An Increased Risk for Ischemic Stroke in the Short-Term Period following COVID-19 Infection: A Nationwide Population-Based Study.

INTRODUCTION: The association disclosed between coronavirus disease 2019 (COVID-19) infection and ischemic stroke (IS) raises concern. The exact risk periods, which were not consistent between studies, require further investigation. METHODS: We linked two national databases: the COVID-19 database and the Israeli National Stroke Registry. The self-controlled case series method was used to estimate the association between COVID-19 infection and a first IS. The study population included all Israeli residents who had both a first IS event and a first COVID-19 diagnosis during 2020. The date of the PCR test served to define the day of exposure, and the 28 days following it were categorized into three risk periods: days 1-7, 8-14, and 15-28. A relative incidence (RI) with a 95% confidence interval (95% CI) was calculated based on the incidence rate of events in a post-exposure period, compared to the incidence rate in a control period. RESULTS: From January 1, 2020, to December 31, 2020, 308,015 Israelis aged 18+ were diagnosed with COVID-19 and 9,535 were diagnosed with a first IS. Linking the two databases, 555 persons had both diagnoses during 2020. The mean age of the study population was 71.5 ± 13.7, 55.1% were males, 77.8% had hypertension, 73.7% had hyperlipidemia, 51.9% had diabetes, and 28.5% had ischemic heart disease. Comparing the risk period and the control period, we found a very similar distribution of the cardiovascular risk factors. The risk for an acute IS was 3.3-fold higher in the first week following COVID-19 diagnosis, compared with a control period (RI = 3.3; 95% CI: 2.3-4.6). The RI among males (RI = 4.5; 95% CI: 2.9-6.8) was 2.2-fold higher compared to females. The increased risk did not last beyond the first week following exposure. CONCLUSION: Physicians should be aware of the elevated risk for IS among patients experiencing COVID-19, particularly among men with high burden of cardiovascular risk factors.

Ferric reductase-related proteins mediate fungal heme acquisition.

Heme can serve as iron source in many environments, including the iron-poor animal host environment. The fungal pathobiont Candida albicans expresses a family of extracellular CFEM hemophores that capture heme from host proteins and transfer it across the cell wall to the cell membrane, to be endocytosed and utilized as heme or iron source. Here, we identified Frp1 and Frp2, two ferric reductase (FRE)-related proteins that lack an extracellular N-terminal substrate-binding domain, as being required for hemoglobin heme utilization and for sensitivity to toxic heme analogs. Frp1 and Frp2 redistribute to the plasma membrane in the presence of hemin, consistent with a direct role in heme trafficking. Expression of Frp1 with the CFEM hemophore Pga7 can promote heme utilization in Saccharomyces cerevisiae as well, confirming the functional interaction between these proteins. Sequence and structure comparison reveals that the CFEM hemophores are related to the FRE substrate-binding domain that is missing in Frp1/2. We conclude that Frp1/2 and the CFEM hemophores form a functional complex that evolved from FREs to enable extracellular heme uptake.

Hosts and disease-causing fungi are often locked into a battle over resources. The host will attempt to withhold molecules that the fungus needs to survive, while the pathogen will try to find alternative routes to obtain them. Candida albicans, for example, can go after the atoms of iron embedded in the proteins of the organism it infects. To do so it releases molecules known as hemophores, which scavenge the iron-containing heme molecule that equips oxygen-carrying proteins in the blood. Once captured, the heme is carried across the wall that protects C. albicans from the environment and brought to the membrane of the cell. It is then taken in and trafficked inside vesicles to its destination. However, the identity of the molecular actors which help to bridge the internal and external segments of the heme journey remain unclear. Previous studies have shown that the hemophore Pga7 is involved, but this protein is attached to the outside of the cell membrane, where it cannot directly interact with the import machinery. Roy et al. set out to discover this missing link. Examining the genomes of fungal species related to C. albicans highlighted two membrane proteins, Frp1 and Frp2, which could participate in heme uptake. Protein sequence comparison revealed that Frp1 and Frp2 were closely related to ferric reductases, a group of membrane enzymes which can chemically alter extracellular iron prior to uptake. Deleting the genes for Frp1 and Frp2 rendered C. albicans cells incapable of taking in heme. Conversely, a fungal species which cannot normally uptake heme could efficiently internalise these complexes when artificially equipped with Frp1 and Pga7, suggesting that the two proteins work closely together. Finally, protein structure comparisons highlighted that an extracellular domain present in ferric reductases but absent in Frp1 and Frp2 is, in fact, related to Pga7 and other hemophores. This implies that the iron and heme uptake systems may share a common evolutionary origin. Overall, the work by Roy et al. reveals a new family of proteins which allow disease-causing fungi to steal iron from their hosts. This knowledge may be useful to design better anti-fungal treatments.

Diverse heliorhodopsins detected via functional metagenomics in freshwater Actinobacteria, Chloroflexi and Archaea.

The recently discovered rhodopsin family of heliorhodopsins (HeRs) is abundant in diverse microbial environments. So far, the functional and biological roles of HeRs remain unknown. To tackle this issue, we combined experimental and computational screens to gain some novel insights. Here, 10 readily expressed HeR genes were found using functional metagenomics on samples from two freshwater environments. These HeRs originated from diverse prokaryotic groups: Actinobacteria, Chloroflexi and Archaea. Heterologously expressed HeRs absorbed light in the green and yellow wavelengths (543-562 nm) and their photocycles exhibited diverse kinetic characteristics. To approach the physiological function of the HeRs, we used our environmental clones along with thousands of microbial genomes to analyze genes neighbouring HeRs. The strongest association was found with the DegV family involved in activation of fatty acids, which allowed us to hypothesize that HeRs might be involved in light-induced membrane lipid modifications.

Overestimation of body weight and its association with parental, teacher and peer support: evidence from the Israeli Health Behaviours in Schools survey.

OBJECTIVE: To investigate the association between family, teachers and peer support patterns on gaps in adolescent's weight perceptions. DESIGN: A cross-sectional, school-based survey collected information on weight and height, weight perception, socio-economic and family characteristics and social support. Principal component analysis (PCA) was performed to capture social support patterns (SSP). Multivariable logistic regression was used to model adolescent weight perception, including SSP adjusted for demographic variables. SETTING: The 2014 Israeli Health Behaviours in School-Aged Children (HBSC) survey. PARTICIPANTS: Adolescents aged 11-18 years (n 7563). RESULTS: In total, 16·1 % of the boys and 10·7 % of the girls were overweight or obese. Most participants perceived their size accurately. Body size was underestimated by 25·6 % of the boys and 15·1 % of the girls, while 15·2 % of the boys and 27·7 % of the girls overestimated their body size. PCA generated three SSP accounting for 81·9 % of the variance in social support. Female sex and higher SES increased odds of overestimating body size. Students in the top quartile (Q4 v. Q1-Q3) of family support and teacher support were less likely to overestimate their body size. Good parental communication reduced the odds of body size overestimation in middle school students. Male sex and higher family support increased odds of underestimation. CONCLUSIONS: Significant support from parents and teachers was associated with accurate weight perceptions; thus, support skills may be amenable to intervention. Efforts should be made to educate adolescents on healthy weight.