Publications by authors named "N Narasimha Murthy"

532 Publications

Chiari malformation type 1 presenting as isolated unilateral foot drop with rapid recovery following posterior fossa decompression.

Childs Nerv Syst 2021 Jul 7. Epub 2021 Jul 7.

Department of Neurological Surgery, Northwestern University, Chicago, IL, USA.

Background: Chiari malformation (CM) type 1 is characterized by descent of the cerebellar tonsils resulting from crowding of the posterior fossa. In 30% of cases, it is associated with syringomyelia. When symptomatic, it may result in a classic constellation of symptoms.

Case Presentation: Here we describe a case of a 16-year-old male who presented with isolated, unilateral foot drop due to CM type 1 and holosyrinx. This unique presentation is extremely rare, and we additionally present a review of all other reported cases in the literature. After undergoing posterior fossa decompression with C1 laminectomy and duraplasty, our patient made a complete neurological recovery within 2 weeks postoperatively and his MRI entire spine at 3 months postoperatively demonstrated a nearly complete resolution of the holosyrinx with significant decompression of the foramen magnum.

Conclusion: This rare presentation highlights the importance of maintaining a broad differential, particularly in pediatric patients, and expediting the workup in order to offer a surgical decompression within 1-2 months of foot weakness to maximize the probability of a full neurological recovery.
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http://dx.doi.org/10.1007/s00381-021-05275-9DOI Listing
July 2021

Screening a Library of FDA-Approved and Bioactive Compounds for Antiviral Activity against SARS-CoV-2.

ACS Infect Dis 2021 Jun 15. Epub 2021 Jun 15.

School of Public Health, Division of Infectious Diseases and Vaccinology, University of California, Berkeley, Berkeley, California 94720, United States.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has emerged as a major global health threat. The COVID-19 pandemic has resulted in over 168 million cases and 3.4 million deaths to date, while the number of cases continues to rise. With limited therapeutic options, the identification of safe and effective therapeutics is urgently needed. The repurposing of known clinical compounds holds the potential for rapid identification of drugs effective against SARS-CoV-2. Here, we utilized a library of FDA-approved and well-studied preclinical and clinical compounds to screen for antivirals against SARS-CoV-2 in human pulmonary epithelial cells. We identified 13 compounds that exhibit potent antiviral activity across multiple orthogonal assays. Hits include known antivirals, compounds with anti-inflammatory activity, and compounds targeting host pathways such as kinases and proteases critical for SARS-CoV-2 replication. We identified seven compounds not previously reported to have activity against SARS-CoV-2, including B02, a human RAD51 inhibitor. We further demonstrated that B02 exhibits synergy with remdesivir, the only antiviral approved by the FDA to treat COVID-19, highlighting the potential for combination therapy. Taken together, our comparative compound screening strategy highlights the potential of drug repurposing screens to identify novel starting points for development of effective antiviral mono- or combination therapies to treat COVID-19.
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http://dx.doi.org/10.1021/acsinfecdis.1c00017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231672PMC
June 2021

A traceless linker for aliphatic amines that rapidly and quantitatively fragments after reduction.

Chem Sci 2020 Aug 12;11(33):8973-8980. Epub 2020 Aug 12.

Department of Bioengineering, University of California Berkeley University Avenue Berkeley CA 94720 USA

Reduction sensitive linkers (RSLs) have the potential to transform the field of drug delivery due to their ease of use and selective cleavage in intracellular environments. However, despite their compelling attributes, developing reduction sensitive self-immolative linkers for aliphatic amines has been challenging due to their poor leaving group ability and high p values. Here a traceless self-immolative linker composed of a dithiol-ethyl carbonate connected to a benzyl carbamate (DEC) is presented, which can modify aliphatic amines and release them rapidly and quantitatively after disulfide reduction. DEC was able to reversibly modify the lysine residues on CRISPR-Cas9 with either PEG, the cell penetrating peptide Arg, or donor DNA, and generated Cas9 conjugates with significantly improved biological properties. In particular, Cas9-DEC-PEG was able to diffuse through brain tissue significantly better than unmodified Cas9, making it a more suitable candidate for genome editing in animals. Furthermore, conjugation of Arg to Cas9 with DEC was able to generate a self-delivering Cas9 RNP that could edit cells without transfection reagents. Finally, conjugation of donor DNA to Cas9 with DEC increased the homology directed DNA repair (HDR) rate of the Cas9 RNP by 50% in HEK 293T cell line. We anticipate that DEC will have numerous applications in biotechnology, given the ubiquitous presence of aliphatic amines on small molecule and protein therapeutics.
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http://dx.doi.org/10.1039/d0sc00929fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163433PMC
August 2020

Quality of life (QOL) among older persons in an urban and rural area of Bangalore, South India.

