A Short Series of Case Reports of COVID-19 in Immunocompromised Patients

Immunocompromised individuals are at risk of prolonged SARS-CoV-2 infection due to weaker immunity, co-morbidities, and lowered vaccine effectiveness, which may evolve highly mutated variants of SARS-CoV-2. Nonetheless, limited data are available on the immune responses elicited by SARS-CoV-2 infection, reinfections, and vaccinations with emerging variants in immunocompromised patients. We analyzed clinical samples that were opportunistically collected from eight immunocompromised individuals for mutations in SARS-CoV-2 genomes, neutralizing antibody (NAb) titers against different SARS-CoV-2 variants, and the identification of immunoreactive epitopes using a high-throughput coronavirus peptide array. The viral genome analysis revealed two SARS-CoV-2 variants (20A from a deceased patient and an Alpha variant from a recovered patient) with an eight amino-acid (aa) deletion within the N-terminal domain (NTD) of the surface glycoprotein. A higher NAb titer was present against the prototypic USA/WA1/2020 strain in vaccinated immunocompromised patients. NAb titer was absent against the Omicron variant and the cultured virus of the 20A variant with eight aa deletions in non-vaccinated patients. Our data suggest that fatal SARS-CoV-2 infections may occur in immunocompromised individuals even with high titers of NAb post-vaccination. Moreover, persistent SARS-CoV-2 infection may lead to the emergence of newer variants with additional mutations favoring the survival and fitness of the pathogen that include deletions in NAb binding sites in the SARS-CoV-2 surface glycoprotein.     

Normative data of retinal arteriolar and venular calibre measurements determined using confocal scanning laser ophthalmoscopy system – Importance and implications for study of cardiometabolic disorders

Purpose:To determine and validate retinal vascular caliber measurements by using the confocal scanning laser ophthalmoscopy system. Retinal vasculature changes are often regarded as clinical markers for systemic disease.Methods:It was a prospective observational study conducted on 600 eyes of 300 normal subjects with no systemic or ocular illness from January 1, 2016 to June 30, 2017 in a tertiary referral eye center. Non-mydriatic infrared reflectance, blue reflectance, and blue peak blue autofluorescence fundus imaging were done on the confocal scanning laser ophthalmoscopy system. The dimensions of the retinal vessels were measured using inbuilt calipers at 1800 mm from the center of the optic disc. Internal and external dimensions were measured. Observer variation and its comparison using Image J software were assessed.Results:The median age was 29 years (18–50 years). Mean internal and external diameters for arterioles were 85.1 ± 12.4 mm and 105.0 ± 12.0 mm, and for venules were 133.8 ± 16.6 mm and 145.4 ± 16.1 mm, respectively. The mean internal and external wall thicknesses were 19.7 ± 8.0 mm and 11.0 ± 5.6 mm, and wall thickness-to-lumen ratios were 0.3 ± 0.1 and 0.1 ± 0.1, respectively. Arteriolar-to-venular ratio for lumen and vessel was 0.66 ± 0.1 and 0.74 ± 0.1, respectively. There was no statistically significant difference between age groups. Both inter- and intra-observer reproducibility was >95%. The Bland–Altman plot showed that the difference between measurements using both confocal scanning laser ophthalmoscopy and Image J software lies within the limits of agreement approximately 95% of the time.Conclusion:This is the first effort to develop a normative database by using a simple non-invasive confocal scanning laser ophthalmoscopy system with high observer reproducibility.     

Acoustic characterization of a miniature matrix transducer for pediatric 3D transesophageal echocardiography

This paper presents the design, fabrication and characterization of a miniature PZT-on-CMOS matrix transducer for real-time pediatric 3-dimensional (3D) transesophageal echocardiography (TEE). This 3D TEE probe consists of a 32?×?32 array of PZT elements integrated on top of an Application Specific Integrated Circuit (ASIC). We propose a partitioned transmit/receive array architecture wherein the 8?×?8 transmitter elements, located at the centre of the array, are directly wired out and the remaining receive elements are grouped into 96 sub-arrays of 3?×?3 elements. The echoes received by these sub-groups are locally processed by micro-beamformer circuits in the ASIC that allow pre-steering up to ±37°. The PZT-on-CMOS matrix transducer has been characterized acoustically and has a centre frequency of 5.8 MHz, -6 dB bandwidth of 67%, a transmit efficiency of 6 kPa/V at 30 mm, and a receive dynamic range of 85 dB with minimum and maximum detectable pressures of 5 Pa and 84 kPa respectively. The properties are very suitable for a miniature pediatric real-time 3D TEE probe.     

Phosphorylation of rat aquaporin‐4 at Ser111 is not required for channel gating

Aquaporin 4 (AQP4) is the predominant water channel in the mammalian brain and is mainly expressed in the perivascular glial endfeet at the brain‐blood interface. AQP4 has been described as an important entry and exit site for water during formation of brain edema and regulation of AQP4 is therefore of therapeutic interest. Phosphorylation of some aquaporins has been proposed to regulate their water permeability via gating of the channel itself. Protein kinase (PK)‐dependent phosphorylation of Ser¹¹¹ has been reported to increase the water permeability of AQP4 expressed in an astrocytic cell line. This possibility was, however, questioned based on the crystal structure of the human AQP4. Our study aimed to resolve if Ser¹¹¹ was indeed a site involved in phosphorylation‐mediated gating of AQP4. The water permeability of AQP4‐expressing Xenopus oocytes was not altered by a range of activators and inhibitors of PKG and PKA. Mutation of Ser¹¹¹ to alanine or aspartate (to prevent or mimic phosphorylation) did not change the water permeability of AQP4. PKG activation had no effect on the water permeability of AQP4 in primary cultures of rat astrocytes. Molecular dynamics simulations of a phosphorylation of AQP4.Ser¹¹¹ recorded no phosphorylation‐induced change in water permeability. A phospho‐specific antibody, exclusively recognizing AQP4 when phosphorylated on Ser¹¹¹, failed to detect phosphorylation in cell lysate of rat brain stimulated by conditions proposed to induce phosphorylation of this residue. Thus, our data indicate a lack of phosphorylation of Ser¹¹¹ and of phosphorylation‐dependent gating of AQP4.