Male Circumcision Complications - A Systematic Review, Meta-Analysis and Meta-Regression.

OBJECTIVE: To determine the risk of complications requiring treatment following male circumcision by health-care professionals and to explore the impact of participant characteristics, type of circumcision and study design. METHODS: We identified studies through systematic searches in online databases (MEDLINE, EMBASE and CENTRAL) and hand searches. We performed random-effects meta-analysis to determine risk of circumcision complications and mixed-effects metaregression analyses to explore the impact of participant characteristics, type of circumcision and study design. Methods were prespecified in a registered protocol (Prospero CRD42020116770) and according to PRISMA guidelines. RESULTS: We included 351 studies with 4.042.988 participants. Overall complication risk was 3.84% (95% confidence interval 3.35-4.37). Our meta-analysis revealed that therapeutic circumcisions were associated with a 2-fold increase in complications as compared to nontherapeutic (7.47% and 3.34%, respectively). Adhesions, meatal stenosis and infections were the most frequent complication subgroups to therapeutic circumcisions. Bleeding, device removals and infections occurred more frequently in nontherapeutic circumcisions. Additionally, adjusted metaregression analyses revealed that children above 2 years, South American continent, older publication year and smaller study populations increased complication risk. Type of circumcision method, provider and setting were not associated with complication risk. Sensitivity analyses including only better-quality studies reporting indication, age at circumcision, treatment for complications, full-text articles, and adequate follow-up clinically for a minimum of one month or through databases confirmed our main findings while accounting better for heterogeneity. CONCLUSION: Circumcision complications occur in about 4 per hundred circumcisions. Higher risks of complications were determined by therapeutic circumcisions and by childhood age when compared to infant. Future studies should assess therapeutic and childhood circumcisions separately.

Plant growth responses to elevated atmospheric CO2 are increased by phosphorus sufficiency but not by arbuscular mycorrhizas.

Capturing the full growth potential in crops under future elevated CO2 (eCO2) concentrations would be facilitated by improved understanding of eCO2 effects on uptake and use of mineral nutrients. This study investigates interactions of eCO2, soil phosphorus (P), and arbuscular mycorrhizal (AM) symbiosis in Medicago truncatula and Brachypodium distachyon grown under the same conditions. The focus was on eCO2 effects on vegetative growth, efficiency in acquisition and use of P, and expression of phosphate transporter (PT) genes. Growth responses to eCO2 were positive at P sufficiency, but under low-P conditions they ranged from non-significant in M. truncatula to highly significant in B. distachyon Growth of M. truncatula was increased by AM at low P conditions at both CO2 levels and eCO2×AM interactions were sparse. Elevated CO2 had small effects on P acquisition, but enhanced conversion of tissue P into biomass. Expression of PT genes was influenced by eCO2, but effects were inconsistent across genes and species. The ability of eCO2 to partly mitigate P limitation-induced growth reductions in B. distachyon was associated with enhanced P use efficiency, and requirements for P fertilizers may not increase in such species in future CO2-rich climates.

Arabidopsis MAP kinase 4 regulates gene expression through transcription factor release in the nucleus.

Plant and animal perception of microbes through pathogen surveillance proteins leads to MAP kinase signalling and the expression of defence genes. However, little is known about how plant MAP kinases regulate specific gene expression. We report that, in the absence of pathogens, Arabidopsis MAP kinase 4 (MPK4) exists in nuclear complexes with the WRKY33 transcription factor. This complex depends on the MPK4 substrate MKS1. Challenge with Pseudomonas syringae or flagellin leads to the activation of MPK4 and phosphorylation of MKS1. Subsequently, complexes with MKS1 and WRKY33 are released from MPK4, and WRKY33 targets the promoter of PHYTOALEXIN DEFICIENT3 (PAD3) encoding an enzyme required for the synthesis of antimicrobial camalexin. Hence, wrky33 mutants are impaired in the accumulation of PAD3 mRNA and camalexin production upon infection. That WRKY33 is an effector of MPK4 is further supported by the suppression of PAD3 expression in mpk4-wrky33 double mutant backgrounds. Our data establish direct links between MPK4 and innate immunity and provide an example of how a plant MAP kinase can regulate gene expression by releasing transcription factors in the nucleus upon activation.