (difference and 95% CI in VAS score 1.482, 0.909; 2.055). There were no significant differences in terms of demographic characteristics, histology, type of intervention, number of complications, operative time, number of lymph nodes retrieved and pStage between the three groups
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