Defensive medicine: It is time to finally slow down an epidemic

Defensive medicine is widespread and practiced the world over, with serious consequences for patients, doctors, and healthcare costs. Even students and residents are exposed to defensive medicine practices and taught to take malpractice liability into consideration when making clinical decisions. Defensive medicine is generally thought to stem from physicians’ perception that they can easily be sued by patients or their relatives who seek compensation for presumed medical errors. However, in our view the growth of defensive medicine should be seen in the context of larger changes in the conception of medicine that have taken place in the last few decades, undermining the patient–physician trust, which has traditionally been the main source of professional satisfaction for physicians. These changes include the following: time directly spent with patients has been overtaken by time devoted to electronic health records and desk work; family doctors have played a progressively less central role; clinical reasoning is being replaced by guidelines and algorithms; the public at large and a number of young physicians tend to believe that medicine is a perfect science rather than an imperfect art, as it continues to be; and modern societies do not tolerate the inevitable morbidity and mortality. To finally reduce the increasing defensive behavior of doctors around the world, the decriminalization of medical errors and the assurance that they can be dealt with in civil courts or by medical organizations in all countries could help but it would not suffice. Physicians and surgeons should be allowed to spend the time they need with their patients and should give clinical reasoning the importance it deserves. The institutions should support the doctors who have experienced adverse patient events, and the media should stop reporting with excessive evidence presumed medical errors and subject physicians to “public trials” before they are eventually judged in court

Liver cirrhosis in sub-Saharan Africa: neglected, yet important

Clinical efforts and research on liver diseases have been scarce in sub-Saharan Africa. The first Conference on Liver Disease in Africa (Nairobi, Sept 13–15, 2018), gathering all stakeholders from the continent, is a welcome step towards greater attention to the problem, and the important issue of liver cirrhosis

Khat-related liver disease in sub-Saharan Africa: neglected, yet important reply

The question of khat's liver toxicity is complex. It contains numerous compounds, including alkaloids, terpenoids, flavonoids, sterols, glycosides, tannins, amino acids, vitamins, and minerals.5 Research into the deleterious effects of khat has largely concentrated on the pharmacological effects of cathinone and cathine on the cardiovascular system and CNS, and studies on possible liver toxicity in humans are restricted to Ethiopia and Somaliland and to reports from western Europe almost exclusively involving Somali men. Additional research is necessary to establish the prevalence of liver toxicity in people who chew khat in Ethiopia versus Djibouti (where liver toxicity is apparently not observed)6 and Yemen (which has the highest proportion of users worldwide),7 and in Kenya, Uganda, and Madagascar, where studies have not been done. Also necessary is investigating the mechanisms and progression of liver damage induced by khat, the effects of gender (khat toxicity is observed much more frequently in males)8 and genetics (genetic variants in CYP2D6 might play a role in liver toxicity),9 and the contribution of other compounds found in khat and of contaminating herbicides and pesticides to liver disease.10 Current evidence shows that hepatitis viruses and alcohol are the main contributors to the incidence of liver cirrhosis throughout sub-Saharan Africa1 and efforts should continue to curb their effects. We declare no competing interests

Flooding Responses on Grapevine: A Physiological, Transcriptional, and Metabolic Perspective

