Neutrophils and emergency granulopoiesis drive immune suppression and an extreme response endotype during sepsis.

Sepsis arises from diverse and incompletely understood dysregulated host response processes following infection that leads to life-threatening organ dysfunction. Here we showed that neutrophils and emergency granulopoiesis drove a maladaptive response during sepsis. We generated a whole-blood single-cell multiomic atlas (272,993 cells, n = 39 individuals) of the sepsis immune response that identified populations of immunosuppressive mature and immature neutrophils. In co-culture, CD66b+ sepsis neutrophils inhibited proliferation and activation of CD4+ T cells. Single-cell multiomic mapping of circulating hematopoietic stem and progenitor cells (HSPCs) (29,366 cells, n = 27) indicated altered granulopoiesis in patients with sepsis. These features were enriched in a patient subset with poor outcome and a specific sepsis response signature that displayed higher frequencies of IL1R2+ immature neutrophils, epigenetic and transcriptomic signatures of emergency granulopoiesis in HSPCs and STAT3-mediated gene regulation across different infectious etiologies and syndromes. Our findings offer potential therapeutic targets and opportunities for stratified medicine in severe infection.

The role of latitude and infections in the month-of-birth effect linked to schizophrenia.

There is an intriguing association between winter births and subsequent increased risk of schizophrenia. However, little is known about the environmental risk factors that contribute this month-of-birth effect. The aims of this study were to carry out a systematic review and meta-analysis of studies investigating the month-of-birth effect in schizophrenia and to explore possible factors such as latitude, daylight and infections that could explain this epidemiological observation. Medline, Embase and the Cochrane Library were searched for articles published up to December 23, 2021. Study selection, data extraction and analysis were undertaken according to Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. Generic inverse-variance with random effects models were used to determine the risk ratios (RR) and 95% confidence intervals (CI) for each month-of-birth. Associations between variables latitude and daylight were investigated using linear regression and Kendall's rank correlation coefficients were calculated assess the relationship between monthly infections rates schizophrenia births. Ten studies were included in the meta-analysis encompassing 262,188 schizophrenia patients. We identified significantly higher number of schizophrenia births in December [1.04 (95%CI 1.00-1.08)], January [1.06 (95%CI 1.03-1.1)] and February [1.03 (95%CI 1.00-1.05)]. We did not find any association between latitude and the magnitude of the month-of-birth effect. On the other hand, we found a significant negative correlation between monthly severe enterovirus cases and schizophrenia births (tau -0.57, p = 0.0099) using data from Taiwan. This highlights a role for enterovirus infections in mediating the month-of-birth effect in schizophrenia and these results carry implications for disease prevention strategies.

Malaria and Dengue Mosquito Vectors from Lao PDR Show a Lack of the rdl Mutant Allele Responsible for Cyclodiene Insecticide Resistance.

The gamma-aminobutyric acid (GABA) receptor, RDL, plays important roles in neuronal signaling and is the target of highly effective insecticides. A mutation in RDL, commonly A296S, underlies resistance to several insecticides such as cyclodienes. Even though the use of cyclodienes has been banned, the occurrence of mutations substituting A296 is notably high in mosquitoes from several countries. Here, we report a survey investigating the prevalence of the Rdl mutant allele in mosquitoes from Laos, a country where mosquito-borne diseases such as malaria and dengue fever are health concerns. Anopheles and Aedes mosquitoes were collected from 12 provinces in Laos. Adult bioassays on Aedes aegypti (Linnaeus) (Diptera: Culicidae) and Aedes albopictus (Skuse) (Diptera: Culicidae) showed that all the populations tested were susceptible to dieldrin (4%) following WHO protocols. Exon 7 from a total of 791 mosquitoes was sequenced to identify the amino acid encoded for at 296 of RDL. Only one of these mosquitoes, Anopheles maculatus rampae Harbach and Somboon (Diptera: Culicidae) from Attapeu, carried the mutant allele being heterozygous for A296S. We therefore found a general lack of the Rdl mutant allele indicating that mosquitoes from Laos are not exposed to insecticides that act on the GABA receptor compared to mosquitoes in several other countries. Identifying the prevalence of the Rdl mutation may help inform the potential use of alternative insecticides that act on the GABA receptor should there be a need to replace pyrethroids in order to prevent/manage resistance.