Pharmacological PINK1 activation ameliorates Pathology in Parkinson's Disease models.

PINK1 loss-of-function mutations and exposure to mitochondrial toxins are causative for Parkinson's disease (PD) and Parkinsonism, respectively. We demonstrate that pathological α-synuclein deposition, the hallmark pathology of idiopathic PD, induces mitochondrial dysfunction, and impairs mitophagy as evidenced by the accumulation of the PINK1 substrate pS65-Ubiquitin (pUb). We discovered MTK458, a brain penetrant small molecule that binds to PINK1 and stabilizes its active complex, resulting in increased rates of mitophagy.

Pharmacological PINK1 activation ameliorates Pathology in Parkinson's Disease models.

Unlabelled: PINK1 loss-of-function mutations and exposure to mitochondrial toxins are causative for Parkinson's disease (PD) and Parkinsonism, respectively. We demonstrate that pathological α-synuclein deposition, the hallmark pathology of idiopathic PD, induces mitochondrial dysfunction and impairs mitophagy, driving accumulation of the PINK1 substrate pS65-Ubiquitin (pUb) in primary neurons and in vivo. We synthesized MTK458, a brain penetrant small molecule that binds to PINK1 and stabilizes an active heterocomplex, thereby increasing mitophagy.

Long-term oral kinetin does not protect against α-synuclein-induced neurodegeneration in rodent models of Parkinson's disease.

Mutations in the mitochondrial kinase PTEN-induced putative kinase 1 (PINK1) cause Parkinson's disease (PD), likely by disrupting PINK1's kinase activity. Although the mechanism(s) underlying how this loss of activity causes degeneration remains unclear, increasing PINK1 activity may therapeutically benefit some forms of PD. However, we must first learn whether restoring PINK1 function prevents degeneration in patients harboring PINK1 mutations, or whether boosting PINK1 function can offer protection in more common causes of PD.

A Case of Gastro-Duodenal Artery Aneurism: Treatment and Complications.

We present the case of a 75-year-old patient with asymptomatic gastro-duodenal artery aneurism (GAA) that was coiled through the left femoral artery. The gastro-duodenal artery (GDA) was then embolized. Following the intervention, the patient'™s left foot became cold.

Internal hernia through the foramen of Winslow: a diagnosis to consider in moderate epigastric pain.

Herniation through the foramen of Winslow is a rare condition that can lead to a delayed diagnosis and treatment with a high mortality rate. In most reported cases, patients present to the emergency department with symptoms suggesting intestinal obstruction or with sudden and severe pain in the upper abdomen. Symptoms are non-specific.

The inverted periosteal graft.

The adult human periosteum is known to contain fibroblasts and their progenitor cells, osteoblasts and their progenitor cells, and stem cells. In all age groups, the cells of the periosteum retain the ability to differentiate into fibroblasts, osteoblasts, chondrocytes, adipocytes, and skeletal myocytes. The tissues produced by these cells include cementum with periodontal ligament fibers and bone.

[Spontaneous intraperitoneal hemorrhage: etiology].

Spontaneous intraperitoneal hemorrhage is a rare and sometime fatal condition. The clinical presentation may range from a non-specific abdominal pain to an acute abdomen with hemodynamic instability. Often, a preoperative diagnosis cannot be obtained.

The doctor's view on education and training aspects of secure communication.

Using two examples of installed applications that are widely spread in a large teaching hospital, the awareness of secure communication is highlighted. Teaching to the rotating medical staff is organised on a regular basis. The physicians learn the responsibility they accept when entering the hospital information system (HIS).

Technical means for securing health information.

Securing health information is an application domain which can learn more from other environments like airlines and banking than from military formalism or academic freedom. The techniques of the 80s using clear separation between public and private areas have to be upgraded. Propositions are made.

The technical conditions for an open architecture.

The development of Open Systems Architecture and the extensive networked interconnection of Health and Hospital Information Systems (HIS) offer great opportunities for improved care, but simultaneously these facilities pose a great danger to the overall security of the information held. The Geneva University Hospital which has built up it centralized informatics system over the last twenty years must now bring about the conditions for a migration towards open system, for although during the last ten years there have been declarations of intent, this architecture is still a long way from final implementation. Like others, the DIOGENE system (the Geneva HIS) has had to face difficult choices especially due to its own successful situation at the end of the eighties.

[Holmium:YAG laser in surgical practice in a multidisciplinary hospital center].

The Holmium:YAG laser has been in use at the regional hospital of Montreux, Switzerland. A balance has been drawn at the end of 9 months. 68 surgical operations have been performed; 23 in abdominal surgery, mainly through laparoscopy, and 45 in orthopaedics using scopic viewing.

A double-blind comparison of nimesulide and mefenamic acid in the treatment of acute upper respiratory tract infections in children.

The efficacy and safety of nimesulide suspension were evaluated in comparison with mefenamic acid in a double-blind multicentre study that recruited 100 children with acute respiratory tract infections. On entry, each child was randomly allocated to receive either nimesulide 5 mg/kg/day or mefenamic acid 5 mg/kg divided into 2 or 3 daily doses as an oral suspension, for a period of 3 to 10 days. Body temperature returned to normal on the third day for most of the nimesulide-treated patients, but only on the fifth day for the mefenamic acid group.