Physicochemical attack against solid tumors based on the reversal of direction of entropy flow: an attempt to introduce thermodynamics in anticancer therapy

BACKGROUND: There are many differences between healthy tissue and growing tumor tissue, including metabolic, structural and thermodynamic differences. Both structural and thermodynamic differences can be used to follow the entropy differences in cancerous and normal tissue. Entropy production is a bilinear form of the rates of irreversible processes and the corresponding "generalized forces". Entropy production due to various dissipation mechanisms based on temperature differences, chemical potential gradient, chemical affinity, viscous stress and exerted force is a promising tool for calculations relating to potential targets for tumor isolation and demarcation. METHODS: The relative importance of five forms of entropy production was assessed through mathematical estimation. Using our mathematical model we demonstrated that the rate of entropy production by a cancerous cell is always higher than that of a healthy cell apart from the case of the application of external energy. Different rates of entropy production by two kinds of cells influence the direction of entropy flow between the cells. Entropy flow from a cancerous cell to a healthy cell transfers information regarding the cancerous cell and propagates its invasive action to the healthy tissues. To change the direction of entropy flow, in addition to designing certain biochemical pathways to reduce the rate of entropy production by cancerous cells, we suggest supplying external energy to the tumor area, changing the relative rate of entropy production by the two kinds of cells and leading to a higher entropy accumulation in the surrounding normal cells than in the tumorous cells. CONCLUSION: Through the use of mathematical models it was quantitatively demonstrated that when no external force field is applied, the rate of entropy production of cancerous cells is always higher than that of healthy cells. However, when the external energy of square wave electric pulses is applied to tissues, the rate of entropy production of normal cells may exceed that of cancerous cells. Consequently, the application of external energy to the body can reverse the direction of the entropy current. The harmful effect brought about by the entropy flow from cancerous to healthy tissue can be blocked by the reversed direction of entropy current from the irradiated normal tissue around the tumor

A teljesexom-szekvenálás jelentősége a ritka neurológiai betegségek diagnosztikájában – saját tapasztalatok egy ataxiás eset kapcsán

Next generation sequencing (NGS) technologies reshape the diagnostics of rare neurological diseases. In the background of certain neurological symptoms, such as ataxia, many acquired and genetic causes may be present. Variations in a given gene can present with variable phenotypes, too. Because of this phenomenon, the conventional one gene sequencing approach often fails to identify the genetic background of a disease. Next generation sequencing panels allow to sequence 50-100 genes simultaneously, and if the disease stratification is not possible based on the clinical symptoms, whole exome sequencing can help in the diagnostic of genetic disorders with atypical presentation. This case study is about the exome sequencing of a patient with cerebellar ataxia. Genetic investigations identified rare variants in the SPG11 gene in association with the clinical phenotype, which gene was originally described in the background of hereditary spastic paraparesis. Our article highlights that in certain cases the variability of the leading presenting symptom makes it hard to select the correct gene panel. In our case the variants in the gene, formerly associated to hereditary spastic paraparesis, resulted in cerebellar ataxia initially, so even an ataxia NGS gene panel would not detect those. Orv Hetil. 2018; 159(28): 1163-1169

Tooth wear: the view of the anthropologist

Anthropologists have for many years considered human tooth wear a normal physiological phenomenon where teeth, although worn, remain functional throughout life. Wear was considered pathological only if pulpal exposure or premature tooth loss occurred. In addition, adaptive changes to the stomatognathic system in response to wear have been reported including continual eruption, the widening of the masticatory cycle, remodelling of the temporomandibular joint and the shortening of the dental arches from tooth migration. Comparative studies of many different species have also documented these physiological processes supporting the idea of perpetual change over time. In particular, differential wear between enamel and dentine was considered a physiological process relating to the evolution of the form and function of teeth. Although evidence of attrition and abrasion has been known to exist among hunter-gatherer populations for many thousands of years, the prevalence of erosion in such early populations seems insignificant. In particular, non-carious cervical lesions to date have not been observed within these populations and therefore should be viewed as ‘modern-day’ pathology. Extrapolating this anthropological perspective to the clinical setting has merits, particularly in the prevention of pre-mature unnecessary treatment

