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1.
J Drugs Dermatol ; 22(11): e4-e8, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37943266

ABSTRACT

The COVID-19 pandemic has sparked an increase in focus and use of telemedicine in several patient care settings. This survey study was distributed to actively practicing US-based physicians and examines telehealth use 2 years after the beginning of the COVID pandemic from a physician’s perspective. Notable findings include telehealth benefits which include increased patient access and the ability to work from home. A continued drawback in telehealth visits is the limitations on a complete physical examination, a drawback that was emphasized by the dermatology community. While this study sheds light on the developing nature of telehealth, it is limited by its retrospective nature and sample size. Future research with larger sample sizes focusing on economic incentives and telemedicine training may help to overcome barriers to using telehealth.  J Drugs Dermatol. 2023;22(11):e4-e8    doi:10.36849/JDD.7386e.


Subject(s)
Physicians , Telemedicine , Humans , Pandemics , Retrospective Studies , Perception
5.
Elife ; 82019 03 12.
Article in English | MEDLINE | ID: mdl-30860482

ABSTRACT

Renal medullary carcinoma (RMC) is a rare and deadly kidney cancer in patients of African descent with sickle cell trait. We have developed faithful patient-derived RMC models and using whole-genome sequencing, we identified loss-of-function intronic fusion events in one SMARCB1 allele with concurrent loss of the other allele. Biochemical and functional characterization of these models revealed that RMC requires the loss of SMARCB1 for survival. Through integration of RNAi and CRISPR-Cas9 loss-of-function genetic screens and a small-molecule screen, we found that the ubiquitin-proteasome system (UPS) was essential in RMC. Inhibition of the UPS caused a G2/M arrest due to constitutive accumulation of cyclin B1. These observations extend across cancers that harbor SMARCB1 loss, which also require expression of the E2 ubiquitin-conjugating enzyme, UBE2C. Our studies identify a synthetic lethal relationship between SMARCB1-deficient cancers and reliance on the UPS which provides the foundation for a mechanism-informed clinical trial with proteasome inhibitors.


Subject(s)
Carcinoma, Medullary/genetics , Kidney Neoplasms/genetics , Proteasome Endopeptidase Complex/genetics , Proteasome Inhibitors/pharmacology , SMARCB1 Protein/genetics , Alleles , Animals , CRISPR-Cas Systems , Carcinoma, Medullary/drug therapy , Cell Cycle , Cell Line, Tumor , Exome , Female , Humans , In Situ Hybridization, Fluorescence , Kidney/metabolism , Kidney Neoplasms/drug therapy , Mice , Mice, Nude , Mutation , Neoplasm Transplantation , RNA Interference , Sequence Analysis, RNA , Ubiquitin/chemistry , Whole Genome Sequencing
6.
Curr Opin HIV AIDS ; 10(3): 198-206, 2015 May.
Article in English | MEDLINE | ID: mdl-25700203

ABSTRACT

PURPOSE OF REVIEW: Infection of long-lived CD4 T cells is a major obstacle to HIV remission, and antiretroviral therapy (ART) instituted during acute HIV infection restricts HIV reservoir establishment. Broadly neutralizing antibodies (bNAbs) may be employed in conjunction with early ART as strategies toward HIV remission. RECENT FINDINGS: Proof-of-concept studies in vitro and in animal models demonstrated bNAbs' ability to block viral entry into cells, suppress viremia and reduce cell-associated viral DNA. Combination bNAbs were more effective than single bNAb in suppressing viremia. When bNAb was used with ART with or without combination latency reversing agents, it prevented viral rebound after ART interruption in at least half of the animals. In one study, macaques with low baseline viral load achieved viral remission even after the blood bNAb titer was no longer detected. SUMMARY: The acute HIV infection period represents a unique opportunity to explore the use of bNAbs with ART to limit the reservoir seeding that may enhance the chance of HIV remission. This article discusses the effects of early ART and bNAbs on HIV reservoirs and proposes research strategies in acute HIV infection aiming at HIV reservoir reduction and HIV remission.


Subject(s)
Antibodies, Neutralizing/immunology , HIV Antibodies/immunology , HIV Infections , HIV-1/immunology , Animals , Anti-Retroviral Agents , CD4-Positive T-Lymphocytes , HIV Infections/immunology , HIV Infections/virology , Humans , Mice
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