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Concept: Strange Case of Dr Jekyll and Mr Hyde



Protein misfolding results in devastating degenerative diseases and cancer. Among the culprits involved in these illnesses are prions and prion-like proteins, which can propagate by converting normal proteins to the wrong conformation. For spongiform encephalopathies, a real prion can be transmitted among individuals. In other disorders, the bona fide prion characteristics are still under investigation. Besides inducing misfolding of native proteins, prions bind nucleic acids and other polyanions. Here, we discuss how nucleic-acid binding might influence protein misfolding for both disease-related and benign, functional prions and why the line between bad and good amyloids might be more subtle than previously thought.

Concepts: Proteins, Amyloid, Strange Case of Dr Jekyll and Mr Hyde, Infectious disease, Protein, Prion, Protein folding, Transmissible spongiform encephalopathy


Abstract Objective. To explore factors and circumstances contributing to prudent antibiotic prescribing for respiratory tract infections in primary care. Design. Two focus groups representing rural and urban areas. A semi-structured interview guide with open-ended questions and an editing analysis style was used. They were examined to identify meaning units that were sorted into categories in an iterative process throughout the analysis. Setting. Primary health care in two counties in southern Sweden. Subjects. Two groups including seven and six general practitioners (GPs) respectively, men and women of different ages with different professional experiences. Main outcome measures. Exploration of categories, determination of themes, construction of models. Results. The decision to prescribe antibiotics takes place in the encounter between GP and patient, initially characterized by harmony or fight and the subsequent process by collaboration or negotiation, resulting in agreement, compromise, or disagreement. Several factors influence the meeting and contribute to enhancing the conditions for rational prescribing. These conditions are connected to the GP, the relationship, and the setting; organization as well as professional culture. The findings indicate synergies between the factors, and that one factor can sometimes compensate for lack of another. Continuity and mutual trust can make a brief consultation successful, but lack of continuity can eliminate the effects of knowledge and professional skills. Conclusions. The findings emphasize the importance of the encounter between the GP and the patient for prudent antibiotic prescribing. Furthermore, the importance of an appropriate organization of primary care, which promotes continuity and encourages professional autonomy, is demonstrated.

Concepts: Primary care, Edinburgh, Qualitative research, Strange Case of Dr Jekyll and Mr Hyde, General practitioner, Focus group


This review summarizes the (patho)-physiological effects of ventilation with high FiO2 (0.8-1.0), with a special focus on the most recent clinical evidence on its use for the management of circulatory shock and during medical emergencies. Hyperoxia is a cornerstone of the acute management of circulatory shock, a concept which is based on compelling experimental evidence that compensating the imbalance between O2 supply and requirements (i.e., the oxygen dept) is crucial for survival, at least after trauma. On the other hand, “oxygen toxicity” due to the increased formation of reactive oxygen species limits its use, because it may cause serious deleterious side effects, especially in conditions of ischemia/reperfusion. While these effects are particularly pronounced during long-term administration, i.e., beyond 12-24 h, several retrospective studies suggest that even hyperoxemia of shorter duration is also associated with increased mortality and morbidity. In fact, albeit the clinical evidence from prospective studies is surprisingly scarce, a recent meta-analysis suggests that hyperoxia is associated with increased mortality at least in patients after cardiac arrest, stroke, and traumatic brain injury. Most of these data, however, originate from heterogenous, observational studies with inconsistent results, and therefore, there is a need for the results from the large scale, randomized, controlled clinical trials on the use of hyperoxia, which can be anticipated within the next 2-3 years. Consequently, until then, “conservative” O2 therapy, i.e., targeting an arterial hemoglobin O2 saturation of 88-95 % as suggested by the guidelines of the ARDS Network and the Surviving Sepsis Campaign, represents the treatment of choice to avoid exposure to both hypoxemia and excess hyperoxemia.

Concepts: Mechanical ventilation, Medical emergencies, Traumatic brain injury, Strange Case of Dr Jekyll and Mr Hyde, Cardiac arrest, Stroke, Intensive care medicine, Oxygen


It is known that lactate accumulates in the skeletal muscle during intense anaerobic exercise but is rapidly cleared from the muscles when they resume aerobic metabolism; however, at least some lactate reaches the blood stream. It has been observed that during maximal exercise, blood lactate increases with transport of the blood to the brain. This could be interpreted as a mechanism to protect against possible “central fatigue” in times of maximal activity during the course of which the lactate would preserve the functionality of the primary cortical motor and sensory areas, even at the expense of the efficiency of the other structures. In this way, the role of lactate, both at the muscular level and in the CNS, appears to shift from being responsible for fatigue to protector from fatigue, which represents a real transition similar to that of how the image of Mr. Hyde changes to that of Dr. Jekyll.

