Studies of CP Prevalence: Disparities in Authorship, Citations, and Geographic Location.

We aimed to characterize the existing knowledge of cerebral palsy (CP) prevalence globally and identify any existing publication disparities that may impact our understanding of the global burden of CP. To identify existing publications on CP prevalence, PubMed and Web of Science were searched in May 2021 with the following strategy: "cerebral palsy"[title] AND (rate OR prevalence OR epidemiology). This search yielded 2720 results on PubMed and 2314 on Web of Science. Studies published in English, Spanish, or Japanese and which were available in full text were included. Studies that did not report a CP prevalence statistic were excluded. We identified 94 studies meeting inclusion and exclusion criteria. Of 94 studies, 69 (73.4%) studies came from Europe, North America, and Australia with the remaining 25 (26.6%) from Asia, the Middle East, and Africa. No studies from Latin America were identified. CP prevalence estimates ranged from 0.8 to 4.4 per 1000 live births. Studies from Europe are cited more than studies from other regions, ranging from 7.61 citations/year since publication for European studies to 2.1 citations/year for Middle Eastern studies. Studies from Western countries are written almost exclusively by Western authors (99.69%-100%), while studies from Africa consist of a lower proportion of African authors (31.06%). Our results highlight geographical disparities in our knowledge of CP epidemiology. Existing literature from Latin America, Asia, Africa, and the Middle East are relatively undercited by the field. To better grasp the true impact of CP globally, we must support institutions and researchers in underrepresented regions of the world.

Estrogen May Enhance Toll-Like Receptor 4-Induced Inflammatory Pathways in People With HIV: Implications for Transgender Women on Hormone Therapy.

Background: Transgender women (TW) are at increased risk for both human immunodeficiency virus (HIV) and cardiovascular disease (CVD). Antiretroviral therapy-treated HIV has been associated with a two-fold increased risk of CVD, potentially due to dysregulated Toll-like receptor (TLR)-induced immune activation. Use of estrogens in feminizing hormone therapy (FHT) may enhance inflammatory responses and the risk of cardiovascular mortality in TW. Despite this, the immunomodulatory effects of estrogen use in TW with HIV have been inadequately explored. Methods: As an in vitro model for FHT, cryopreserved PBMCs (cryoPBMCs) from HIV negative (HIV-), HIV+ ART-suppressed (HIV+SP), and HIV+ ART-unsuppressed (HIV+USP) cisgender men were cultured overnight in the presence of 17-ß estradiol or 17-α ethinylestradiol with and without the TLR4 agonist LPS or the TLR8 agonist ssPolyU. Monocyte activation (CD69, HLA-DR, CD38) was assessed by flow cytometry. Cytokine levels (IL-6, TNF-α, IL-1ß, and IL-10) were measured in cell culture supernatants by Legendplex. Levels of phosphorylated TLR signaling molecules (JNK, MAPK p38) were assessed by Phosflow. Plasma levels of immune activation biomarkers (LPS-binding protein, monocyte activation markers sCD14 and sCD163, and inflammatory molecules IL-6 and TNF-α receptor I) were measured by ELISA. Results: PBMCs from people with HIV (PWH) produced greater levels of inflammatory cytokines following exposure to LPS or ssPolyU compared to levels from cells of HIV- individuals. While estrogen exposure alone induced mild changes in immune activation, LPS-induced TLR4 activation was elevated with estrogen in cisgender men (CM) with HIV, increasing monocyte activation and inflammatory cytokine production (IL-6, TNF-α). Interestingly, testosterone inhibited LPS-induced cytokine production in CM regardless of HIV status. Plasma markers of immune activation and microbial translocation (e.g., sCD14, sCD163, LPS-binding protein) were generally higher in PWH compared to HIV- CM, and these markers were positively associated with in vitro responsiveness to estrogen and LPS in CM with HIV. Conclusions: Our in vitro data suggest that estrogen exposure may enhance innate immune activation in PWH. Further examination is needed to fully understand the complex interactions of FHT, HIV, and CVD in TW, and determine optimal FHT regimens or supplementary treatments aimed at reducing excess immune activation.