Type-selective muscular degeneration promotes infiltrative growth of intramuscular lipoma

BACKGROUND: Intramuscular lipoma is a relatively common benign neoplasm that is occasionally described as an infiltrating lipoma. Typical benign tumors show a clear margin, however, the infiltrative growth pattern of this lipoma mimics that of a malignant tumor. Although its growth has an effect on muscle bundles and it is known to never metastasize, the mechanism of infiltrative growth is not well understood. Previously, little attention has been paid to pathogenic features of muscle fibers around an intramuscular lipoma. METHODS: In the present study, we focused on pathologic changes of the surrounding skeletal muscles especially to the degenerative features of involving muscular types, and evaluate the role of type-selective muscular degeneration for the infiltrative growth of intramuscular lipomas. Following a review of the medical records in our institute, 17 lesions containing muscle tissues in their specimens (15 infiltrating lipomas, 2 well-circumscribed lipomas) were analyzed immunohistochemically. The tumor from the most recent case was also subjected to ultrastructural analysis. Two cases of the traumatic muscle damage were also evaluated as the control experiments. RESULTS: These analyses revealed type-selective muscle involution in 11 of 17 intramuscular lipomas and in 10 of 11 of the infiltrative type, with an involving pattern that resembled that of a neurogenic or myogenic disorder. Immunoreactivity to cathepsin-D, a lysosomal catabolic enzyme, was increased in the involved muscle fibers. Subsarcolemmal vacuoles in the muscle fibers of the peripheral areas were also positive for cathepsin-D, while degenerative findings were not visually apparent in these areas. Ultrastructural analysis revealed degenerative changes in those fibers. Neither positive staining for cathepsin-D nor type-selective atrophy was detected in the sections of traumatic muscle damage. CONCLUSIONS: Our findings suggest that type-selective muscular degeneration and endomysial fatty growth as a result of atrophy may modulate the infiltrating growth characteristic of intramuscular lipoma

Prioritising surveillance for alien organisms transported as stowaways on ships travelling to South Africa

The global shipping network facilitates the transportation and introduction of marine and terrestrial organisms to regions where they are not native, and some of these organisms become invasive. South Africa was used as a case study to evaluate the potential for shipping to contribute to the introduction and establishment of marine and terrestrial alien species (i.e. establishment debt) and to assess how this varies across shipping routes and seasons. As a proxy for the number of species introduced (i.e. 'colonisation pressure') shipping movement data were used to determine, for each season, the number of ships that visited South African ports from foreign ports and the number of days travelled between ports. Seasonal marine and terrestrial environmental similarity between South African and foreign ports was then used to estimate the likelihood that introduced species would establish. These data were used to determine the seasonal relative contribution of shipping routes to South Africa's marine and terrestrial establishment debt. Additionally, distribution data were used to identify marine and terrestrial species that are known to be invasive elsewhere and which might be introduced to each South African port through shipping routes that have a high relative contribution to establishment debt. Shipping routes from Asian ports, especially Singapore, have a particularly high relative contribution to South Africa's establishment debt, while among South African ports, Durban has the highest risk of being invaded. There was seasonal variation in the shipping routes that have a high relative contribution to the establishment debt of the South African ports. The presented method provides a simple way to prioritise surveillance effort and our results indicate that, for South Africa, port-specific prevention strategies should be developed, a large portion of the available resources should be allocated to Durban, and seasonal variations and their consequences for prevention strategies should be explored further. (Résumé d'auteur

Evidence of Combat in Triceratops

Background: The horns and frill of Triceratops and other ceratopsids (horned dinosaurs) are interpreted variously as display structures or as weapons against conspecifics and predators. Lesions (in the form of periosteal reactive bone, healing fractures, and alleged punctures) on Triceratops skulls have been used as anecdotal support of intraspecific combat similar to that in modern horned and antlered animals. If ceratopsids with different cranial morphologies used their horns in such combat, this should be reflected in the rates of lesion occurrence across the skull. Methodology/Principal Findings: We used a G-test of independence to compare incidence rates of lesions in Triceratops (which possesses two large brow horns and a smaller nasal horn) and the related ceratopsid Centrosaurus (with a large nasal horn and small brow horns), for the nasal, jugal, squamosal, and parietal bones of the skull. The two taxa differ significantly in the occurrence of lesions on the squamosal bone of the frill (P = 0.002), but not in other cranial bones (P.0.20). Conclusions/Significance: This pattern is consistent with Triceratops using its horns in combat and the frill being adapted as a protective structure for this taxon. Lower pathology rates in Centrosaurus may indicate visual rather than physical use o