Concepts: Muscular system, Glycogen, Metabolism, Strange Case of Dr Jekyll and Mr Hyde, Heart, Muscle, Lactic acid, Exercise physiology


Henry and Martin (2017) and Hartwig et al. (2017) provide more insights into the non-apoptotic function of the FADD/caspase-8 duo in TRAIL signaling.

Concepts: Life, Strange Case of Dr Jekyll and Mr Hyde


During the last decade, a new view into the molecular mechanisms of chronic kidney disease-mineral bone disorder (CKD-MBD) has been proposed, with fibroblast growth factor 23 (FGF23) as a novel player in the field. Enhanced serum FGF23 levels cause a reduction in serum phosphate, together with calcitriol suppression and consequent hyperparathyroidism (HPT). In contrast, reduced serum FGF23 levels are associated with hyperphosphatemia, higher calcitriol levels and parathyroid hormone (PTH) suppression. In addition, serum FGF23 levels are greatly increased and positively correlated with serum phosphate levels in CKD patients. In this population, high serum FGF23 concentration seems to predict the occurrence of refractory secondary HPT and to be associated with higher mortality risk in incident haemodialysis patients. In living-donor kidney transplant recipients, a faster normalization of FGF23 and phosphate levels with a lower prevalence of HPT, may be considered a major pathway to investigate.

Concepts: Calcitonin, Hypoparathyroidism, Parathyroid gland, Vitamin D, Parathyroid hormone, Chronic kidney disease, Hyperparathyroidism, Strange Case of Dr Jekyll and Mr Hyde


p62/SQSTM1 is a multifunctional signaling hub and autophagy adaptor with many binding partners, which allow it to activate mTORC1-dependent nutrient sensing, NF-κB-mediated inflammatory responses and the NRF2-activated antioxidant defense. p62 recognizes polyubiquitin chains via its C-terminal domain and binds to LC3 via its LIR motif, thereby promoting the autophagic degradation of ubiquitinated cargos. p62 accumulates in many human liver diseases, including non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC), where it is a component of Mallory-Denk bodies and intracellular hyaline bodies. Chronic p62 elevation contributes to HCC development by preventing oncogene-induced senescence and death of cancer-initiating cells and enhancing their proliferation. In this review, we discuss p62-mediated signaling pathways and the roles of p62 in liver pathophysiology, especially NASH and HCC. This article is protected by copyright. All rights reserved.

Concepts: Liver transplantation, All rights reserved, Copyright, Hepatitis C, Strange Case of Dr Jekyll and Mr Hyde, Hepatitis, Cirrhosis, Cancer


In their article in this issue of Molecular Ecology, Jenkinson et al. () and colleagues address a worrying question-how could arguably the most dangerous pathogen known to science, Batrachochytrium dendrobatidis (Bd), become even more virulent? The answer: start having sex. Jenkinson et al. present a case for how the introduction into Brazil of the globally invasive lineage of Bd, BdGPL, has disrupted the relationship between native amphibians and an endemic Bd lineage, BdBrazil. BdBrazil is hypothesized to be native to the Atlantic Forest and so have a long co-evolutionary history with biodiverse Atlantic Forest amphibian community. The authors suggest that this has resulted in a zone of hybrid Bd genotypes which are potentially more likely to cause fatal chytridiomycosis than either parent lineage. The endemic-nonendemic Bd hybrid genotypes described in this study, and the evidence for pathogen translocation via the global amphibian trade presented, highlights the danger of anthropogenic pathogen dispersal. This research emphasizes that biosecurity regulations may have to refocus on lineages within species if we are to mitigate against the danger of new, possibly hypervirulent genotypes of pathogens emerging as phylogeographic barriers are breached.

Concepts: Atlantic Forest, Sustainability, Strange Case of Dr Jekyll and Mr Hyde, Ecology, Evolution, Batrachochytrium dendrobatidis, Biodiversity, Brazil


Like the story of Jekyll and Hyde, Th17 cells have two guises. One helps with host immunity, but the other can cause immunopathology. In this issue of Immunity, Dong and colleagues report that three microRNAs, miR-183, miR-96, and miR-182, can enhance the pathogenicity of Th17 cells (Ichiyama et al., 2016).

Concepts: Strange Case of Dr Jekyll and Mr Hyde