I first read Davidson 30 years ago: at that time it was already in its 5th edition. A brief comparison shows that it then contained about 440,000 words in 1,100 pages: the current edition has compressed 625,000 words into 800 pages. I think I bought it as a student because it was cheap: but also because it seemed to be comprehensive and straightforward, and I have used it as a basis for my medical knowledge ever since. So I miss some of the old pictures of the acute skin rashes such as scarlet fever: in fact infectious disease has been transferred to the back and genetic factors take the first chapters. But careful linguistic comparison will still uncover the old phrases which some of us know by heart-there are minor changes such as 'alarming reactions to intravenous iron are uncommon, but have occasionally been noted', which becomes 'alarming systemic anaphyllactic reactions can occur'. Sir Stanley Davidson made 'no attempt to describe every rare disease or syndrome, but devoted most of the space available to those disorders most commonly encountered in practice'. I have grown up with successive editions, and have gradually come to appreciate the problems of the authors in the compression of knowledge. Having got to know many of them personally as real people rather than as names I can still recommend the book. It is the essential starting point for the study of internal medicine and for many doctors will remain their base reference work. The present editors have kept up-to-date and been prepared to prune the dead wood. There are many competitors in the market, and the publishers must take care with layout and illustration, although Davidson is still the best value for money. I will continue to recommend it to my clinical students: they will need to read it and know it to pass final MB. Postgraduates will need to remember the facts, but also to be able to place them in a broader perspective. The older consultant will still happily read it, and to get to know the authors themselves is really to complete your medical education. Dr John Macleod and his team have successfully kept alive the primary objective 'to provide a rational and easily comprehensible basis for the practice of medicine'. The book is economical in price and compact in size, but still contains the essential truths for the practice of good medicine.

Davidson's Principles and Practice of Medicine

Social Safety Theory hypothesizes that developing and maintaining friendly social bonds is a fundamental organizing principle of human behavior and that threats to social safety are a critical feature of psychological stressors that increase risk for disease. Central to this formulation is the fact that the human brain and immune system are principally designed to keep the body biologically safe, which they do by continually monitoring and responding to social, physical, and microbial threats in the environment. Because situations involving social conflict, isolation, devaluation, rejection, and exclusion historically increased risk for physical injury and infection, anticipatory neural-immune reactivity to social threat was likely highly conserved. This neurocognitive and immunologic ability for humans to symbolically represent and respond to potentially dangerous social situations is ultimately critical for survival. When sustained, however, this multilevel biological threat response can increase individuals' risk for viral infections and several inflammation-related disease conditions that dominate present-day morbidity and mortality.

https://www.annualreviews.org/doi/pdf/10.1146/annurev-clinpsy-032816-045159

Social Safety Theory: A Biologically Based Evolutionary Perspective on Life Stress, Health, and Behavior

The network structure and biological components of natural extracellular matrix (ECM) are indispensable for promoting tissue regeneration Electrospun nanofibrous scaffolds have been widely used in regenerative medicine to provide structural support for cell growth and tissue regeneration due to their natural ECM mimicking architecture, however, they lack biological functions Extracellular vesicles (EVs) are potent vehicles of intercellular communication due to their ability to transfer RNAs, proteins, and lipids, thereby mediating significant biological functions in different biological systems Matrix-bound nanovesicles (MBVs) are identified as an integral and functional component of ECM bioscaffolds mediating significant regenerative functions Therefore, to engineer EVs modified electrospun scaffolds, mimicking the structure of the natural EV-ECM complex and the physiological interactions between the ECM and EVs, will be attractive and promising in tissue regeneration Previously, using one-bead one-compound (OBOC) combinatorial technology, we identified LLP2A, an integrin α4β1 ligand, which had a strong binding to human placenta-derived mesenchymal stem cells (PMSCs) In this study, we isolated PMSCs derived EVs (PMSC-EVs) and demonstrated they expressed integrin α4β1 and could improve endothelial cell (EC) migration and vascular sprouting in an ex vivo rat aortic ring assay LLP2A treated culture surface significantly improved PMSC-EV attachment, and the PMSC-EV treated culture surface significantly enhanced the expression of angiogenic genes and suppressed apoptotic activity We then developed an approach to enable "Click chemistry" to immobilize LLP2A onto the surface of electrospun scaffolds as a linker to immobilize PMSC-EVs onto the scaffold The PMSC-EV modified electrospun scaffolds significantly promoted EC survival and angiogenic gene expression, such as KDR and TIE2, and suppressed the expression of apoptotic markers, such as caspase 9 and caspase 3 Thus, PMSC-EVs hold promising potential to functionalize biomaterial constructs and improve the vascularization and regenerative potential The EVs modified biomaterial scaffolds can be widely used for different tissue engineering applications

/pdf/extracellular-matrix-mimicking-nanofibrous-scaffolds-1owf2tlfow.pdf

Extracellular Matrix Mimicking Nanofibrous Scaffolds Modified With Mesenchymal Stem Cell-Derived Extracellular Vesicles for Improved Vascularization.

