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Michael R Duff, Jose M Borreguero, Matthew Cuneo, Arvind Ramanathan, Junhong He, Ganesh Kamath, Chakra S Chennubhotla, Flora Meilleur, Elizabeth E Howell, Kenneth W Herwig, Dean A A Myles, Pratul K Agarwal
Optimal enzyme activity depends on a number of factors, including structure and dynamics. The role of enzyme structure is well recognized, however, the linkage between protein dynamics and enzyme activity has given rise to a contentious debate. We have developed an approach that uses an aqueous mixture of organic solvent to control the functionally relevant enzyme dynamics (without changing the structure), which in turn modulates the enzyme activity. Using this approach, we predicted that the hydride transfer reaction catalyzed by the enzyme dihydrofolate reductase (DHFR) from Escherichia coli in aqueous mixtures of isopropanol (IPA) with water will decrease by ~3 fold at 20% (v/v) IPA concentration...
June 14, 2018: Biochemistry
Xing-Wang Zhu, Yuan Shi, Li-Ping Shi, Ling Liu, Jiang Xue, Rangasamy Ramanathan
BACKGROUND: Invasive mechanical ventilation (IMV) is associated with the development of adverse pulmonary and non-pulmonary outcomes in very premature infants. Various modes of non-invasive respiratory support are increasingly being used to decrease the incidence of bronchopulmonary dysplasia. The aim of this trial is to compare the effect of non-invasive high-frequency oscillatory ventilation (NHFOV) and nasal continuous positive airway pressure (NCPAP) in preterm infants with respiratory distress syndrome (RDS) as a primary non-invasive ventilation support mode...
June 14, 2018: Trials
Arunachalam Kannappan, Ramar Mohankumar, Ramanathan Srinivasan, Govindaraju Archunan, Shunmugiah Karutha Pandian, Kandasamy Ruckmani, Arumugam Veera Ravi
Staphylococcal infections associated with indwelling medical devices are difficult to eradicate owing to its recalcitrant nature of biofilms to conventional antibiotics. In our earlier study, we reported the efficacy of geraniol (GE) in inhibiting the in vitro biofilm formation of S. epidermidis and adaptive resistant development. To examine the in vivo potential of GE in eradicating the in vivo colonization of S. epidermidis, an implanted rat jugular vein catheter model was developed. Oral supplementation of GE (GE at 200 mg/kg bw for three days) in rats infected with S...
June 11, 2018: Pathogens and Disease
Daniel H Ahn, Ramesh K Ramanathan, Tanios Bekaii-Saab
Pancreatic adenocarcinoma is typically refractory to conventional treatments and associated with poor prognosis. While therapeutic advances over the past several years have improved patient outcomes, the observed benefits have been modest at best, highlighting the need for continued development of alternate treatment strategies. The tumor microenvironment has been identified as being integral to oncogenesis through its direct effect on cellular pathway communication, immune inhibition, and promoting chemo-resistance...
June 11, 2018: Cancers
Sandra Y Lin, Antoine Azar, Catalina Suarez-Cuervo, Gregory B Diette, Emily Brigham, Jessica Rice, Murugappan Ramanathan, Karen A Robinson
BACKGROUND: The purpose of the systematic review is to evaluate the efficacy and safety of sublingual immunotherapy (SLIT) for the treatment of allergic asthma. METHODS: PubMed, Embase, and CENTRAL databases were searched, updating an earlier review (January 1, 2005 through May 8, 2017). Randomized, controlled studies (RCTs) were included, which reported one of the prespecified outcomes: asthma symptoms measured by control composite scores; quality of life; medication use; pulmonary physiology; and health-care utilization...
