Lung injury-induced activated endothelial cell states persist in aging-associated progressive fibrosis.

Progressive lung fibrosis is associated with poorly understood aging-related endothelial cell dysfunction. To gain insight into endothelial cell alterations in lung fibrosis we performed single cell RNA-sequencing of bleomycin-injured lungs from young and aged mice. Analysis reveals activated cell states enriched for hypoxia, glycolysis and YAP/TAZ activity in ACKR1+ venous and TrkB+ capillary endothelial cells. Endothelial cell activation is prevalent in lungs of aged mice and can also be detected in human fibrotic lungs. Longitudinal single cell RNA-sequencing combined with lineage tracing demonstrate that endothelial activation resolves in young mouse lungs but persists in aged ones, indicating a failure of the aged vasculature to return to quiescence. Genes associated with activated lung endothelial cells states in vivo can be induced in vitro by activating YAP/TAZ. YAP/TAZ also cooperate with BDNF, a TrkB ligand that is reduced in fibrotic lungs, to promote capillary morphogenesis. These findings offer insights into aging-related lung endothelial cell dysfunction that may contribute to defective lung injury repair and persistent fibrosis.

Single Cell Transcriptomics of Fibrotic Lungs Unveils Aging-associated Alterations in Endothelial and Epithelial Cell Regeneration.

Lung regeneration deteriorates with aging leading to increased susceptibility to pathologic conditions, including fibrosis. Here, we investigated bleomycin-induced lung injury responses in young and aged mice at single-cell resolution to gain insights into the cellular and molecular contributions of aging to fibrosis. Analysis of 52,542 cells in young (8 weeks) and aged (72 weeks) mice identified 15 cellular clusters, many of which exhibited distinct injury responses that associated with age. We identified Pdgfra + alveolar fibroblasts as a major source of collagen expression following bleomycin challenge, with those from aged lungs exhibiting a more persistent activation compared to young ones. We also observed age-associated transcriptional abnormalities affecting lung progenitor cells, including ATII pneumocytes and general capillary (gCap) endothelial cells (ECs). Transcriptional analysis combined with lineage tracing identified a sub-population of gCap ECs marked by the expression of Tropomyosin Receptor Kinase B (TrkB) that appeared in bleomycin-injured lungs and accumulated with aging. This newly emerged TrkB + EC population expressed common gCap EC markers but also exhibited a distinct gene expression signature associated with aberrant YAP/TAZ signaling, mitochondrial dysfunction, and hypoxia. Finally, we defined ACKR1 + venous ECs that exclusively emerged in injured lungs of aged animals and were closely associated with areas of collagen deposition and inflammation. Immunostaining and FACS analysis of human IPF lungs demonstrated that ACKR1 + venous ECs were dominant cells within the fibrotic regions and accumulated in areas of myofibroblast aggregation. Together, these data provide high-resolution insights into the impact of aging on lung cell adaptability to injury responses.

Lumbar intervertebral disc degeneration, end-plates and paraspinal muscle changes in children and adolescents with low-back pain.

The prevalence of low-back pain (LBP) in adolescents ranges from 7 to 72%. We aimed to define the radiologic characteristics of the lumbar spine in children and adolescents with LBP with/without leg pain. Two hundred and fourteen children and adolescents, who were born between 2001 and 2009 and had lumbar spine MRI for LBP with/without leg pain, were evaluated in terms of intervertebral disc degeneration (IVDD), end-plates and paraspinal muscle changes on lumbar spine MRIs. Severe IVDD was detected at all lumbar levels except for L2-L3. Modic changes were present in 4.2% of the patients. Modic changes were more common in patients with severe IVDD than in those with mild-to-moderate IVDD. Severe IVDD was significantly associated with Modic changes at the corresponding L1-L2 and L3-L4 disc levels. Girls had significantly more fatty infiltration in the paraspinal muscles when compared to boys. The risk of having severe IVDD concomitant with Modic changes was high [odds ratio (OR), 8.6]. The OR was 20.7 for predicting the presence of severe IVDD at any level if Modic changes presented particularly at the L3-L4 level. The ORs of Modic changes presented at any lumbar level at the background of fat-infiltrated multifidus at L3-L4 and L4-L5 levels were 8.3 and 9.1, respectively. Fatty infiltration in the paraspinal muscles and IVDD were closely associated with Modic changes in children and adolescents with LBP. Lumbar IVDD in children and adolescents could be the result of a mechanical pathology.

Schmorl's nodes could be associated with intervertebral disc degeneration at upper lumbar levels and end-plate disease at lower lumbar level in patients with low back pain.

Schmorl's nodes (SNs) have increasingly been recognized on vertebral end-plates using advanced imaging techniques. Even though vertebral end-plates are the closest structures to discs, their pathologies are underestimated in the etiology of low back pain (LBP). We aimed to detect the prevalence of SNs and other end-plate defects in subjects with/without LBP and to understand whether SNs were associated with LBP and spinal degeneration. Subjects were evaluated in terms of end-plate defects, intervertebral disc degeneration (IVDD), and vertebral end-plate changes (Modic changes) at all lumbar levels on lumbar spine magnetic resonance imagings (MRI). Control subjects were compared to patients with LBP. Higher Pfirrmann scores (OR: 2.696) and higher SN scores (OR: 8.076) were significantly associated with Modic changes at L4-L5 disc level. Patients with higher SN scores at L1-L2 or L2-L3 levels had approximately 7-fold increased risk of severe IVDD at the corresponding levels. The most significant factor associated with presence of SNs was body weight of the patients (OR: 1.417). The most significant factor associated with intensity of LBP was severe IVDD at L5-S1 level (OR: 3.670). Having higher total SN score had an OR of 1.230 (95% CI: 1.003-1.509; p = 0.047) for predicting LBP. Schmorl's nodes were seen in 33.1% of patients and 11.5% of asymptomatic subjects. Body weight was the most significant factor associated with SNs. The most significant factor associated with LBP was severe IVDD at L5-S1 level.

