Surgical impact on brain tumor invasion: A physical perspective

Background

Epidural fibrosis is regarded as a cause of failed back surgery syndrome (FBSS) when excessive adhesional/fibrotic scar tissue causes compression, pain or discomfort by tethering of nerve tissue to the surrounding muscle or bone. Fibrosis inhibitors could therefore increase the success rate of spinal surgery and decrease the need for reoperations. In recent years, bio-resorbable gels or films for the prevention of peridural fibrosis and post-operative adhesions have been developed that look clinically promising. This included a 100% synthetic, sterile, absorbable gel combinations of carboxymethylcellulose (CMC) and polyethylene oxide (PEO) used to coat the dura to reduce scarring after discectomy which became available in Europe in 2002. However, given the burden of the problem and unfavorable experience with other types of adhesion-reduction agents, our unit decided to evaluate the safety of CMC/PEO in a large population of patients undergoing spinal microdiscectomy for herniation.

Methods

To determine the safety and assess efficacy of carboxymethylcellulose/polyethylene oxide (CMC/PEO) gel as an anti-adhesion gel, a consecutive series of 396 patients undergoing lumbar discectomy performed by one surgeon had CMC/PEO gel administered at the end of surgery. The patients were followed up in accordance with standard clinical practice and records reviewed for side effects, such as skin reactions, general reactions or local fluid collections. Reoperations for recurrent herniation included an evaluation of fibrosis reduction.

Results

No product related complications were observed. Five patients needed reoperations for recurrent herniation. Significant but subjective reduction in fibrosis was observed in these patients.

Conclusion

The findings provide confidence that CMC/PEO gel is well tolerated as an agent to achieve reduction of fibrosis in lumbar disc surgery. Further formal prospective study is recommended in this area of unmet need.     

The great transformation: A long-run perspective on physical well-being in Canada

During the 19th century the physical stature of the Canadian-born stagnated or declined slightly in spite of a substantial increase in income. Stature varied regionally within Canada. The Quebec population was especially short; men in the Atlantic coastal region were taller than their low incomes would lead us to expect. Heights increased dramatically in the 20th Century. The pattern of long-run change is consistent with evidence of age-specific mortality and with the relationship between income and physical well-being envisaged by Preston [Preston, S., 1975. The changing relationship between mortality and the level of economic development. Popul. Stud. 29, 231-248]. The transition from stagnant or declining stature to secular increase points to a dramatic shift ca. 1900 in the evolution of the physical standard of living in Canada.     

An evolutionary perspective on human physical activity: implications for health

At present, human genes and human lives are incongruent, especially in affluent Western nations. When our current genome was originally selected, daily physical exertion was obligatory; our biochemistry and physiology are designed to function optimally in such circumstances. However, today's mechanized, technologically oriented conditions allow and even promote an unprecedentedly sedentary lifestyle. Many important health problems are affected by this imbalance, including atherosclerosis, obesity, age-related fractures and diabetes, among others. Most physicians recognize that regular exercise is a critical component of effective health promotion regimens, but there is substantial disagreement about details, most importantly volume: how much daily caloric expenditure, as physical activity, is desirable. Because epidemiology-based recommendations vary, often confusing and alienating the health-conscious public, an independent estimate, arising from a separate scientific discipline, is desirable, at least for purposes of triangulation. The retrojected level of ancestral physical activity might meet this need. The best available such reconstruction suggests that the World Health Organization's recommendation, a physical activity level of 1.75 ( approximately 2.1 MJ (490 kcal)/d), most closely approximates the Paleolithic standard, that for which our genetic makeup was originally selected.     

Prostate cancer radiation therapy: A physician’s perspective

Prostate cancer is the second most common cancer in men and a major cause of cancer deaths worldwide. Ionizing radiation has played a substantial role in the curative treatment of this disease. The historical evolution of radiotherapy techniques through 3D-conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), and image-guided radiotherapy (IGRT) has allowed more accurate and precise treatments toward significant improvements in the therapeutic ratio. The addition of androgen deprivation therapy has significantly improved overall survival becoming the standard therapy for intermediate- and high-risk disease. Many randomized controlled trials have shown improved local control with dose escalation, and hypofractionated RT has been consolidated with proven efficacy and safe clinical results. However, several questions remain open in the radiotherapeutic management of prostate cancer patients and hopefully ongoing studies will shed light on these uncertainties. More individualized approaches are essential through better prognostic and novel predictive biomarkers of prostate radiotherapy response. Clinicians should critically interpret the evolving technologies in prostate cancer radiotherapy with important optimism but balancing the costs and the actual magnitude of clinical benefit. This article provides an overview of the basic aspects of radiotherapy treatment in localized prostate cancer from a physician’s perspective.     

A manipulative test of competing theories for metabolic scaling

The reasons why metabolic rate (B) scales allometrically with body mass (M) remain hotly debated. The field is dominated by correlational analyses of the relationship between B and M; these struggle to disentangle competing explanations because both B and M are confounded with ontogeny, life history, and ecology. Here, we overcome these problems by using an experimental approach to test among competing metabolic theories. We examined the scaling of B in size-manipulated and intact colonies of a bryozoan and show that B scales with M(0.5). To explain this, we apply a general model based on the dynamic energy budget theory for metabolic organization that predicts B on the basis of energy allocation to assimilation, maintenance, growth, and maturation. Uniquely, this model predicts the absolute value of B, emphasizes that there is no single scaling exponent of B, and demonstrates that a single model can explain the variation in B seen in nature.     

