6-3.9]), and nonusers (3.8 [3.7-4.0]). The aHR for DPN was 1.05 (0.98-1.11) in new users and 0.97 (0.91-1.04) in prevalent users compared with statin nonusers. New users had a slightly increased DPN risk during the first year (1.31 [1.12-1.53]), which vanished after >2 years of follow-up. Findings were similar in on-treatment and propensity score-matched analyses and with additional adjustment for pretreatment blood lipid levels.
 
  Statin therapy is unlikely to increase or mitigate DPN risk in patients with type 2 diabetes, although a small acute risk of harm cannot be excluded.
 Statin therapy is unlikely to increase or mitigate DPN risk in patients with type 2 diabetes, although a small acute risk of harm cannot be excluded.
  To assess the association between daily carbohydrate (CHO) intake and glycemic control in adult hybrid closed-loop (HCL) users with type 1 diabetes (T1D).
 
  Mean individual daily CHO intake (MIDC) and relative deviation from MIDC (≤80% low, 81-120% medium, >120% high CHO consumption) were compared with parameters of glycemic control assessed by continuous glucose monitoring.
 
  Records from 36 patients (26 male, 10 female; age 36.9 ± 13.5 years; HbA
  7.1 ± 0.9% [54 ± 10 mmol/mol]) provided 810 days of data (22.5 ± 6.7 days per patient). Time in range (70-180 mg/dL) for low, medium, and high CHO consumption was 77.4 ± 15.4%, 75.2 ± 16.7%, and 70.4 ± 17.8%, respectively (
  < 0.001). Time above range (>180 mg/dL) was 20.1 ± 14.7%, 22.0 ± 16.9%, and 27.2 ± 18.4%, respectively (
  < 0.001). There was no between-group difference for time in hypoglycemia (<70 mg/dL; 
  = 0.50).
 
  Daily CHO intake was inversely associated with glycemic control in adults with T1D using an HCL system. Lower CHO intake may be a strategy to optimize glucose control in HCL users.
 Daily CHO intake was inversely associated with glycemic control in adults with T1D using an HCL system. Lower CHO intake may be a strategy to optimize glucose control in HCL users.
  The incidence of type 1 diabetes has been rising for decades, particularly among young children. Between 2006 and 2011, the incidence rate (IR) reached a plateau in Finland. In this observational, register-based cohort study, we assess recent trends in the disease rate in Finnish children.
 
  Based on data from the Finnish Pediatric Diabetes Register, we studied the incidence of type 1 diabetes among children younger than 15 years of age between 2003 and 2018. We assessed sex-specific IRs per 100,000 person-years (PY) by 4-year time periods in three age-groups (0.50-4.99, 5.00-9.99, and 10.00-14.99 years).
 
  Among the 7,871 children with newly diagnosed type 1 diabetes, the median age at diagnosis increased from 7.88 to 8.33 years (
  = 0.001), while the overall IR decreased from 57.9/100,000 PY in 2003-2006 to 52.2/100,000 PY in 2015-2018, yielding an IR ratio (IRR) of 0.90 (95% CI 0.85-0.96, 
  = 0.001).  https://www.selleckchem.com/products/pepstatin-a.html  This decline was mainly due to the decrease in the youngest age-group (IRR 0.77 [95% CI 0.68-0.87]; 
  < 0.001), being significant both among boys and girls. In the middle age-group, a significant decrease was observed only among girls. No changes were observed in the oldest children.
 
  The incidence of type 1 diabetes decreased among young Finnish children between 2003 and 2018. Current findings imply that environmental factors driving the immune system toward islet autoimmunity are changing in young children.
 The incidence of type 1 diabetes decreased among young Finnish children between 2003 and 2018. Current findings imply that environmental factors driving the immune system toward islet autoimmunity are changing in young children.Although the immune response is likely to play a pivotal role in controlling Kaposi sarcoma (KS)-associated herpesvirus (KSHV) and preventing disease development, the exact factors responsible for that control remain ill defined. T cell responses are weak and variable, and neutralizing Abs are more frequently detected in individuals with KS. This suggests a potential role for nonneutralizing Abs, which to date have been largely uninvestigated. Ab-dependent cell cytotoxicity (ADCC) is a common effector function for nonneutralizing Abs and is known to play a protective role in other herpesvirus infections; yet, ADCC has never been investigated in the context of KSHV infection. In this study, we provide, to our knowledge, the first evidence that anti-KSHV Abs are capable of mediating ADCC responses against infected human cells undergoing lytic reactivation. ADCC activity significantly higher than seronegative controls was detected in 24 of 68 KSHV-seropositive individuals tested. However, ADCC responses were not associated with KS development or progression. ADCC activity was also found to be independent of HIV status, sex, age, KSHV Ab titer, and KSHV-neutralizing activity. Nevertheless, additional investigations into effector cell function between KS and asymptomatic individuals are needed to determine whether ADCC has a role in preventing KS.CD8 T cell differentiation is orchestrated by dynamic metabolic changes that direct activation, proliferation, cytotoxic function, and epigenetic changes. We report that the BTB-ZF family transcriptional repressor Zbtb20 negatively regulates CD8 T cell metabolism and memory differentiation in mice. Effector and memory CD8 T cells with conditional Zbtb20 deficiency displayed enhanced mitochondrial and glycolytic metabolism, and memory CD8 T cells had enhanced spare respiratory capacity. Furthermore, Zbtb20-deficient CD8 T cells displayed increased flexibility in the use of mitochondrial fuel sources. Phenotypic and transcriptional skewing toward the memory fate was observed during the CD8 T cell response to Listeria monocytogenes Memory cells mounted larger secondary responses and conferred better protection following tumor challenge. These data suggest that inactivation of Zbtb20 may offer an approach to enhance metabolic activity and flexibility and improve memory CD8 T cell differentiation, useful attributes for T cells used in adoptive immunotherapy.BP180 (also termed type XVII collagen) is a hemidesmosomal protein and plays a critical role in cell-cell matrix adhesion in the skin; however, its other biological functions are largely unclear. In this study, we generated a BP180 functional-deficient mouse strain by deleting its extracellular domain of humanized NC16A (termed ΔNC16A mice). We found that BP180 is expressed by bone marrow mesenchymal stem cells (BM-MSC), and its functional deficiency leads to myeloid hyperplasia. Altered granulopoiesis in ΔNC16A mice is through bone marrow stromal cells evidenced by bone marrow transplantation. Furthermore, the level of G-CSF in bone marrow and circulation were significantly increased in ΔNC16A mice as compared with wild-type mice. The increased G-CSF was accompanied by an increased activation of the NF-κB signaling pathway in bone marrow and BM-MSC of ΔNC16A mice. Blockade of G-CSF restored normal granulopoiesis in ΔNC16A mice. Inhibition of NF-κB signaling pathway significantly reduces the release of G-CSF from ΔNC16A BM-MSC in vitro and the level of serum G-CSF in ΔNC16A mice.