Imbibition in Disordered Media

The physics of liquids in porous media gives rise to many interesting phenomena, including imbibition where a viscous fluid displaces a less viscous one. Here we discuss the theoretical and experimental progress made in recent years in this field. The emphasis is on an interfacial description, akin to the focus of a statistical physics approach. Coarse-grained equations of motion have been recently presented in the literature. These contain terms that take into account the pertinent features of imbibition: non-locality and the quenched noise that arises from the random environment, fluctuations of the fluid flow and capillary forces. The theoretical progress has highlighted the presence of intrinsic length-scales that invalidate scale invariance often assumed to be present in kinetic roughening processes such as that of a two-phase boundary in liquid penetration. Another important fact is that the macroscopic fluid flow, the kinetic roughening properties, and the effective noise in the problem are all coupled. Many possible deviations from simple scaling behaviour exist, and we outline the experimental evidence. Finally, prospects for further work, both theoretical and experimental, are discussed.Comment: Review article, to appear in Advances in Physics, 53 pages LaTe

Apolipoprotein E: Isoform Specific Differences in Tertiary Structure and Interaction with Amyloid-β in Human Alzheimer Brain

We applied a novel application of FLIM-FRET to in situ measurement and quantification of protein interactions to explore isoform specific differences in Aβ-ApoE interaction and ApoE tertiary conformation in senile plaques in human Alzheimer brain. ApoE3 interacts more closely with Aβ than ApoE4, but a greater proportion of Aβ molecules within plaques are decorated with ApoE4 than ApoE3, lending strong support to the hypothesis that isoform specific differences in ApoE are linked with Aβ deposition. We found an increased number of ApoE N-terminal fragments in ApoE4 plaques, consistent with the observation that ApoE4 is more easily cleaved than ApoE3. In addition, we measured a small but significant isoform specific difference in ApoE domain interaction. Based on our in situ data, supported by traditional biochemical data, we propose a pathway by which isoform specific conformational differences increase the level of cleavage at the hinge region of ApoE4, leading to a loss of ApoE function to mediate clearance of Aβ and thereby increase the risk of AD for carriers of the APOEε4 allele

Clinical chronobiology: a timely consideration in critical care medicine

A fundamental aspect of human physiology is its cyclical nature over a 24-h period, a feature conserved across most life on Earth. Organisms compartmentalise processes with respect to time in order to promote survival, in a manner that mirrors the rotation of the planet and accompanying diurnal cycles of light and darkness. The influence of circadian rhythms can no longer be overlooked in clinical settings; this review provides intensivists with an up-to-date understanding of the burgeoning field of chronobiology, and suggests ways to incorporate these concepts into daily practice to improve patient outcomes. We outline the function of molecular clocks in remote tissues, which adjust cellular and global physiological function according to the time of day, and the potential clinical advantages to keeping in time with them. We highlight the consequences of "chronopathology", when this harmony is lost, and the risk factors for this condition in critically ill patients. We introduce the concept of "chronofitness" as a new target in the treatment of critical illness: preserving the internal synchronisation of clocks in different tissues, as well as external synchronisation with the environment. We describe methods for monitoring circadian rhythms in a clinical setting, and how this technology may be used for identifying optimal time windows for interventions, or to alert the physician to a critical deterioration of circadian rhythmicity. We suggest a chronobiological approach to critical illness, involving multicomponent strategies to promote chronofitness (chronobundles), and further investment in the development of personalised, time-based treatment for critically ill patients

Recent Advances in Preventing and Managing Postoperative Delirium [version 1; peer review: 2 approved]

Postoperative delirium is a common and harrowing complication in older surgical patients. Those with cognitive impairment or dementia are at especially high risk for developing postoperative delirium; ominously, it is hypothesized that delirium can accelerate cognitive decline and the onset of dementia, or worsen the severity of dementia. Awareness of delirium has grown in recent years as various medical societies have launched initiatives to prevent postoperative delirium and alleviate its impact. Unfortunately, delirium pathophysiology is not well understood and this likely contributes to the current state of low-quality evidence that informs perioperative guidelines. Along these lines, recent prevention trials involving ketamine and dexmedetomidine have demonstrated inconsistent findings. Non-pharmacologic multicomponent initiatives, such as the Hospital Elder Life Program, have consistently reduced delirium incidence and burden across various hospital settings. However, a substantial portion of delirium occurrences are still not prevented, and effective prevention and management strategies are needed to complement such multicomponent non-pharmacologic therapies. In this narrative review, we examine the current understanding of delirium neurobiology and summarize the present state of prevention and management efforts

Patient Safety in Internal Medicine

AbstractHospital Internal Medicine (IM) is the branch of medicine that deals with the diagnosis and non-surgical treatment of diseases, providing the comprehensive care in the office and in the hospital, managing both common and complex illnesses of adolescents, adults, and the elderly. IM is a key ward for Health National Services. In Italy, for example, about 17.3% of acute patients are discharged from the IM departments. After the epidemiological transition to chronic/degenerative diseases, patients admitted to hospital are often poly-pathological and so requiring a global approach as in IM. As such transition was not associated—with rare exceptions—to hospital re-organization of beds and workforce, IM wards are often overcrowded, burdened by off-wards patients and subjected to high turnover and discharge pressure. All these factors contribute to amplify some traditional clinical risks for patients and health operators. The aim of our review is to describe several potential errors and their prevention strategies, which should be implemented by physicians, nurses, and other healthcare professionals working in IM wards