The basis for spinal manipulation: Chiropractic perspective of indications and theory

It is reasonable to think that patients responding to spinal manipulation (SM), a mechanically based therapy, would have mechanical derangement of the spine as a critical causal component in the mechanism of their condition. Consequently, SM practitioners routinely assess intervertebral motion, and treat patients on the basis of those assessments. In chiropractic practice, the vertebral subluxation has been the historical raison d'etre for SM. Vertebral subluxation is a biomechanical spine derangement thought to produce clinically significant effects by disturbing neurological function. This paper reviews the putative mechanical features of the subluxation and three theories that form the foundation for much of chiropractic practice. It concludes with discussion of subluxation as an indicator for SM therapy, particularly from the perspective that subluxation may be one contributory cause of ill-health within a "web of causation".     

A twenty year perspective on melanoma therapy

Melanoma had long been considered to be particularly addressable with immunotherapy, but that reputation was built on modestly effective cytokine-based immunotherapy. CTLA-4 antibody therapy reinforced this legacy, but PD-1 antibodies transformed the melanoma treatment landscape and lead the way for immunotherapy to become standard treatment for more than half of the advanced cancer population. BRAF mutations were discovered in 8% of all cancer and nearly 50% of melanomas. Successful development of BRAF inhibitors and BRAF/MEK combination therapy in melanoma preceded regulatory approval across all cancer types. No cancer type saw outcomes improved by the same margin as melanoma in the decade of the 2010s.     

A patient and family perspective on gene therapy for rare diseases

The authors describe the view of patients and patient organisations on gene therapy research and gene therapy regulations. In particular, the added value of partnership between scientists and patient organisations, and patient involvement in the gene therapy field, are addressed.     

Core deformations in protein families: a physical perspective

An analysis is presented on how structural cores change shape within protein families, and whether or not there is a relationship between these structural changes and the vibrational modes that proteins experiment due to topological constraints. A set of 13 representative and well-populated protein families are studied. The evolutionary directions of deformation are obtained by applying a new multiple structural alignment technique to superimpose the structures and extract a conserved core, together with Principal Components Analysis (PCA) to extract the main deformation modes. A low-resolution Normal Mode Analysis (NMA) technique is used in parallel to study the properties of the mechanical core plasticity of the same proteins. We find that the evolutionary deformations span a low dimensional space. A statistically significant correspondence exists between these principal deformations and the vibrational modes accessible to a particular topology. We conclude that, to a significant extent, the structures of evolving proteins seem to respond to sequence changes by collective deformations along combinations of low-frequency modes. The findings have implications in structure prediction by homology modeling.     

To optimize the efficacy of bioheat transfer in capacitive hyperthermia: A physical perspective

This paper presents the capacitive hyperthermia from physical perspective focusing on the geometric dimensions as parameters. For this purpose six parameters having three levels each, including two tunable parameters i.e. applied voltage, frequency together with four geometric parameters i.e. size of the tumor, location of the tumor, electrode size and relative position of the electrodes w.r.t tumor were considered for analysis. Taguchi based design of experiments approach was used for the aforementioned six parameters. Using Taguchi's standard L27 orthogonal array, the required results could be obtained employing least number of experiments. For this study temperature was taken as the quality characteristic to be optimized. Furthermore, analysis of variance (ANOVA) was performed to quantify the effect of each parameter on the response variable and results were presented. To deal with the extent of thermal damage to the healthy tissue and tumor, the fraction of tissue experiencing thermal damage was calculated. For this purpose two indices namely treatment index and damage index were formulated. Finally it was concluded that maximum achieved temperature alone does not depict the effectiveness of the treatment. Rather, the combination of the maximum achieved temperature and accompanied thermal damage to the surrounding healthy tissue which should be considered.     

Modifying enzyme replacement therapy – A perspective

Several diseases are caused by the lack of functional proteins, including lysosomal storage diseases or haemophilia A and B. Patients suffering from one of these diseases are treated via enzyme replacement therapies to restore the missing protein. Although this treatment strategy prevents some disease symptoms, enzyme replacement therapies are very expensive and require very frequent infusions, which can cause infusion adverse reactions and massively impair the quality of life of the patients. This review proposes a technology to sustainably produce proteins within the patient to potentially make frequent protein‐infusions redundant. This technology is based on blood circulating immune cells as producers of the needed therapeutic protein. To ensure a stable protein concentration over time the cells are equipped with a system, which induces cell proliferation when low therapeutic protein levels are detected and a system inhibiting cell proliferation when high therapeutic protein levels are detected.     

Coordinated network functioning in the spinal cord: An evolutionary perspective

The successful achievement of harmonious locomotor movement results from the integrated operation of all body segments. Here, we will review current knowledge on the functional organization of spinal networks involved in mammalian locomotion. Attention will not simply be restricted to hindlimb muscle control, but by also considering the necessarily coordinated activation of trunk and forelimb muscles, we will try to demonstrate that while there has been a progressive increase in locomotor system complexity during evolution, many basic organizational features have been preserved across the spectrum from lower vertebrates through to humans. Concerning the organization of axial neuronal networks that control trunk muscles, it has been found across the vertebrate range that during locomotor movement a motor wave travels longitudinally in the spinal cord via the coupling of rhythmic segmental networks. For hindlimb activation it has been found in all species studied that the rostral lumbar segments contain the key elements for pattern generation. We also showed that rhythmic arm movements are under the control of cervical forelimb generators in quadrupeds as well as in human. Finally, it is highlighted that the coordination of quadrupedal movements during locomotion derives principally from an asymmetrical coordinating influence occurring in the caudo-rostral direction from the lumbar hindlimb networks.