Gamma Surgery for Hemangiopericytomas

A retrospective analysis of a consecutive series of 12 patients with 15 intracranial hemangiopericytomas treated at the University of Virginia using Gamma surgery is presented. Clinical and radiographic follow up of 3 to 56 months is available for 10 patients with 12 tumors. There was one tumor present at the time of initial Gamma surgery in each patient. Two new tumors occurred in patients previously treated. Nine of the tumors decreased in volume and three remained stable. Four of the nine tumors that shrank later progressed at an average of 22 months after treatment. Of the tumors that decreased in volume and have not progressed, the response has been for an average of 11 months. The follow-up for two tumors that remained unchanged was 10 and 34 months (average 22 months). A third tumor was unchanged at 42 months but the patient died of new disease adjacent to the treated area in the anterior skull base. There were no complications and the quality of life following the procedure was maintained or improved in every case. Gamma surgery is effective in palliating the patients by decreasing tumor volume and delaying recurrence.     

Evaluation of a successful intervention for sustainability and effects in post research phase.

INTRODUCTION: Promoting appropriate use of drugs is an essential element in achieving quality of health and medical cares for patients and the community, and also to minimize financial burden. OBJECTIVE: The objective of this paper is to assess the successful intervention for sustainability and effects in post research phase. To address these problems, a variety of educational, managerial and regulatory strategies to improve prescribing have been tried in Nepal. When training is combined with a managerial intervention i.e. peer-group discussion, it results into improved changes in prescribing practices of paramedics in several practices. METHODOLOGY: A prospective, three-way design study consisting of small group training, small group training followed by peer-group discussion and control was conducted in three regions of Nepal including one hill and two terai (plains) districts from each region. The study included all health post from the sampled districts, making 80 health posts the study population. RESULTS: The study revealed the effectiveness of the peer-group discussion approach in improving the prescribing practices. An assessment to identify the sustainability of the strategy and its effect within the district healthcare system after the completion of the research phase was undertaken. The study found that peer-group discussion was discontinued in all targeted districts and the improved practices were not sustained after the completion of the research. Various reasons have been found for not continuing the effective intervention.     

Recognition and unfolding of human telomeric G-quadruplex by short peptide binding identified from the HRDC domain of BLM helicase

Research in recent decades has revealed that the guanine (G)-quadruplex secondary structure in DNA modulates a variety of cellular events that are mostly related to serious diseases. Systems capable of regulating DNA G-quadruplex structures would therefore be useful for the modulation of various cellular events to produce biological effects. A high specificity for recognition of telomeric G-quadruplex has been observed for BLM helicase. We identified peptides from the HRDC domain of BLM using a molecular docking approach with various available solutions and crystal structures of human telomeres and recently created a peptide library. Herein, we tested one peptide (BLM HRDC peptide) from the library and examined its interaction with human telomeric variant-1 (HTPu-var-1) to understand the basis of G4-protein interactions. Our circular dichroism (CD) data showed that HTPu-var-1 folded into an anti-parallel G-quadruplex, and the CD intensity significantly decreased upon increasing the peptide concentration. There was a significant decrease in hypochromicity due to the formation of G-quadruplex-peptide complex at 295 nm, which indicated the unfolding of structure due to the decrease in stacking interactions. The fluorescence data showed quenching upon titrating the peptide with HTPu-var-1-G4. Electrophoretic mobility shift assay confirmed the unfolding of the G4 structure. Cell viability was significantly reduced in the presence of the BLM peptide, with IC₅₀ values of 10.71 μM and 11.83 μM after 72 and 96 hours, respectively. These results confirmed that the selected peptide has the ability to bind to human telomeric G-quadruplex and unfold it. This is the first report in which a peptide was identified from the HRDC domain of the BLM G4-binding protein for the exploration of the G4-binding motif, which suggests a novel strategy to target G4 using natural key peptide segments.

Schematic representation of (HTPu–var-1-G4) located at the 3′ end, formation of G-quadruplex, model of the G-quadruplex structure, base stacking between G-quadruplex planes, G-quadruplex structure-peptide complex and twisting of G-quadruplex planes upon peptide binding.     

Burkholderia pseudomallei in Environment of Adolescent Siblings with Melioidosis,Kerala, India, 2019

In 2019, Burkholderia pseudomallei was isolated from the backyard of 2 siblings with melioidosis in Kerala, India. This finding highlights the value of healthcare providers being aware of risk for melioidosis in febrile patients, of residents taking precautions when outside, and of increasing environmental surveillance for B. pseudomallei in this region.