METHODS: In this work, we present a general overview of INPST activities and showcase the specific use of Twitter as a powerful networking tool that was used to host a one-week "2021 INPST Twitter Networking Event" (spanning from 31st May 2021 to 6th June 2021) based on the application of the Twitter hashtag #INPST.
RESULTS AND CONCLUSION: The use of this hashtag during the networking event period was analyzed with Symplur Signals (https://www.symplur.com/), revealing a total of 6,036 tweets, shared by 686 users, which generated a total of 65,004,773 impressions (views of the respective tweets). This networking event's achieved high visibility and participation rate showcases a convincing example of how this social media platform can be used as a highly effective tool to host virtual Twitter-based international biomedical research events.
OBJECTIVES: We aimed to establish the impact of including/excluding pregnancies with adverse neonatal outcomes when constructing GWG charts.
METHODS: This is an individual participant data analysis from 31 studies from low- and middle-income countries. We created a dataset that included all participants and a dataset restricted to those with no adverse neonatal outcomes: preterm < 37 wk, small or large for gestational age, low birth weight < 2500 g, or macrosomia > 4000 g. Quantile regression models were used to create GWG curves from 9 to 40 wk, stratified by prepregnancy BMI, in each dataset.
RESULTS: The dataset without the exclusion criteria applied included 14,685 individuals with normal weight and 4831 with overweight. After removing adverse neonatal outcomes, 10,479 individuals with normal weight and 3466 individuals with overweight remained. GWG distributions at 13, 27, and 40 wk were virtually identical between the datasets with and without the exclusion criteria, except at 40 wk for normal weight and 27 wk for overweight. For the 10th and 90th percentiles, the differences between the estimated GWG were larger for overweight (∼1.5 kg) compared with normal weight (<1 kg). Removal of adverse neonatal outcomes had minimal impact on GWG trajectories of normal weight. For overweight, the percentiles estimated in the dataset without the criteria were slightly higher than those in the dataset with the criteria applied. Nevertheless, differences were <1 kg and virtually nonexistent at the end of pregnancy.
CONCLUSIONS: Removing pregnancies with adverse neonatal outcomes has little or no influence on the GWG trajectories of individuals with normal and overweight.
Methods: Dermal fibroblast cultures were established from 2 affected men and 3 normals. Proliferation rates were examined, the collagen IV α5 chain localized with immunostaining, and levels of the intra- and extracellular chains quantitated with an in-house enzyme-linked immunosorbent assay. COL4A5 mRNA was measured using quantitative reverse transcriptase polymerase chain reaction. Endoplasmic reticulum (ER) size was measured on electron micrographs and after HSP47 immunostaining. Markers of ER stress (ATF6, HSPA5, DDIT3), autophagy (ATG5, BECN1, ATG7), and apoptosis (CASP3, BAD, BCL2) were also quantitated by quantitative reverse transcriptase polymerase chain reaction. Measurements were repeated after 48 hours of incubation with 10 mM sodium 4-phenylbutyrate acid.
Results: Both COL4A5 missense variants were associated with reduced proliferation rates on day 6 (P = 0.01 and P = 0.03), ER enlargement, and increased mRNA for ER stress and autophagy (all P values < 0.05) when compared with normal. Sodium 4-phenylbutyrate treatment increased COL4A5 transcript levels (P < 0.01), and reduced ER size (P < 0.01 by EM and P < 0.001 by immunostaining), ER stress (p HSPA5 and DDIT3, all P values < 0.01) and autophagy (ATG7, P < 0.01). Extracellular collagen IV α5 chain was increased in the M1 line only (P = 0.06).
Discussion: Sodium 4-phenylbutyrate increases collagen IV α5 mRNA levels, reduces ER stress and autophagy, and possibly facilitates collagen IV α5 extracellular transport. Whether these actions delay end-stage renal failure in men with X-linked Alport syndrome and missense mutations will only be determined with clinical trials.