Intracranial Angioplasty via Type II Proatlantal Intersegmental Artery.

A proatlantal intersegmental artery (PIA) is an exceedingly rare primitive anastomosis between the carotid and vertebrobasilar circulations. PIAs may be accompanied by ipsilateral or bilateral vertebral artery (VA) agenesis and can originate from the cervical internal carotid artery (ICA, type I) or external carotid artery (ECA, type II) before eventually joining the vertebrobasilar system. Several authors have described this anomaly in different clinical scenarios, but to our knowledge, there are no studies documenting VA angioplasty through a type II PIA in the setting of vertebrobasilar stroke. We present the case of vertebrobasilar stroke in which the right VA did not originate from the right subclavian artery but instead from the ECA. The patient was subsequently determined to have a type II PIA. We performed right VA angioplasty via the PIA, followed by partial restoration of vertebrobasilar blood flow. This is the first documented case of intracranial vertebral angioplasty through a type II PIA and serves as a reminder for neuroendovascular surgeons about persistent fetal circulation. In such instances, an angiogram of both the ICA and ECA should be performed to exclude right VA stenosis and visualize persistent fetal circulation. This case underscores the complexity of arterial thrombotic events, the beneficial role of endovascular intervention, and the necessity of future studies to identify the optimal treatment methods for vertebrobasilar stroke.

Association of early donor chimerism status with survival outcomes in post allogeneic haematopoietic stem cell transplant patients of nonmalignant diseases.

OBJECTIVE: To highlight the association of early donor chimerism status at 2nd month with various survival outcomes. Method: The retrospective study was conducted at the Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan, and comprised patient data from January 2011 to July 2016. Data related to participants who underwent human leukocyte antigen-matched transplants for bone marrow failure syndrome and beta thalassemia major. Short tandem repeat-based polymerase chain reaction was used to assess donor chimerism status. Overall survival, disease-free survival, relapse-free survival, and graft versus host disease-free survival rates were noted. Data was analysed using SPSS 23. RESULTS: Of the 106, 64(60.4%) had bone marrow failure syndrome and 42(39.6%) had beta thalassemia major. The overall median follow-up was 13.53 months (range: 1.81-62.73 months). Early donor chimerism status was associated with overall survival (p=0.02) and disease-free survival (p=0.01). Mixed donor chimerism was less hazardous in terms of overall survival (p=0.04) and disease-free survival (p=0.02). CONCLUSIONS: Early mixed donor chimerism contributed to optimal survival in nonmalignant disease.

Resveratrol-Inspired Bridged Bicyclic Compounds: A New Compound Class for the Protection of Synaptic Function from Acute Oxidative Stress.

While resveratrol protects organisms from the deleterious effects of oxidative stress, its multifarious mechanism of action limits its potential as a selective medicinal agent. To address this shortcoming, we have designed a molecular scaffold that we have termed a resveramorph. The structure of this compound class possesses much of the functional group characteristics of resveratrol but in a nonplanar molecular arrangement, and, in the present work, we probe the neuroprotective activities of two resveramorph analogues. These novel compounds were found to protect neurotransmission from hydrogen peroxide-induced oxidative stress. Our findings demonstrate that, at a subnanomolar level, one analogue, resveramorph 1, protects synaptic transmission from acute oxidative stress at the Drosophila neuromuscular junction. These results position resveramorphs as potential lead compounds in the development of new drugs for neurodegenerative diseases.

BK channels and a cGMP-dependent protein kinase (PKG) function through independent mechanisms to regulate the tolerance of synaptic transmission to acute oxidative stress at the Drosophila larval neuromuscular junction.

A cGMP-dependent protein kinase (PKG) has previously been shown to regulate synaptic transmission at the Drosophila neuromuscular junction (NMJ) during acute oxidative stress, potentially through modulation of downstream K+ channel kinetics; however, the specific K+ channels through which PKG functions remains unclear. In this study, we hypothesized that PKG may be acting on calcium-activated large-conductance Slo K+ channels, or BK channels. We found that genetic elimination and pharmacological inhibition of BK channel conductance increases synaptic transmission tolerance to acute H2O2-induced oxidative stress. Furthermore, we discovered that activation of PKG in BK channel loss-of-function (Slo4) mutants significantly decreases time to stimulus-induced synaptic failure, providing the first evidence of PKG and BK channels functioning independently to control synaptic transmission tolerance to acute oxidative stress.