TRPML1 links lysosomal calcium to autophagosome biogenesis through the activation of the CaMKKß/VPS34 pathway.

The lysosomal calcium channel TRPML1, whose mutations cause the lysosomal storage disorder (LSD) mucolipidosis type IV (MLIV), contributes to upregulate autophagic genes by inducing the nuclear translocation of the transcription factor EB (TFEB). Here we show that TRPML1 activation also induces autophagic vesicle (AV) biogenesis through the generation of phosphatidylinositol 3-phosphate (PI3P) and the recruitment of essential PI3P-binding proteins to the nascent phagophore in a TFEB-independent manner. Thus, TRPML1 activation of phagophore formation requires the calcium-dependent kinase CaMKKß and AMPK, which increase the activation of ULK1 and VPS34 autophagic protein complexes. Consistently, cells from MLIV patients show a reduced recruitment of PI3P-binding proteins to the phagophore during autophagy induction, suggesting that altered AV biogenesis is part of the pathological features of this disease. Together, we show that TRPML1 is a multistep regulator of autophagy that may be targeted for therapeutic purposes to treat LSDs and other autophagic disorders.

["Acute scrotum" caused by torsion of the hydatid of Morgagni]. / "Scroto acuto" da torsione dell'idatide del Morgagni.

By "acute scrotum" is meant a sudden, painful tumefaction in one or both testicles with local and systemic symptomatologies. It can be caused by spermatic cord torsion in about 50% of cases in paediatric age, while in adults such a cause is much rarer. In addition to the clinical examination, Doppler, eco colour-Doppler and scintigraphy with 99mTc pertecnetate may be of use even though these investigations are not often immediately employable. In addition, as the hours pass, the damage caused to the gonad becomes irreversible; this, of course, influences therapeutic conduct. Starting from the description of a recently observed case of torsion of Morgagni's hydatid, the authors discuss the importance of differential diagnosis to protect the vitality of the testicle and show that surgical exploration, in cases where a definite aetiological diagnosis is missing, is the preferable and most rational therapeutic choice.

[Postoperative chylous ascites: its etiology and treatment]. / Ascite chilosa post-operatoria: etiologia e trattamento.

Postoperative chylous ascites is a rare clinical condition that occurs as a consequence of disruption of the abdominal lymphatics after retroperitoneal dissection. Generally the management is conservative based on a low fat diet and total parenteral hyperalimentation. However, such therapy requires weeks to months before resolution of the ascites. On the other hand, surgical approach is associated with a high failure rate to ligate leaky lymphatics. The Authors, therefore suggest a surgical resolution of the ascite with the use of fibrin glue to occlude rapidly and permanently the lymphatics ruptured.