Practical cancer cachexia management in palliative care - a review of current evidence.

PURPOSE OF REVIEW: To explore the current evidence relating to the practical management of cancer cachexia in palliative care. RECENT FINDINGS: The authors found a growing evidence base including the publication of several expert guidelines since 2020. Guidelines identified the need for individualised nutritional and physical exercise support as the mainstay of cachexia management. Dietician and allied health professional referrals are recommended for the best patient outcomes. Limitations of nutritional support and exercise are acknowledged. Patient outcomes from multimodal anti-cachexia therapy are awaited at this time. Communication about the mechanisms of cachexia and nutritional counselling are identified as ways to reduce distress. Evidence supporting the use of pharmacological agents remains insufficient to make recommendations. Corticosteroids and progestins may be offered for symptom relief in refractory cachexia, taking into consideration well-documented side effects. Emphasis is placed on adequately managing nutritional impact symptoms. A specific role for palliative care clinicians and the use of existing palliative care guidelines in managing cancer cachexia were not identified. SUMMARY: Current evidence recognises the inherently palliative nature of cancer cachexia management, and practical guidance correlates with the tenets of palliative care. Individualised approaches to support nutritional intake, physical exercise and alleviate symptoms that accelerate cachexia processes are currently recommended.

Mechanical Contact Spectroscopy: Characterizing Nanoscale Adhesive Contacts via Thermal Forces.

The adhesion of micro- and nanoparticles to solid substrates immersed in liquids is a problem of great scientific and technological importance. However, the quantitative characterization of such nanoscale adhesive contacts without rupturing them still presents a major experimental challenge. In this article, we introduce mechanical contact spectroscopy (MCS), an experimental technique for the nondestructive probing of particle adhesion in liquid environments. With MCS, the strength of adhesive contacts is inferred from residual position fluctuations of adherent particles excited by thermal forces. In particular, the strength of adhesion is correlated with the standard deviation of the particle lateral position x, with smaller position standard deviations [Formula: see text] indicating higher adhesive strength. For a given combination of particles, substrate, and immersion medium, the adhesion is characterized by the mechanical contact spectrum, which is a histogram of ξ values obtained from tracking an ensemble of adherent particles. Because the energy of thermal excitation at room temperature is very small in comparison to the typical total energy of adhesive contacts, the studied contacts remain in equilibrium during the measurement. Using MCS, we study the adhesion of micrometer-sized particles to planar solid substrates under a wide range of environmental conditions, including liquid immersion media of varying ionic strength and adhesion substrates with different chemical functionality of their surfaces. These experiments provide evidence that MCS is capable of reproducibly detecting minute changes in the particle-substrate work of adhesion while at the same time covering the range of adhesive contact strength relevant in the context of surface chemistry, biology, and microfabrication.

Nanoscopic imaging of thick heterogeneous soft-matter structures in aqueous solution.

Precise nanometre-scale imaging of soft structures at room temperature poses a major challenge to any type of microscopy because fast thermal fluctuations lead to significant motion blur if the position of the structure is measured with insufficient bandwidth. Moreover, precise localization is also affected by optical heterogeneities, which lead to deformations in the imaged local geometry, the severity depending on the sample and its thickness. Here we introduce quantitative thermal noise imaging, a three-dimensional scanning probe technique, as a method for imaging soft, optically heterogeneous and porous matter with submicroscopic spatial resolution in aqueous solution. By imaging both individual microtubules and collagen fibrils in a network, we demonstrate that structures can be localized with a precision of ∼10 nm and that their local dynamics can be quantified with 50 kHz bandwidth and subnanometre amplitudes. Furthermore, we show how image distortions caused by optically dense structures can be corrected for.

Detecting sequential bond formation using three-dimensional thermal fluctuation analysis.

We present a novel experimental method that solves two key problems in nondestructive mechanical studies of small biomolecules at the single-molecule level, namely the confirmation of single-molecule conditions and the discrimination against nonspecific binding. A biotin-avidin ligand-receptor couple is spanned between a glass slide and a 1 microm latex particle using short linker molecules. Optical tweezers are used to initiate bond formation and to follow the particle's thermal position fluctuations with nanometer spatial and microsecond temporal resolution. Here we show that each step in the specific binding process leads to an abrupt change in the magnitude of the particle's thermal position fluctuations, allowing us to count the number of bonds formed one by one. Moreover, three-dimensional position histograms calculated from the particle's fluctuations can be separated into well-defined categories reflecting different binding conditions (single specific, multiple specific, nonspecific). Our method brings quantitative mechanical single-molecule studies to the majority of proteins, paving the way for the investigation of a wide range of phenomena at the single-molecule level.