The exciting field of human social genomics provides an evolutionarily informed, multilevel framework for understanding how positive and negative social–environmental experiences affect the genome to impact lifelong health, well-being, behavior, and longevity. In this review, we first summarize common patterns of socially influenced changes in the expression of pro-inflammatory and antiviral immune response genes (e.g., the Conserved Transcriptional Response to Adversity), and the multilevel psychological, neural, and cell signaling pathways by which social factors regulate human gene expression. Second, we examine how these effects are moderated by genetic polymorphisms and the specific types of social–environmental experiences that most strongly affect gene expression and health. Third, we identify positive psychosocial experiences and interventions that have been found to impact gene expression. Finally, we discuss promising opportunities for future research on this topic and how health care providers can use this information to improve patient health and well-being.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/lim2.75

Human social genomics: Concepts, mechanisms, and implications for health

INTRODUCTION The surgically induced fetal lamb model is the most commonly used large animal model of myelomeningocele (MMC) but is subject to variation due to surgical technique during defect creation. MATERIAL AND METHODS Thirty-one fetal lambs underwent creation of the MMC defect, followed by defect repair with either an extracellular matrix (ECM) patch (n = 10) or ECM seeded with placental mesenchymal stromal cells (n = 21). Postnatal hindlimb function was assessed using the Sheep Locomotor Rating (SLR) scale. Postmortem magnetic resonance imaging of the lumbar spine was used to measure the level and degree of spinal angulation, as well as cross-sectional area of remaining vertebral bone. RESULTS Median level of angulation was between the 2nd and 3rd lumbar vertebrae, with a median angle of 24.3 degrees (interquartile range 16.2-35.3). There was a negative correlation between angulation degree and SLR (r = -0.44, p = 0.013). Degree of angulation also negatively correlated with the normalized cross-sectional area of remaining vertebral bone (r = -0.75, p < 0.0001). DISCUSSION Surgical creation of fetal MMC leads to varying severity of spinal angulation in the ovine model, which affects postnatal functional outcomes. Postnatal assessment of spinal angulation aids in standardization of the surgical model of fetal MMC repair.

/pdf/spinal-angulation-a-limitation-of-the-fetal-lamb-model-of-23kdl2dhm3.pdf

Spinal Angulation: A Limitation of the Fetal Lamb Model of Myelomeningocele.

Background Research has suggested that physical pain (e.g., caused by injury) and social pain (e.g., caused by social rejection) are modulated by some of the same biological systems. Consequently, it is possible that acetaminophen, which is commonly used to alleviate physical pain through neurochemical pathways, may have social pain-relieving effects that interact with forgiveness, which reduces social pain through psychological pathways. To date, however, only a few studies have examined how experiences of social pain change over time, and none have examined how acetaminophen and forgiveness interact to influence these effects. Purpose We addressed these issues by investigating how acetaminophen administration and daily forgiveness are associated with experiences of social pain over 21 days. We hypothesized that acetaminophen-related reductions in social pain across the 21-day study period would be greatest on days following high levels of forgiveness. Method To test this hypothesis, we conducted a double-blind, randomized, placebo-controlled trial in which we randomly assigned 42 healthy young adults to an acetaminophen condition (1,000 mg of acetaminophen daily), placebo-control condition (400 mg of potassium daily), or empty-control (no pill) condition. We then assessed their levels of forgiveness and social pain for 20 consecutive days. Results As hypothesized, acetaminophen reduced participants' social pain levels over time but only for those exhibiting high levels of forgiveness (i.e., 18.5% reduction in social pain over 20 days). Conclusions These data are the first to show that forgiveness and acetaminophen have interactive effects on experiences of social pain, which is one of the most common and impactful of all human experiences.

/pdf/alleviating-social-pain-a-double-blind-randomized-placebo-54hgw4ie4l.pdf

Alleviating Social Pain: A Double-Blind, Randomized, Placebo-Controlled Trial of Forgiveness and Acetaminophen.

High density placental mesenchymal stromal cells provide neuronal preservation and improve motor function following in utero treatment of ovine myelomeningocele.

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Alleviating Social Pain: A Double-Blind, Randomized, Placebo-Controlled Trial of Forgiveness and Acetaminophen.

Spinal Angulation: A Limitation of the Fetal Lamb Model of Myelomeningocele.

High density placental mesenchymal stromal cells provide neuronal preservation and improve motor function following in utero treatment of ovine myelomeningocele.