Pooled rates and demographics of POTS following SARS-CoV-2 infection versus COVID-19 vaccination: Systematic review and meta-analysis.

PURPOSE: To address recent concerns of postural orthostatic tachycardia syndrome (POTS) occurring after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination. METHODS: We searched PubMed, Web of Science, and Scopus as of 1st June 2023. We performed a systematic review and meta-analysis of pooled POTS rate in SARS-CoV-2-infected and COVID-19-vaccinated groups from epidemiological studies, followed by subgroup analyses by characteristic. Meta-analysis of risk ratio was conducted to compare POTS rate in infected versus uninfected groups. Meta-analysis of demographics was also performed to compare cases of post-infection and post-vaccination POTS from case reports and series. RESULTS: We estimated the pooled POTS rate of 107.75 (95 % CI: 9.73 to 273.52) and 3.94 (95 % CI: 0 to 16.39) cases per 10,000 (i.e., 1.08 % and 0.039 %) in infected and vaccinated individuals based on 5 and 2 studies, respectively. Meta-regression revealed age as a significant variable influencing 86.2 % variance of the pooled POTS rate in infected population (P < 0.05). Moreover, POTS was 2.12-fold more likely to occur in infected than uninfected individuals (RR = 2.12, 95 % CI: 1.71 to 2.62, P < 0.001). Meta-analyzed demographics for cases of post-infection (n = 43) and post-vaccination (n = 17) POTS found no significant differences in several variables between groups, except that the time from exposure to symptom onset was shorter for cases of post-vaccination POTS (P < 0.05). CONCLUSION: Although evidence is limited for post-vaccination POTS, our study showed that POTS occur more frequently following SARS-CoV-2 infection than COVID-19 vaccination.

Evaluation of the Antiasthmatic Activity of Carissa opaca in Animal Models.

Carissa opaca Stapf ex Haines (C. opaca) fruit is used traditionally in the treatment of respiratory illnesses including asthma. However, there is no scientific evidence supporting its antiasthmatic activity. The current study was conducted to evaluate its antiasthmatic effects using in vivo and in vitro approaches. The methanolic crude extract of C. opaca fruit (Co.Cr.) was used and in vivo antiasthmatic activity was carried out using ovalbumin- (OVA-) sensitized and OVA-challenged BALB/c mice. In in vitro bronchorelaxant activity of crude extract, aqueous and n-hexane fractions of C. opaca were carried out on isolated rat tracheal strips. Co.Cr. (200 and 400 mg/kg) attenuated ovalbumin-induced changes in lung histochemistry with % decrease in peribronchial inflammation of 14.1 ± 0.21 and 65.8 ± 0.22 and % decrease in total inflammatory cell count of 35.7 ± 2.80 and 53.3 ± 2.30 in bronchoalveolar lavage fluid. Co.Cr., aqueous, and n-hexane fraction of C. opaca attenuated the precontractions induced by high K+ (80 mM) and carbachol (1 µM), respectively. In conclusion, the results showed that C. opaca possesses antiasthmatic activity via relaxant effect on bronchial smooth muscle which is mediated through calcium channel blockade and antimuscarinic activity. This study provides scientific evidence of the traditional use of C. opaca in the management of allergic asthma.

Dimerization of the Sodium/Iodide Symporter.

Background: The ability of thyroid follicular epithelial cells to accumulate iodide via the sodium/iodide symporter (NIS) is exploited to successfully treat most thyroid cancers, although a subset of patients lose functional NIS activity and become unresponsive to radioiodide therapy, with poor clinical outcome. Our knowledge of NIS regulation remains limited, however. While numerous membrane proteins are functionally regulated via dimerization, there is little definitive evidence of NIS dimerization, and whether this might impact upon radioiodide uptake and treatment success is entirely unknown. We hypothesized that NIS dimerizes and that dimerization is a prerequisite for iodide uptake. Methods: Coimmunoprecipitation, proximity ligation, and Förster resonance energy transfer (FRET) assays were used to assess NIS:NIS interaction. To identify residues involved in dimerization, a homology model of NIS structure was built based on the crystal structure of the dimeric bacterial protein vSGLT. Results: Abundant cellular NIS dimerization was confirmed in vitro via three discrete methodologies. FRET and proximity ligation assays demonstrated that while NIS can exist as a dimer at the plasma membrane (PM), it is also apparent in other cellular compartments. Homology modeling revealed one key potential site of dimeric interaction, with six residues <3Å apart. In particular, NIS residues Y242, T243, and Q471 were identified as critical to dimerization. Individual mutation of residues Y242 and T243 rendered NIS nonfunctional, while abrogation of Q471 did not impact radioiodide uptake. FRET data show that the putative dimerization interface can tolerate the loss of one, but not two, of these three clustered residues. Conclusions: We show for the first time that NIS dimerizes in vitro, and we identify the key residues via which this happens. We hypothesize that dimerization of NIS is critical to its trafficking to the PM and may therefore represent a new mechanism that would need to be considered in overcoming therapeutic failure in patients with thyroid cancer.