Vol 2-5 Commentary

The role of historical medical archives in the genealogical rebuilding of large families affected by neurodegenerative diseases

 Chiara Cupidi, Valentina Laganà, Nicoletta Smirne, Amalia Cecilia Bruni*

Starting from a proband for whom a family history of neurodegenerative disorder has been reported, clinical and genealogical methods are often used together to reconstruct the pedigree of many large families affected by hereditary diseases.
 
This approach was fundamental in the rebuilding of the N family, the kindred originated from southern Italy affected by early onset autosomal dominant Alzheimer’s disease (AD), that has given an important contribution to the discovery of Presenilin 1, the main gene responsible for AD.
 
The identification of several patients in this pedigree, encompassing 11 generations with several hundred of affected subjects, was achieved through the meticulous study of medical records in the archives of the Provincial Psychiatric Hospital of Girifalco in Italy and in the municipal and parish archives of many towns belonging to the same geographical area. The research on N family triggered several other studies on hereditary neurodegenerative disorders in Southern Italy. Investigation focusing on antique archives and the analysis of phenotypes allowed to reconstruct and clinically detail large pedigrees of hereditary diseases, such as frontotemporal dementia and spinocerebellar ataxia 17, even before the discovery of their causative genes.
 

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Vol 2-5 Commentary

Commentary: Periostin (POSTN) Regulates Tumor Resistance to Antiangiogenic Therapy in Glioma Models

Soon Young Park, Veerakumar Balasubramaniyan, and John F. de Groot*

Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

Glioblastoma (GBM) are highly vascularized, invasive brain tumors with a dismal prognosis. Despite surgical de-bulking of the tumor mass followed by concomitant intensive chemo/radiotherapy, GBM patients exhibit poor survival rates (REF). The hallmark presence of microvascular proliferation in GBM has attracted vast interest in the use of antiangiogenic therapies. Bevacizumab a humanized recombinant monoclonal antibody against VEGF-A was approved by the FDA for the treatment of recurrent GBM. However, several recent studies have reported the lack of a survival benefit suggesting tumors have both intrinsic and acquired resistance to anti-VEGF therapy1,2. Studies suggest mesenchymal transition and hypoxia signaling as two major pathways associated with the development of resistance to anti-VEGF therapy. Recently, we reported that the glioma treated with bevacizumab have higher periostin (POSTN) expression than control tumors in a murine glioma tumor models3. In this commentary, we review our recent findings as well as the role of POSTN in antiangiogenic therapy resistance in glioma.

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Vol 2-5 Commentary

Commentary: Extended-Duration betrixaban reduces the risk of stroke versus standard-Dose enoxaparin among hospitalized medically Ill patients

Tarek Nafee, Dima Nimri, Gerald Chi, Serge Korjian, Yazan Daaboul, Douglas Arbetter, Megan Yee, Purva Jain, Seyedmahdi Pahlavani, Haleigh Williams, Nathan Michalak, Megan Merlo, Usama Talib, C. Michael Gibson*

Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

Stroke is one of the leading causes of mortality and morbidity worldwide. It results in considerable costs to the healthcare system in the United States. Pharmacologic stroke prophylaxis has been well-studied in patients with atrial fibrillation and in patients with a history of stroke. In-hospital strokes constitute 2.2% to 17% of all strokes and often go undiagnosed in acute medically ill patients. A retrospective analysis of the APEX trial identifies an acutely ill hospitalized patient population that may benefit from extended duration prophylaxis. The hospitalized medically ill are a novel population to target for stroke prophylaxis. This article will discuss the primary results of the APEX sub-study and other trials that have demonstrated stroke reduction with extended duration anticoagulation in this population. This article additionally comments on the clinical relevance of these findings and the importance of the development of short-term risk stratification models to aid clinicians in deciding whether or not to provide pharmacologic stroke prophylaxis to their acutely ill patients at hospital admission.

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Vol 2-5 Mini Review

Arterial stiffness and cognitive dysfunction in alzheimer and parkinson's diseases

Yoon-Sang Oh, Dong-Woo Ryu, Jee-Eun Lee, Joong-Seok Kim*

Department of Neurology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

Cognitive dysfunction and dementia are important causes of disability and mortality in the elderly population. Over a decade, many studies have found evidence that greater arterial stiffness is associated with impaired cognitive function. Stiff arteries have a direct effect on the brain microvasculature. In this review, we present evidence that arterial stiffness is linked to cognitive dysfunction in neurodegenerative disorders represented by Alzheimer’s disease and Parkinson’s disease. We also discuss possible mechanisms of arterial stiffness and cognitive dysfunction other than the universal pathologic features of beta-amyloid for Alzheimer’s disease and alpha-synuclein for Parkinson’s disease.

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