Ventricular Septal Rupture in a 4-Year-Old Child Following Blunt Chest Injury

We report on a 4-year-old child who developed rupture of the ventricular septum after a blunt chest injury. The symptoms appeared more than 12 h later with progressive deterioration in his hemodynamic status. The diagnosis was made by echocardiography and the large defect in the muscular part of the ventricular septum was successfully closed at surgery.     

Pigmented epiretinal membranes caused by RPE migration: OCT-based observational case reports

Epiretinal membranes are cellular sheets on the retinal surface that are formed due to varied etiologies. We present two observational case reports to demonstrate the transretinal migration of the retinal pigment epithelium in pigmented idiopathic epiretinal membranes using optical coherence tomography.     

Paxillin is a target for somatic mutations in lung cancer: implications for cell growth and invasion

Lung cancer is characterized by abnormal cell growth and invasion, and the actin cytoskeleton plays a major role in these processes. The focal adhesion protein paxillin is a target of a number of oncogenes involved in key signal transduction and important in cell motility and migration. In lung cancer tissues, we have found that paxillin was highly expressed (compared with normal lung), amplified (12.1%, 8 of 66) and correlated with increased MET and epidermal growth factor receptor (EGFR) gene copy numbers, or mutated (somatic mutation rate of 9.4%, 18 of 191). Paxillin mutations (19 of 21) were clustered between LD motifs 1 and 2 and the LIM domains. The most frequent point mutation (A127T) enhanced lung cancer cell growth, colony formation, focal adhesion formation, and colocalized with Bcl-2 in vitro. Gene silencing from RNA interference of mutant paxillin led to reduction of cell viability. A murine in vivo xenograft model of A127T paxillin showed an increase in tumor growth, cell proliferation, and invasion. These results establish an important role for paxillin in lung cancer.     

Molecular imaging of the efficacy of heat shock protein 90 inhibitors in living subjects

Heat shock protein 90 alpha (Hsp90 alpha)/p23 and Hsp90 beta/p23 interactions are crucial for proper folding of proteins involved in cancer and neurodegenerative diseases. Small molecule Hsp90 inhibitors block Hsp90 alpha/p23 and Hsp90 beta/p23 interactions in part by preventing ATP binding to Hsp90. The importance of isoform-selective Hsp90 alpha/p23 and Hsp90 beta/p23 interactions in determining the sensitivity to Hsp90 was examined using 293T human kidney cancer cells stably expressing split Renilla luciferase (RL) reporters. Interactions between Hsp90 alpha/p23 and Hsp90 beta/p23 in the split RL reporters led to complementation of RL activity, which was determined by bioluminescence imaging of intact cells in cell culture and living mice using a cooled charge-coupled device camera. The three geldanamycin-based and seven purine-scaffold Hsp90 inhibitors led to different levels of inhibition of complemented RL activities (10-70%). However, there was no isoform selectivity to both classes of Hsp90 inhibitors in cell culture conditions. The most potent Hsp90 inhibitor, PU-H71, however, led to a 60% and 30% decrease in RL activity (14 hr) in 293T xenografts expressing Hsp90 alpha/p23 and Hsp90 beta/p23 split reporters respectively, relative to carrier control-treated mice. Molecular imaging of isoform-specific Hsp90 alpha/p23 and Hsp90 beta/p23 interactions and efficacy of different classes of Hsp90 inhibitors in living subjects have been achieved with a novel genetically encoded reporter gene strategy that should help in accelerating development of potent and isoform-selective Hsp90 inhibitors.     

Retinal detachment in eyes treated with Aurolab aqueous drainage implant for refractory glaucoma - Incidence and outcomes

Purpose:To analyze the incidence of rhegmatogenous retinal detachment (RRD) in patients who have undergone prior Aurolab aqueous drainage implant (AADI) surgery and report outcomes in terms of anatomic, visual acuity, and intraocular pressure (IOP) findings.Methods:Case records of all patients who underwent RRD repair after AADI surgery from 2013 to 2019 were retrospectively analyzed. Data collected included patient demographics, ocular examination findings at all visits including IOP and best-corrected visual acuity (BCVA) and clinical findings related to RRD both at baseline and postoperatively.Results:Ten eyes of nine patients were included in study. The mean age of patients was 28.2 years (median: 15 years, range: 6–83 years). Mean duration between AADI and RRD was 14 months (median 2.5 months; range 2 days-72 months). All eyes underwent pars plana vitrectomy with silicon oil injection. The preoperative LogMAR BCVA (logarithm of the minimum angle of resolution) was 2.52 ± 0.15 which improved to 2.29 ± 0.58 at final follow-up; however, only one eye had vision ≥ 20/400 largely due to recurrent RRD and advanced glaucomatous disc damage. Postoperatively retina was attached in 6 eyes (60%) and IOP was ≤ 21 mmHg in 5 out of 6 eyes with anatomic successConclusion:The incidence of RRD following AADI was found to be 0.86% in our study. Pars plana vitrectomy (PPV) with silicon oil tamponade was the preferred approach in the management of these eyes with IOP being well controlled post PPV. However, visual acuity outcomes were largely unsatisfactory due to recurrent RRD and preexisting advanced glaucoma.     

Innate and Adaptive Immune Responses in the Upper Respiratory Tract and the Infectivity of SARS-CoV-2

Increasing evidence shows the nasal epithelium to be the initial site of SARS-CoV-2 infection, and that early and effective immune responses in the upper respiratory tract (URT) limit and eliminate the infection in the URT, thereby preventing infection of the lower respiratory tract and the development of severe COVID-19. SARS-CoV-2 interferes with innate immunity signaling and evolves mutants that can reduce antibody-mediated immunity in the URT. Recent genetic and immunological advances in understanding innate immunity to SARS-CoV-2 in the URT, and the ability of prior infections as well as currently available injectable and potential intranasal COVID-19 vaccines to generate anamnestic adaptive immunity in the URT, are reviewed. It is suggested that the more detailed investigation of URT immune responses to all types of COVID-19 vaccines, and the development of safe and effective COVID-19 vaccines for intranasal administration, are important needs.     

COVID-19 vaccine hesitancy linked to increased internet search queries for side effects on fertility potential in the initial rollout phase following Emergency Use Authorization

The Emergency Use Authorization (EUA) of the COVID-19 vaccine on December 11, 2020 has been met with hesitancy for uptake with some citing potential impacts on future fertility. We hypothesised that irrespective of sex, fertility-related queries would markedly increase during the 48 days following EUA of the coronavirus vaccine. We sought to objectively identify trends in internet search queries on public concerns regarding COVID-19 vaccine side effects on fertility that might impact vaccine uptake. We used Google Trends to investigate queries in Google's Search Engine relating to the coronavirus vaccine and fertility between 10/24/2020 and 1/27/2021. The five most queried terms were identified as: ‘COVID Vaccine Fertility’, ‘COVID Vaccine and Infertility’, ‘COVID Vaccine Infertility’, ‘COVID Vaccine Fertility CDC’, and ‘COVID 19 Vaccine Infertility’ with an increase of 710.47%, 207.56%, 264.35%, 2,943.7%, and 529.26%, respectively, all p < .001. This study indicates that there was an increase in online COVID-19 vaccine-related queries regarding fertility side effects coinciding with the Emergency Use Authorization (EUA) on December 11, 2020. Our results objectively evidence the increased concern regarding the vaccine and likely demonstrate a major cause for hesitancy in vaccine uptake. Future studies and counselling with patients should be undertaken to help mitigate these concerns.