ABSTRACT
Male infertility caused by genetic mutations is an important type of infertility. Currently, there is no reliable method in the clinic to address this medical need. The emergence of mRNA therapy provides a possible strategy for restoring mutant genes in the reproductive system. However, effective delivery of mRNA to spermatocytes remains a formidable challenge. Here a series of cholesterol-amino-phosphate (CAP) lipids are reported by integrating three bioactive moieties into a geometric structure, which is favorable for mRNA delivery. The results demonstrate that CAP-derived lipid nanoparticles (CAP LNPs) can deliver RNA including traditional mRNA and self-amplifying RNA (saRNA) encoding DNA Meiotic Recombinase 1 (Dmc1) protein in spermatocytes and treat male infertility caused by the Dmc1 gene mutation. Notably, the delivery efficiency of CAP LNPs is significantly higher than that of the MC3 and ALC-0315 LNPs, which is consistent with the design of CAP molecules. More importantly, a single injection of CAP LNPs-saRNA can produce Dmc1 protein for an extended period, which restores the spermatogenesis in the Dmc1 gene knockout mouse model. Overall, this study proves the concept of LNPs for the delivery of mRNA to spermatocytes, which provides a unique method to probe male infertility caused by the genetic mutation.
Subject(s)
Infertility, Male , RNA , Humans , Mice , Male , Animals , Spermatogenesis/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Infertility, Male/genetics , Infertility, Male/therapy , CholesterolABSTRACT
Complications of acute rhinosinusitis(ARS) in the pediatric population can include intra- and extracranial involvement from spread of infection. Though these infections are most commonly preceded by a URI, infection with Sars-CoV-2 (COVID-19) as the inciting event for complicated ARS has rarely been described in the pediatric population. Furthermore, decision making surrounding surgical management of acutely infected patients with COVID-19 remains complicated. This case demonstrates complicated ARS in an otherwise healthy 10-year-old patient with an orbital abscess following COVID-19 infection, ultimately requiring both internal and external surgical approaches for adequate management.
ABSTRACT
OBJECTIVES: People detained in correctional facilities are at high risk for infection with severe acute respiratory syndrome coronavirus 2, the virus that causes coronavirus disease 2019 (COVID-19). We described the epidemiology of the COVID-19 outbreak in a large urban jail system, including signs and symptoms at time of testing and risk factors for hospitalization. METHODS: This retrospective observational cohort study included all patients aged ≥18 years who were tested for COVID-19 during March 11-April 28, 2020, while in custody in the New York City jail system (N = 978). We described demographic characteristics and signs and symptoms at the time of testing and performed Cox regression analysis to identify factors associated with hospitalization among those with a positive test result. RESULTS: Of 978 people tested for COVID-19, 568 received a positive test result. Among symptomatic patients, the most common symptoms among those who received a positive test result were cough (n = 293 of 510, 57%) and objective fever (n = 288 of 510, 56%). Of 257 asymptomatic patients who were tested, 58 (23%) received a positive test result. Forty-five (8%) people who received a positive test result were hospitalized for COVID-19. Older age (aged ≥55 vs 18-34) (adjusted hazard ratio [aHR] = 13.41; 95% CI, 3.80-47.33) and diabetes mellitus (aHR = 1.99; 95% CI, 1.00-3.95) were significantly associated with hospitalization. CONCLUSIONS: A substantial proportion of people tested in New York City jails received a positive test result for COVID-19, including a large proportion of people tested while asymptomatic. During periods of ongoing transmission, asymptomatic screening should complement symptom-driven COVID-19 testing in correctional facilities. Older patients and people with diabetes mellitus should be closely monitored after COVID-19 diagnosis because of their increased risk for hospitalization.