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Background Hypertension is a major source of cardiovascular morbidity and mortality. Recent evidence from mouse models, genetic, and cross-sectional human studies suggest increased proportions of selected immune cell subsets may be associated with levels of systolic blood pressure (SBP). Methods We assayed immune cells from cryopreserved samples collected at the baseline examination (2000–2002) from 1195 participants from the multi-ethnic study of atherosclerosis (MESA). We used linear mixed models, with adjustment for age, sex, race/ethnicity, smoking, exercise, body mass index, education, diabetes, and cytomegalovirus titers, to estimate the associations between 30 immune cell subsets (4 of which were a priori hypotheses) and repeated measures of SBP (baseline and up to four follow-up measures) over 10 years. The analysis provides estimates of the association with blood pressure level. Results The mean age of the MESA participants at baseline was 64 ± 10 years and 53% were male. A one standard deviation (1-SD) increment in the proportion of γδ T cells was associated with 2.40 mmHg [95% confidence interval (CI) 1.34–3.42] higher average systolic blood pressure; and for natural killer cells, a 1-SD increment was associated with 1.88 mmHg (95% CI 0.82–2.94) higher average level of systolic blood pressure. A 1-SD increment in classical monocytes (CD14 ++ CD16 − ) was associated with 2.01 mmHG (95% CI 0.79–3.24) lower average systolic blood pressure. There were no associations of CD4 + T helper cell subsets with average systolic blood pressure. Conclusion These findings suggest that the innate immune system plays a role in levels of SBP whereas there were no associations with adaptive immune cells.

Background The pediatric complex chronic conditions (CCC) classification system, developed in 2000, requires revision to accommodate the International Classification of Disease 10th Revision (ICD-10). To update the CCC classification system, we incorporated ICD-9 diagnostic codes that had been either omitted or incorrectly specified in the original system, and then translated between ICD-9 and ICD-10 using General Equivalence Mappings (GEMs). We further reviewed all codes in the ICD-9 and ICD-10 systems to include both diagnostic and procedural codes indicative of technology dependence or organ transplantation. We applied the provisional CCC version 2 (v2) system to death certificate information and 2 databases of health utilization, reviewed the resulting CCC classifications, and corrected any misclassifications. Finally, we evaluated performance of the CCC v2 system by assessing: 1) the stability of the system between ICD-9 and ICD-10 codes using data which included both ICD-9 codes and ICD-10 codes; 2) the year-to-year stability before and after ICD-10 implementation; and 3) the proportions of patients classified as having a CCC in both the v1 and v2 systems. Results The CCC v2 classification system consists of diagnostic and procedural codes that incorporate a new neonatal CCC category as well as domains of complexity arising from technology dependence or organ transplantation. CCC v2 demonstrated close comparability between ICD-9 and ICD-10 and did not detect significant discontinuity in temporal trends of death in the United States. Compared to the original system, CCC v2 resulted in a 1.0% absolute (10% relative) increase in the number of patients identified as having a CCC in national hospitalization dataset, and a 0.4% absolute (24% relative) increase in a national emergency department dataset. Conclusions The updated CCC v2 system is comprehensive and multidimensional, and provides a necessary update to accommodate widespread implementation of ICD-10.

Since implementation of the International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) in the US, thousands of new or related codes have been added to represent clinical conditions. The widely used pediatric complex chronic condition (CCC) system required a major update from version 2 (V2) to version 3 (V3) to capture the range of clinical conditions represented in the ICD-10-CM. To update the CCC V3 system, creating V3, with new, missing, or retired codes; to reconceptualize the system's use of technology codes; and to compare CCC V3 with V2. This repeated cross-sectional study examined US hospitalization data from the Pediatric Health Information System (PHIS) and the Medicaid Merative MarketScan Research Databases from January 1, 2009, to December 31, 2019, for all patients aged 0 to 18 years. Data were analyzed from March 1, 2023, to April 1, 2024. The CCCs were identified in both data sources using the CCC V2 and V3 systems. The (1) percentage of pediatric hospitalizations associated with a CCC, (2) numbers of CCC body-system categories per patient, and (3) explanatory power for hospital length of stay and in-hospital mortality were compared over time for V3 vs V2. Among 7 186 019 hospitalizations within PHIS, 54.3% patients were male, the median age was 4 years (IQR, 1-11 years), and 51.2% were aged 0 to 4 years). The CCC V2 identified 2 878 476 (40.1%) patients as having any CCC compared with 2 753 412 (38.3%) identified by V3. In addition, V2 identified 100 065 (1.4%) patients with transplant status compared with 146 683 (2.0%) by V3, and V2 identified 914 835 (12.7%) as having technology codes compared with 805 585 (11.2%) by V3. The 2 systems were similar in accounting for the number of CCC body-system categories per patient and in explaining variation in hospital length of stay and in-hospital mortality. For both V2 and V3, 10.0% of the variance in hospital length of stay and 12.0% of the variance in in-hospital mortality was explained by the presence of a CCC. Similar patterns were observed when analyzing the 2 999 420 Medicaid Merative MarketScan Research Databases' hospitalizations (52.3% of patients were male, the median age was 1 year [IQR, 0-12 years], and 62.0% were 0 to 4 years old), except that the percentages of identified CCCs were all lower: V2 identified 758 110 hospitalizations (25.3%) with any CCC compared with 718 100 (23.9%) identified by V3. These results suggest that, moving forward, V3 should be used to identify CCCs, and ongoing, frequent updates to V3, using a transparent, structured process, will enable V3 to accurately reflect the evolving spectrum of clinical conditions represented in the ICD-10-CM.

To identify pediatric age groups, medical subject headings (MeSH) categories for “Child”, “Infant”, and “Adolescent” were used with Boolean operators (Fig. 1). Across clinical topic areas for “Infant” RCTs, gastroenterology/hepatology, cardiology, pulmonary medicine, neurology, and obstetrics/gynecology had more yearly publications compared to other specialties, whereas psychiatry and neurology had substantially more RCTs for “Children” (Fig. 2A–B). Efforts to mandate trial reporting, to address barriers to high-quality research, and to ensure focus on RCTs to inform appropriate SRMAs require further attention.CRediT authorship contribution statement Joshua D. Niforatos: Conceptualization, Formal analysis, Investigation, Methodology, Project administration, Writing - original draft, Writing - review & editing.

Notch signaling is active during the development of mosaic epithelial sheets and during their turnover and regeneration. After the loss of hair cells in the mosaic sheet of the vestibular sensory epithelium, new hair cells can be spontaneously generated by transdifferentiation of supporting cells. This regenerative process involves downregulation of the Hes5 gene and is known to be limited and incomplete, especially when the lesion is severe. Here, we test whether further downregulation of Hes5 gene accomplished by the use of siRNA after a severe lesion induced by an aminoglycoside in the mouse utricle can enhance the transdifferentiation of supporting cells and lead to the increased production of new hair cells. We demonstrate that Hes5 levels in the utricle decreased after the application of siRNA and that the number of hair cells in these utricles was significantly larger than following control treatment. The data suggest that siRNA technology may be useful for inducing repair and regeneration in the inner ear and that the Notch signaling pathway is a potentially useful target for specific gene expression inhibition.

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