Bedside to bench Alport syndrome research: are human urine‐derived podocytes the answer?†

In a recent issue of The Journal of Pathology, Iampietro et al isolated and characterized several clones of urine‐derived podocytes from three patients with Alport syndrome (AS) and proteinuria and one age‐matched non‐proteinuric control. They reported differential expression of genes involved in cell motility, adhesion, survival, and angiogenesis. The authors found AS podocytes to be less motile and to have significantly higher permeability to albumin compared to control podocytes, highlighting that AS podocytes may retain their phenotype even when losing contact with the glomerular basement membrane. The establishment of urine‐derived podocyte cell lines from patients with different genetic forms of AS may represent a valuable and minimally invasive tool to investigate the cellular mechanisms contributing to kidney disease progression in AS and may allow for the establishment of patient‐specific drug screening opportunities. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

The effect of desire thinking on facilitating beliefs in alcohol use disorder: An experimental investigation

Permissive beliefs relate to the acceptability of engaging in alcohol use in spite of obvious potential negative consequences. They are considered the most proximal and precipitating cognitive factor in the decision to use alcohol and/or the activation of strategies to obtain it. Recent research suggested that ‘desire thinking’ may be involved in the escalation of craving and addictive behaviours and can play a role in strengthening permissive beliefs. The current study tested whether the induction of desire thinking would have a stronger effect on rate of conviction in permissive beliefs compared to a control cognitive response in the form of neutral thinking and whether this effect would be specific for patients with alcohol use disorder (AUD). Thirty AUD patients and 30 social drinkers (SD) were randomly allocated to two thinking manipulation tasks (desire thinking and neutral thinking). Current permissive beliefs were measured before and after manipulation and after a resting phase. Findings showed that desire thinking increased the level of current permissive beliefs after manipulation relative to the neutral thinking condition for the AUD group but not for the SD group. This effect was not purely dependent on the concurrent level of perceived craving. This study supports a causal relationship between the induction of desire thinking and rate of conviction in permissive beliefs and highlights the relevance of targeting desire thinking in the treatment for AUD patients.     

Echocardiography diagnosis of ruptured congenital right coronary sinus of Valsalva aneurysm into right ventricle.

We describe a case of ruptured aneurysm of the right coronary sinus of Valsalva (ASV) diagnosed by transthoracic two-dimensional echocardiography which allowed to quickly establish a correct diagnosis in a patient with a recent onset of continuous murmur and acute right congestive heart failure.     

Identification of New Natural CphA Metallo-β-Lactamases CphA4 and CphA5 in Aeromonas veronii and Aeromonas hydrophila Isolates from Municipal Sewage in Central Italy

Two new natural CphA metallo-β-lactamases, the CphA4 and CphA5 enzymes, were identified in water samples from municipal sewage in central Italy. Compared to CphA, the CphA4 and CphA5 enzymes showed numerous point mutations. These enzymes have a narrow spectrum of substrates focused on carbapenems only. CphA5 showed k_cat values about 40-, 12-, and 97-fold higher than those observed for CphA4 versus imipenem, ertapenem, and biapenem, respectively.     

Sphingomyelinase-Like Phosphodiesterase 3b Expression Levels Determine Podocyte Injury Phenotypes in Glomerular Disease

Diabetic kidney disease (DKD) is the most common cause of ESRD in the United States. Podocyte injury is an important feature of DKD that is likely to be caused by circulating factors other than glucose. Soluble urokinase plasminogen activator receptor (suPAR) is a circulating factor found to be elevated in the serum of patients with FSGS and causes podocyte αVβ₃ integrin-dependent migration in vitro. Furthermore, αVβ₃ integrin activation occurs in association with decreased podocyte-specific expression of acid sphingomyelinase-like phosphodiesterase 3b (SMPDL3b) in kidney biopsy specimens from patients with FSGS. However, whether suPAR-dependent αVβ₃ integrin activation occurs in diseases other than FSGS and whether there is a direct link between circulating suPAR levels and SMPDL3b expression in podocytes remain to be established. Our data indicate that serum suPAR levels are also elevated in patients with DKD. However, unlike in FSGS, SMPDL3b expression was increased in glomeruli from patients with DKD and DKD sera-treated human podocytes, where it prevented αVβ₃ integrin activation by its interaction with suPAR and led to increased RhoA activity, rendering podocytes more susceptible to apoptosis. In vivo, inhibition of acid sphingomyelinase reduced proteinuria in experimental DKD but not FSGS, indicating that SMPDL3b expression levels determined the podocyte injury phenotype. These observations suggest that SMPDL3b may be an important modulator of podocyte function by shifting suPAR-mediated podocyte injury from a migratory phenotype to an apoptotic phenotype and that it represents a novel therapeutic glomerular disease target.