June 9, 2018: International Forum of Allergy & Rhinology
Murugesan Sivaranjani, Ramanathan Srinivasan, Chairmandurai Aravindraja, Shunmugiah Karutha Pandian, Arumugam Veera Ravi
The present study was designed to investigate the anti-biofilm potential of alpha-mangostin (α-MG) against Acinetobacter baumannii (AB). The biofilm inhibitory concentration (BIC) of α-MG against AB was found to be 2 μg ml-1 . α-MG (0.5, 1 and 2 μg ml-1 ) exhibited non-bactericidal concentration-dependent anti-biofilm activities against AB. However, α-MG failed to disintegrate the mature biofilms of AB even at a 10-fold increased concentration from its BIC. Results from qRT-PCR and in vitro bioassays further demonstrated that α-MG downregulated the expression of bfmR, pgaA, pgaC, csuA/B, ompA, bap, katE, and sodB genes, which correspondingly affects biofilm formation and its associated virulence traits...
June 5, 2018: Biofouling
Geng Zhou, Ming Hua Li, Gabriel Tudor, Hai Tao Lu, Ramanathan Kadirvel, David Kallmes
Cerebral ischemia and stroke are increasing in prevalence and are among the leading causes of morbidity and mortality in both developed and developing countries. Despite the progress in endovascular treatment, ischemia/reperfusion (IR) injury is an important contributor to post-surgical mortality and morbidity affecting a wide range of neurointerventional procedures. However, pharmacological recruitment of effective cerebral protective signaling has been largely disappointing to date. In remote ischemic conditioning (RIC), repetitive transient mechanical obstruction of vessels at a limb remote from the IR injury site protects vital organs from IR injury and confers infarction size reduction following prolonged arterial occlusion...
2018: Frontiers in Neurology
Jodie Bailie, Frances Clare Cunningham, Roxanne Gwendalyn Bainbridge, Megan E Passey, Alison Frances Laycock, Ross Stewart Bailie, Sarah L Larkins, Jenny S M Brands, Shanthi Ramanathan, Seye Abimbola, David Peiris
Efforts to strengthen health systems require the engagement of diverse, multidisciplinary stakeholder networks. Networks provide a forum for experimentation and knowledge creation, information exchange and the spread of good ideas and practice. They might be useful in addressing complex issues or 'wicked' problems, the solutions to which go beyond the control and scope of any one agency. Innovation platforms are proposed as a novel type of network because of their diverse stakeholder composition and focus on problem solving within complex systems...
2018: BMJ Global Health
Bijay Kumar Behera, Abhishek Das, Dhruba Jyoti Sarkar, Pabudi Weerathunge, Pranaya Kumar Parida, Basanta Kumar Das, Palanisami Thavamani, Rajesh Ramanathan, Vipul Bansal
Polycyclic Aromatic Hydrocarbons (PAHs) are among the most ubiquitous environmental pollutants of high global concern. PAHs belong to a diverse family of hydrocarbons with over one hundred compounds known, each containing at least two aromatic rings in their structure. Due to hydrophobic nature, PAHs tend to accumulate in the aquatic sediments, leading to bioaccumulation and elevated concentrations over time. In addition to their well-manifested mutagenic and carcinogenic effects in humans, they pose severe detrimental effects to aquatic life...
May 25, 2018: Environmental Pollution
Asim Rizvi, Seyed Mohammad Seyedsaadat, Mohammad Hassan Murad, Waleed Brinjikji, Sean T Fitzgerald, Ramanathan Kadirvel, Alejandro A Rabinstein, David F Kallmes
BACKGROUND: Conventionally, 'successful' endovascular thrombectomy (EVT) had been defined as achieving revascularization of thrombolysis in cerebral infarction (TICI)-2B or greater, rather than as 'complete' (TICI-3) versus 'incomplete' (TICI-2B) revascularization. PURPOSE: We performed a systematic review and meta-analysis of studies comparing clinical outcomes between patients with TICI-2B and TICI-3 revascularization. METHODS: Multiple databases were searched for relevant publications between January 2003 and March 2018...
