79; 95% CI, 0.69-0.90; p less then 0.01; I2 = 0.0%), no significant reduction in 3P-MACE was observed with SGLT-2i in presence of background metformin therapy (N = 27,081; HR 0.94; 95% CI, 0.86-1.02; p = 0.13; I2 = 0.0%) with a significant Pheterogenity of 0.03 between the two groups. Similar finding was observed from the pooled results from 4 CVOTs. This may suggest that background metformin therapy may undermine the 3P-MACE benefit of SGLT-2i. However, no such interaction was observed in a recent meta-analysis of SGLT-2i, with or without background metformin therapy. Future research is warranted to understand the CV interaction of metformin with SGLT-2i.
  To compare pediatric ambulatory blood pressure monitoring (ABPM) criteria with adult ABPM criteria for the diagnosis of hypertension and detection of left ventricular hypertrophy (LVH) in adolescents.
 
  ABPM and echocardiography reports from adolescents age 13-21years from 2015 to 2019 were analyzed. The concordance of hypertension based on pediatric criteria (American Heart Association 2014) was compared with adult criteria from American College of Cardiology/American Heart Association 2017 (overall BP≥125/75mm Hg, wake BP≥130/80mm Hg, sleep BP≥110/65mm Hg) using the Cohen kappa statistic. Logistic regression, adjusted for body mass index z score, and receiver operating characteristic curves (ROCs) compared pediatric criteria vs adult criteria in predicting LVH (left ventricular mass index >95th percentile reference values and left ventricular mass index >51g/m
  ).
 
  Of 306 adolescents, 140 (45.8%) had hypertension based on pediatric criteria vs 228 (74.5%) based on adult criteria; the agreement was red a higher prevalence of LVH and appeared to predict better LVH than pediatric criteria. A consideration to align ABPM criteria for diagnosing hypertension in adolescents with adult guidelines is warranted.
  To investigate the relationships between dietary intake and fecal concentrations of milk fat globule-epidermal growth factor 8 (MFG-E8), and between fecal concentrations of MFG-E8 and markers of intestinal inflammation in infants born preterm.
 
  Fecal samples were collected daily and enteral feedings were sampled weekly. MFG-E8 in enteral feedings and feces, and cytokine concentrations in feces were quantified by enzyme-linked immunosorbent assay.
 
  Milk MFG-E8 concentrations were significantly greater in unfortified mother's own milk (MOM) and MOM with human milk fortifier than either donor human milk or preterm formula. MFG-E8 concentrations in fecal samples were positively correlated with MFG-E8 concentrations in respective milks. High MFG-E8 exposure (≥60mL/kg/day of feedings that include MOM or MOM with human milk fortifier) was associated with lower concentrations of proinflammatory cytokines (interleukin-8, tumor necrosis factor-α, and monocyte chemoattractant protein-1) and higher concentrations of the anti-inflammatory cytokine interleukin-4 in feces, compared with low MFG-E8 exposure.
 
  Infants born preterm who were fed MOM had greater concentrations of MFG-E8 and lower concentrations of proinflammatory cytokines in fecal samples than other diets or no feedings. These data further support the protective role of MOM, possibly because of MFG-E8, against intestinal inflammation.
 Infants born preterm who were fed MOM had greater concentrations of MFG-E8 and lower concentrations of proinflammatory cytokines in fecal samples than other diets or no feedings. These data further support the protective role of MOM, possibly because of MFG-E8, against intestinal inflammation.Cardiocerebrovascular disease is a collective term for cardiovascular and cerebrovascular diseases. Because of the complex mechanisms involved in cardiocerebrovascular diseases, limited effective treatments have been developed. With advancements in precision medicine, studies have focused on long noncoding RNAs (lncRNAs) in cerebrovascular diseases. LncRNAs, which are over 200 nucleotides long, regulate gene expression at epigenetic, transcriptional, and post-transcriptional levels. Moreover, lncRNAs play pivotal roles in the progression of cardiocerebrovascular diseases. For example, recent studies suggested that abnormal expression of lncRNAs are closely related to the occurrence and progression of these diseases. LncRNAs regulate gene expression by specifically binding to mRNA to modulate disease progression, serving as biomarkers for the diagnosis and prognosis of cardiocerebrovascular diseases. In this review, we discuss the roles, mechanisms, and clinical value of lncRNAs in cardiocerebrovascular diseases, providing a new perspective for the diagnosis and treatment of the diseases.Capsaicin, the pungent ingredient in chili peppers, produces intense burning pain in humans. Capsaicin selectively activates the transient receptor potential vanilloid 1 (TRPV1), which is enriched in nociceptive primary afferents, and underpins the mechanism for capsaicin-induced burning pain. Paradoxically, capsaicin has long been used as an analgesic. The development of topical patches and injectable formulations containing capsaicin has led to application in clinical settings to treat chronic pain conditions, such as neuropathic pain and the potential to treat osteoarthritis. More detailed determination of the neurobiological mechanisms of capsaicin-induced analgesia should provide the logical rationale for capsaicin therapy and help to overcome the treatment's limitations, which include individual differences in treatment outcome and procedural discomfort. Low concentrations of capsaicin induce short-term defunctionalization of nociceptor terminals. This phenomenon is reversible within hours and, hence, likely does not account for the clinical benefit. By contrast, high concentrations of capsaicin lead to long-term defunctionalization mediated by the ablation of TRPV1-expressing afferent terminals, resulting in long-lasting analgesia persisting for several months. Recent studies have shown that capsaicin-induced Ca2+/calpain-mediated ablation of axonal terminals is necessary to produce long-lasting analgesia in a mouse model of neuropathic pain. In combination with calpain, axonal mitochondrial dysfunction and microtubule disorganization may also contribute to the longer-term effects of capsaicin.  https://www.selleckchem.com/products/bp-1-102.html  The analgesic effects subside over time in association with the regeneration of the ablated afferent terminals. Further determination of the neurobiological mechanisms of capsaicin-induced analgesia should lead to more efficacious non-opioidergic analgesic options with fewer adverse side effects.