Finality revived: powers and intentionality

Proponents of physical intentionality argue that the classic hallmarks of intentionality highlighted by Brentano are also found in purely physical powers. Critics worry that this idea is metaphysically obscure at best, and at worst leads to panpsychism or animism. I examine the debate in detail, finding both confusion and illumination in the physical intentionalist thesis. Analysing a number of the canonical features of intentionality, I show that they all point to one overarching phenomenon of which both the mental and the physical are kinds, namely finality. This is the finality of ‘final causes’, the long-discarded idea of universal action for an end to which recent proponents of physical intentionality are in fact pointing whether or not they realise it. I explain finality in terms of the concept of specific indifference, arguing that in the case of the mental, specific indifference is realised by the process of abstraction, which has no correlate in the case of physical powers. This analysis, I conclude, reveals both the strength and weakness of rational creatures such as us, as well as demystifying (albeit only partly) the way in which powers work

The rs13388259 Intergenic Polymorphism in the Genomic Context of the BCYRN1 Gene Is Associated with Parkinson’s Disease in the Hungarian Population

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by bradykinesia, resting tremor, and muscle rigidity. To date, approximately 50 genes have been implicated in PD pathogenesis, including both Mendelian genes with rare mutations and low-penetrance genes with common polymorphisms. Previous studies of low-penetrance genes focused on protein-coding genes, and less attention was given to long noncoding RNAs (lncRNAs). In this study, we aimed to investigate the susceptibility roles of lncRNA gene polymorphisms in the development of PD. Therefore, polymorphisms (n = 15) of the PINK1-AS, UCHL1-AS, BCYRN1, SOX2-OT, ANRIL and HAR1A lncRNAs genes were genotyped in Hungarian PD patients (n = 160) and age- and sex-matched controls (n = 167). The rare allele of the rs13388259 intergenic polymorphism, located downstream of the BCYRN1 gene, was significantly more frequent among PD patients than control individuals (OR = 2.31; p = 0.0015). In silico prediction suggested that this polymorphism is located in a noncoding region close to the binding site of the transcription factor HNF4A, which is a central regulatory hub gene that has been shown to be upregulated in the peripheral blood of PD patients. The rs13388259 polymorphism may interfere with the binding affinity of transcription factor HNF4A, potentially resulting in abnormal expression of target genes, such as BCYRN1

Lung abscess predicts the surgical outcome in patients with pleural empyema

<p>Abstract</p> <p>Objectives</p> <p>Most cases of pleural empyema are caused by pulmonary infections, which are usually combined with pneumonia or lung abscess. The mortality of patients with pleural empyema remains high (up to 20%). It also contributes to higher hospital costs and longer hospital stays. We studied pleural empyema with combined lung abscess to determine if abscess was associated with mortality.</p> <p>Methods</p> <p>From January 2004 to December 2006, we retrospectively reviewed 259 patients diagnosed with pleural empyema who received thoracscopic decortications of the pleura in a single medical center. We evaluated their clinical data and analyzed their chest computed tomography scans. Outcomes of pleural empyema were compared between groups with and without lung abscess.</p> <p>Results</p> <p>Twenty-two pleural empyema patients had lung abscesses. Clinical data showed significantly higher incidences in the lung abscess group of pre-operative leukocytosis, need for an intensive care unit stay and mortality.</p> <p>Conclusion</p> <p>Patients with pleural empyema and lung abscess have higher intensive care unit admission rate, higher mortality during 30 days and overall mortality than patients with pleural empyema. The odds ratio of lung abscess is 4.685. Physician shall pay more attention on high risk patient of lung abscess for early detection and management.</p