May 25, 2018: Journal of Neurointerventional Surgery
Jian Y Cheng, Andrew Martin, Ganesh Ramanathan, Bruce A Cooper
Background: Screening potential live kidney donors is an intense process for both candidates and the healthcare system. It is conventionally implemented using a standard generic protocol. Efficiencies in this process could potentially be achieved using personalized protocols that are optimized for a given candidate. Aim: To create personalized protocols (by age, sex, and paired exchange status) and evaluate them relative to the standard generic protocol. Methods: Two personalized protocols were created...
May 2018: Transplantation Direct
Kiran Kumar Solingapuram Sai, Jaya Prabhakaran, Gayathri Ramanathan, Stephanie Rideout, Christopher Whitlow, Akiva Mintz, J John Mann, J S Dileep Kumar
Microtubules (MTs) are highly abundant throughout the cytoskeleton, and their dysfunction is implicated in the pathogenesis of malignancies, various neurodegenerative disorders, and brain injuries. Validated radiotracers reported so far for MTs are [11 C]paclitaxel, [18 F]fluoropaclitaxel, and [11 C]docetaxel; however, they are well-characterized substrates of efflux transporters and consequently have poor uptake into the brain due to minimal blood brain barrier (BBB) penetration. PET imaging of MT expression requires radiolabeled BBB penetrating MT ligands, and it may offer a direct and more sensitive approach for early diagnosis, monitoring disease progression, and treatment effects in brain diseases and assessing the clinical potential of targeted therapeutics and treatments...
May 10, 2018: ACS Medicinal Chemistry Letters
Thomas A Chavez, Ashwini Lakshmanan, Lizzette Figueroa, Narayan Iyer, Theodora A Stavroudis, Arlene Garingo, Philippe S Friedlich, Rangasamy Ramanathan
OBJECTIVES: To describe the frequency of non-invasive ventilation (NIV) and endotracheal intubation use in neonates diagnosed with respiratory distress syndrome (RDS); to describe resources utilization (length of stay (LOS), charges, costs) among NIV and intubated RDS groups. STUDY DESIGN: Retrospective study from the national Kid's Inpatient Database of the Healthcare Cost and Utilization Project, for the years 1997-2012. Propensity scoring and multivariate regression analysis used to describe differences...
May 24, 2018: Journal of Perinatology: Official Journal of the California Perinatal Association
Davendra P S Sohal, Erin B Kennedy, Alok Khorana, Mehmet S Copur, Christopher H Crane, Ignacio Garrido-Laguna, Smitha Krishnamurthi, Cassadie Moravek, Eileen M O'Reilly, Philip A Philip, Ramesh K Ramanathan, Joseph T Ruggiero, Manish A Shah, Susan Urba, Hope E Uronis, Michelle W Lau, Daniel Laheru
Purpose In 2016, ASCO published a guideline to assist in clinical decision making in metastatic pancreatic cancer for initial assessment after diagnosis, first- and second-line treatment options, palliative and supportive care, and follow-up. The purpose of this update is to incorporate new evidence related to second-line therapy for patients who have experienced disease progression or intolerable toxicity during first-line therapy. Methods ASCO convened an Expert Panel to conduct a systematic review of the literature on second-line therapy published between June 2015 and January 2018...
May 23, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Akash Srivaths, Shyam Ramanathan, Seethalakshmi Sakthivel, Skm Habeeb
Apoptosis Inducing Factor protein has a dual role depending on its localization in mitochondrion (energy production) and nucleus (induces apoptosis). Cell damage transports this protein to nucleus which otherwise favors mitochondrion. The alteration of Nuclear Localisation Signal tags could aid nuclear translocation. In this study, apoptosis inducing factor protein (AIF) was conjugated with strong NLS tags and its binding affinity with Importin was studied using in silico approaches such as molecular modeling and docking...