Studies on model plants have shown that temporary soil flooding exposes roots to a significant hypoxic stress resulting in metabolic re-programming, accumulation of toxic metabolites and hormonal imbalance. To date, physiological and transcriptional responses to flooding in grapevine are poorly characterized. To fill this gap, we aimed to gain insights into the transcriptional and metabolic changes induced by flooding on grapevine roots (K5BB rootstocks), on which cv Sauvignon blanc (Vitis vinifera L.) plants were grafted. A preliminary experiment under hydroponic conditions enabled the identification of transiently and steadily regulated hypoxia-responsive marker genes and drafting a model for response to oxygen deprivation in grapevine roots. Afterward, over two consecutive vegetative seasons, flooding was imposed to potted vines during the late dormancy period, to mimick the most frequent waterlogging events occurring in the field. Untargeted transcriptomic and metabolic profiling approaches were applied to investigate early responses of grapevine roots during exposure to hypoxia and subsequent recovery after stress removal. The initial hypoxic response was marked by a significant increase of the hypoxia-inducible metabolites ethanol, GABA, succinic acid and alanine which remained high also 1 week after recovery from flooding with the exception of ethanol that leveled off. Transcriptomic data supported the metabolic changes by indicating a substantial rearrangement of primary metabolic pathways through enhancement of the glycolytic and fermentative enzymes and of a subset of enzymes involved in the TCA cycle. GO and KEGG pathway analyses of differentially expressed genes showed a general down-regulation of brassinosteroid, auxin and gibberellin biosynthesis in waterlogged plants, suggesting a general inhibition of root growth and lateral expansion. During recovery, transcriptional activation of gibberellin biosynthetic genes and down-regulation of the metabolic ones may support a role for gibberellins in signaling grapevine rootstocks waterlogging metabolic and hormonal changes to the above ground plant. The significant internode elongation measured upon budbreak during recovery in plants that had experienced flooding supported this hypothesis. Overall integration of these data enabled us to draft a first comprehensive view of the molecular and metabolic pathways involved in grapevine\u2019s root responses highlighting a deep metabolic and transcriptomic reprogramming during and after exposure to waterlogging

Flooding Responses on Grapevine: A Physiological, Transcriptional, and Metabolic Perspective

Studies on model plants have shown that temporary soil flooding exposes roots to a significant hypoxic stress resulting in metabolic re-programming, accumulation of toxic metabolites and hormonal imbalance. To date, physiological and transcriptional responses to flooding in grapevine are poorly characterized. To fill this gap, we aimed to gain insights into the transcriptional and metabolic changes induced by flooding on grapevine roots (K5BB rootstocks), on which cv Sauvignon blanc (Vitis vinifera L.) plants were grafted. A preliminary experiment under hydroponic conditions enabled the identification of transiently and steadily regulated hypoxia-responsive marker genes and drafting a model for response to oxygen deprivation in grapevine roots. Afterward, over two consecutive vegetative seasons, flooding was imposed to potted vines during the late dormancy period, to mimick the most frequent waterlogging events occurring in the field. Untargeted transcriptomic and metabolic profiling approaches were applied to investigate early responses of grapevine roots during exposure to hypoxia and subsequent recovery after stress removal. The initial hypoxic response was marked by a significant increase of the hypoxia-inducible metabolites ethanol, GABA, succinic acid and alanine which remained high also 1 week after recovery from flooding with the exception of ethanol that leveled off. Transcriptomic data supported the metabolic changes by indicating a substantial rearrangement of primary metabolic pathways through enhancement of the glycolytic and fermentative enzymes and of a subset of enzymes involved in the TCA cycle. GO and KEGG pathway analyses of differentially expressed genes showed a general down-regulation of brassinosteroid, auxin and gibberellin biosynthesis in waterlogged plants, suggesting a general inhibition of root growth and lateral expansion. During recovery, transcriptional activation of gibberellin biosynthetic genes and down-regulation of the metabolic ones may support a role for gibberellins in signaling grapevine rootstocks waterlogging metabolic and hormonal changes to the above ground plant. The significant internode elongation measured upon budbreak during recovery in plants that had experienced flooding supported this hypothesis. Overall integration of these data enabled us to draft a first comprehensive view of the molecular and metabolic pathways involved in grapevine’s root responses highlighting a deep metabolic and transcriptomic reprogramming during and after exposure to waterlogging

Liver diseases in developing countries

Liver diseases are an important and largely neglected health issue in low and middle income countries, which carry the highest burden. In this Topic Highlight, experts review hepatitis B and E, alcoholic liver disease, hepatic diseases in human immunodeficiency virus -infected individuals, hepatocellular carcinoma. Numerous gaps in our knowledge that need to be filled are outlined and feasible solutions to the several problems related to diagnosis and management of liver diseases in developing countries are suggested