Early Postnatal Metabolic Profile in Neonates With Different Birth Weight Status: A Pilot Study.

Introduction: Restricted or enhanced intrauterine growth is associated with elevated risks of early and late metabolic problems in humans. Metabolomics based on amino acid and carnitine/acylcarnitine profile may have a role in fetal and early postnatal energy metabolism. In this study, the relationship between intrauterine growth status and early metabolomics profile was evaluated. Materials and Methods: A single-center retrospective cohort study was conducted. Three hundred and sixty-one newborn infants were enrolled into the study, and they were grouped according to their birth weight percentile as small for gestational age (SGA, n = 69), appropriate for gestational age (AGA, n = 168), and large for gestational age (LGA, n = 124) infants. In all infants, amino acid and carnitine/acylcarnitine profiles with liquid chromatography-tandem mass spectrometry (LC-MS/MS) were recorded and compared between groups. Results: LGA infants had higher levels of glutamic acid and lower levels of ornithine, alanine, and glycine (p < 0.05) when compared with AGA infants. SGA infants had higher levels of alanine and glycine levels when compared with AGA and LGA infants. Total carnitine, C0, C2, C4, C5, C10:1, C18:1, C18:2, C14-OH, and C18:2-OH levels were significantly higher and C3 and C6-DC levels were lower in SGA infants (p < 0.05). LGA infants had higher C3 and C5:1 levels and lower C18:2 and C16:1-OH levels (p < 0.05). There were positive correlations between free carnitine and phenylalanine, arginine, methionine, alanine, and glycine levels (p < 0.05). Also, a positive correlation between ponderal index and C3, C5-DC, C14, and C14:1 and a negative correlation between ponderal index and ornithine, alanine, glycine, C16:1-OH, and C18:2 were shown. Conclusion: We demonstrated differences in metabolomics possibly reflecting the energy metabolism in newborn infants with intrauterine growth problems in the early postnatal period. These differences might be the footprints of metabolic disturbances in future adulthood.

Learning curve analysis of robotic transabdominal preperitoneal inguinal hernia repair.

BACKGROUND: The purpose of this study was to assess the learning curve (LC) for inguinal hernia repair with robotic transabdominal preperitoneal (R-TAPP) approach. METHODS: Between April 2016 and October 2019, patients who underwent R-TAPP were retrieved. Patient demographics, operative variables and postoperative outcomes were assessed. The moving average method and cumulative sum of operation times (OT) were used to evaluate the LC. The surgeon (BB) in this study had completed his laparoscopic (Lap) TAPP experience. RESULTS: There were 50 (two females) consecutive patients (mean age was 51.7 ± 16.9 years). The first phase (learning phase) included initial 35 operations. The second phase included the next 15 operations. It was observed that, with increasing experience, a statistically significant shortening in the average OT by about 25 min was achieved (p = 0.041). CONCLUSION: The LC phase for R-TAPP, for surgeon with previous experience in Lap TAPP, seems to be very quick without compromising the operative morbidity.

Prevalence of Thoracic Scoliosis in Adolescents in Turkey: Analysis of 1065 Chest Radiographs.

BACKGROUND: School scoliosis screening programs (SSSPs) are widely used for reporting the prevalence and improving the awareness of scoliosis. Thus, scoliosis could be prevented and/or treated in a timely manner. However, mild scoliosis (10°-20°) could be missed in SSSPs. Previously obtained plain chest radiographs could be used as an adjunct to SSSPs to detect the exact prevalence of scoliosis. In this study, we aimed to detect the prevalence of thoracic scoliosis in adolescents in Turkey using posteroanterior chest radiographs. METHODS: We conducted a cross-sectional radiologic study evaluating plain chest radiographs in adolescents who visited the emergency department or outpatient clinics at a community-based hospital. We also reviewed the literature regarding scoliosis screening in adolescents using the PubMed/MEDLINE search engine. RESULTS: We included 1065 adolescents. Thoracic scoliosis was detected on plain posteroanterior chest radiographs in 10.4% of the adolescents. The prevalence of thoracic scoliosis was significantly larger in females compared with males (12.3% vs. 8.6%; P = 0.047). We retrieved 140 articles regarding scoliosis screening in adolescents from the literature. Each continent had different scoliosis prevalence (according to Cobb angle ≥10° verified on a radiograph). CONCLUSIONS: SSSPs help detection of the prevalence of scoliosis and the factors associated with scoliosis in adolescents. However, patients with small-angle curves could be missed in SSSPs. Our results showed that plain posteroanterior chest radiographs could be used as an adjunct to SSSPs to accurately detect prevalence of scoliosis in adolescents.