2018: Bioinformation
R Ramanathan, E A Voigt, R B Kennedy, G A Poland
Mumps, a common childhood disease in the pre-vaccine era that causes swelling of the parotid salivary glands, can lead to orchitis, viral meningitis, and sensorineural deafness. While the incidence of disease decreased dramatically after the vaccine was added to standard vaccination schedules, the disease has made a substantial resurgence in recent years. As a result, it becomes critical to examine the factors involved in recurring outbreaks. Although low and incomplete vaccination coverage may be a key reason, it does not fully explain the issue due to the high rate of occurrence in populations with high vaccination coverage rates...
May 18, 2018: Vaccine
Rong Zhang, Rui-Wena Huang, Xi-Ronga Gao, Xiao-Minga Peng, Li-Hui Zhu, Ramanathan Rangasamy, Jos M Latour
OBJECTIVES: To evaluate the effectiveness and safety of a family-centered care intervention in a Chinese neonatal ICU. DESIGN: Pilot study using a randomized controlled trial design to inform a main randomized controlled trial study. SETTING: Stand-alone tertiary children's hospital in China with a 60-bed neonatal ICU serving as a regional neonatal ICU center. PATIENTS: Premature infants (n = 61) and their parents (n = 110)...
May 17, 2018: Pediatric Critical Care Medicine
Aparna Ramanathan, Melody J Eckardt, Brett D Nelson, Moytrayee Guha, Monica Oguttu, Zaid Altawil, Thomas Burke
BACKGROUND: Postpartum hemorrhage is the leading cause of maternal mortality in low- and middle-income countries. While evidence on uterine balloon tamponade efficacy for severe hemorrhage is encouraging, little is known about safety of this intervention. The objective of this study was to evaluate the safety of an ultra-low-cost uterine balloon tamponade package (named ESM-UBT) for facility-based management of uncontrolled postpartum hemorrhage (PPH) in Kenya and Sierra Leone. METHODS: Data were collected on complications/adverse events in all women who had an ESM-UBT device placed among 92 facilities in Sierra Leone and Kenya, between September 2012 and December 2015, as part of a multi-country study...
May 15, 2018: BMC Pregnancy and Childbirth
Karen McPhail-Bell, Veronica Matthews, Roxanne Bainbridge, Michelle Louise Redman-MacLaren, Deborah Askew, Shanthi Ramanathan, Jodie Bailie, Ross Bailie
In Australia, Indigenous people experience poor access to health care and the highest rates of morbidity and mortality of any population group. Despite modest improvements in recent years, concerns remains that Indigenous people have been over-researched without corresponding health improvements. Embedding Indigenous leadership, participation, and priorities in health research is an essential strategy for meaningful change for Indigenous people. To centralize Indigenous perspectives in research processes, a transformative shift away from traditional approaches that have benefited researchers and non-Indigenous agendas is required...
2018: Frontiers in Public Health
Emmanouil S Brilakis, Robert Edson, Deepak L Bhatt, Steven Goldman, David R Holmes, Sunil V Rao, Kendrick Shunk, Bavana V Rangan, Kreton Mavromatis, Kodangudi Ramanathan, Anthony A Bavry, Santiago Garcia, Faisal Latif, Ehrin Armstrong, Hani Jneid, Todd A Conner, Todd Wagner, Judit Karacsonyi, Lauren Uyeda, Beverly Ventura, Aaron Alsleben, Ying Lu, Mei-Chiung Shih, Subhash Banerjee
BACKGROUND: Few studies have examined the efficacy of drug-eluting stents (DES) for reducing aortocoronary saphenous vein bypass graft (SVG) failure compared with bare-metal stents (BMS) in patients undergoing stenting of de-novo SVG lesions. We assessed the risks and benefits of the use of DES versus BMS in de-novo SVG lesions. METHODS: Patients were recruited to our double-blind, randomised controlled trial from 25 US Department of Veterans Affairs centres. Eligible participants were aged at least 18 years and had at least one significant de-novo SVG lesion (50-99% stenosis of a 2·25-4·5 mm diameter SVG) requiring percutaneous coronary intervention with intent to use embolic protection devices...
May 19, 2018: Lancet
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