J Family Med Prim Care 2021 Jan 30;10(1):272-277. Epub 2021 Jan 30.

Department of Community Medicine, MS Ramaiah Medical College, Bangalore, Karnataka, India.

Introduction: The increasing ageing population of India has unique challenges due to changing social structure, health issues and inaccessible healthcare facilities. These challenges can adversely affect the quality of life (QOL) of older persons. Hence, this study was undertaken with the objective of assessing the QOL among older persons in an urban and rural area of Bangalore.

Materials And Methods: Cross-sectional study was done among 977 older persons 60 years and above. Census enumeration blocks in urban areas and villages in rural areas were randomly selected and all older persons meeting the inclusion criteria were administered the WHOQOL-Bref questionnaire.

Results: Mean QOL scores (SD) in the physical, psychological, social relationship and environmental domains were 50.5 (5.5), 49.2 (5.5), 49.4 (6.5) and 49.3 (5.1) in rural areas and 57.4 (8.9), 58.6 (8.8), 64.6 (10.8) and 60.0 (9.4) in urban areas, respectively. Compared to urban, rural older persons uniformly have lower QOL irrespective of sex, education or financial dependence.

Conclusion: Inequitable health resource distribution and inadequate social support systems must be addressed to improve the QOL of older persons, especially in rural areas. Primary care providing essential services can bridge this urban-rural divide and improve QOL of older persons.
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http://dx.doi.org/10.4103/jfmpc.jfmpc_1241_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132806PMC
January 2021

Disparities in COVID-19 Vaccination Coverage Between Urban and Rural Counties - United States, December 14, 2020-April 10, 2021.

MMWR Morb Mortal Wkly Rep 2021 May 21;70(20):759-764. Epub 2021 May 21.

Approximately 60 million persons in the United States live in rural counties, representing almost one fifth (19.3%) of the population.* In September 2020, COVID-19 incidence (cases per 100,000 population) in rural counties surpassed that in urban counties (1). Rural communities often have a higher proportion of residents who lack health insurance, live with comorbidities or disabilities, are aged ≥65 years, and have limited access to health care facilities with intensive care capabilities, which places these residents at increased risk for COVID-19-associated morbidity and mortality (2,3). To better understand COVID-19 vaccination disparities across the urban-rural continuum, CDC analyzed county-level vaccine administration data among adults aged ≥18 years who received their first dose of either the Pfizer-BioNTech or Moderna COVID-19 vaccine, or a single dose of the Janssen COVID-19 vaccine (Johnson & Johnson) during December 14, 2020-April 10, 2021 in 50 U.S. jurisdictions (49 states and the District of Columbia [DC]). Adult COVID-19 vaccination coverage was lower in rural counties (38.9%) than in urban counties (45.7%) overall and among adults aged 18-64 years (29.1% rural, 37.7% urban), those aged ≥65 years (67.6% rural, 76.1% urban), women (41.7% rural, 48.4% urban), and men (35.3% rural, 41.9% urban). Vaccination coverage varied among jurisdictions: 36 jurisdictions had higher coverage in urban counties, five had higher coverage in rural counties, and five had similar coverage (i.e., within 1%) in urban and rural counties; in four jurisdictions with no rural counties, the urban-rural comparison could not be assessed. A larger proportion of persons in the most rural counties (14.6%) traveled for vaccination to nonadjacent counties (i.e., farther from their county of residence) compared with persons in the most urban counties (10.3%). As availability of COVID-19 vaccines expands, public health practitioners should continue collaborating with health care providers, pharmacies, employers, faith leaders, and other community partners to identify and address barriers to COVID-19 vaccination in rural areas (2).
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http://dx.doi.org/10.15585/mmwr.mm7020e3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136424PMC
May 2021
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