Notes

PID: A good integrative and also thorough program associated with place intron.
Cervical sagittal balance plays important roles in transmitting the load of the head and maintaining global spinal balance. This study aimed to identify the association of cervical sagittal alignment with adjacent segment degeneration (ASD) and heterotopic ossification (HO) after Prestige-LP cervical disc replacement (CDR).

We enrolled 132 patients who underwent one-level Prestige-LP CDR with 2-10 years of follow-up. Cinchocaine mouse Cervical sagittal alignment parameters, including the degree of C2-C7 lordosis (CL), functional spinal unit angle (FSUA), sagittal vertical axis (SVA),, and T1 slope (T1s), were measured. ASD and HO were evaluated at the last follow-up. Unpaired
tests and logistic regression analysis were used to identify the associations of cervical sagittal alignment with ASD and HO.

We found that patients who developed ASD showed significantly lower FSUA (2.1° vs. -1.4°,
< 0.001) and T1s values (28.4° vs. 25.5°,
= 0.029) after surgery. Similarly, the postoperative CL was significantly better in patients without ASD or HO (18.0° vs. 14.4°,
= 0.043). The decrease in the T1s at the last follow-up was significantly larger in the patients with ASD (-11.0° vs. -3.2°,
= 0.003), HO (-6.7° vs. -2.7°,
= 0.050), and ASD or HO (-7.0° vs. -0.8°,
< 0.001) than in those without ASD or HO. Multivariate logistic regression analysis showed that both the FSUA and T1s are associated with ASD and that the degree of CL is associated with postoperative complications.

The results imply that maintaining cervical sagittal alignment after Prestige-LP CDR is important.
The results imply that maintaining cervical sagittal alignment after Prestige-LP CDR is important.Ovarian cancer is the most lethal of gynecological cancers with 5-year survival rate of ca. 45%. The most common histologic subtype is high-grade serous carcinoma, which typically is presented with advanced stage and development of chemoresistance. Therefore, new treatment options, including immunotherapies, are needed. Understanding the features of the immune cell populations in the tumor microenvironment is essential for developing personalized treatments and finding predictive biomarkers. Digital image analysis may enhance the accuracy and reliability of immune cell infiltration assessment in the tumor microenvironment. The aim of this study was to characterize tumor microenvironment in a retrospective cohort of high-grade serous carcinoma samples with whole-slide imaging and digital image analysis. Formalin-fixed paraffin-embedded high-grade serous carcinoma tumor tissue samples (n = 67) were analyzed for six immunohistochemical stainings CD4, CD8, FoxP3, granzyme B, CD68, and CD163. The stained sample slcombined positivity of CD8 and granzyme B warrants further investigation with respect to predicting response to immune therapy. Neoadjuvant chemotherapy may have an effect on the tumor microenvironment and therefore on the response to immuno-oncologic or chemotherapy treatments.We treated a 25-year-old male sickle cell disease (SCD) patient with a long-standing wound of the lower limb with radiologically confirmed osteomyelitis of the tibia, successfully managed by multimodality treatment. Culture of the wound after sequestrectomy revealed a Staphylococcus aureus infection, which was treated with appropriate antibiotics as per culture and sensitivity results. The patient had been under treatment for the same since 3 years in his home country with no improvement. He had a history of a leg ulcer due to injury and as is common in SCD patients, the ulcer led to bone infection. He had taken long courses of antibiotics and surgical drainage of pus, which are the usual treatment modalities used in such patients, with extended periods to healing and long durations of pain and tenderness. In this case systemic antibiotics were used only for 7 days. Low-molecular-weight heparin and dextran, negative pressure wound therapy coupled with nano silver dressings and hyperbaric oxygen treatment for 15 days led to the patient being pain free within 10 days of instituting treatment. The patient healed completely after 1 year and has been incident free since the past 10 years. In essence, this case has shown that multi-modality treatment may lead to faster wound closure and reduction in pain in SCD patients suffering from osteomyelitis.It is well-documented that lead (Pb) toxicity can affect almost all systems in living organisms. It can induce selective autophagy of mitochondria (mitophagy) by triggering reactive oxygen species production. Emerging evidence has suggested that Pb-induced autophagy can also be activated by the endoplasmic reticulum (ER) stress pathway. However, the interplay between ER stress and mitophagy remains to be elucidated. In this study, human embryonic kidney HEK293 cells were employed to investigate the role of ER stress in Pb-induced mitophagy. The results showed that the cell viability was decreased and cell damage was induced after exposure to Pb (0, 0.5, 1, 2, and 4 mM) for 24 h in a dose-dependent manner. Moreover, the expression of LC3-Ⅱ was significantly increased, and the expression of HSP60 was dramatically decreased after exposure to 1 mM and 2 mM Pb, indicating the induction of mitophagy following Pb exposure. Meanwhile, the expressions of activating transcription factor 6, inositol-requiring protein-1α, CCAAT/enhancer binding protein homologous protein, and glucose-regulated protein 78 were dramatically increased after Pb treatment, signifying the initiation of ER stress. Notably, the mitophagic effect was significantly compromised when ER stress was inhibited by 0.5 mM 4-phenylbutyrate, which was evidenced by lesser decreases in HSP60 expression and level of LC3-Ⅱ, suggesting Pb-induced mitophagy may be activated by the ER stress. Taken together, these findings provide a better understanding of Pb toxicity and suggest that Pb-induced ER stress may play a regulatory role in the upstream of mitophagy.Chronic low back pain (cLBP) that cannot be attributable to a specific pathoanatomical change is associated with high personal and societal costs. Still, the underlying mechanism that causes and sustains such a phenotype is largely unknown. Emerging evidence suggests that epigenetic changes play a role in chronic pain conditions. Using reduced representation bisulfite sequencing (RRBS), we evaluated DNA methylation profiles of adults with non-specific cLBP (n = 50) and pain-free controls (n = 48). We identified 28,325 hypermethylated and 36,936 hypomethylated CpG sites (p  10%), the majority of which were located in CpG island (50%) and promoter regions (48%) on the associated genes. The genes associated with the differentially methylated regions were highly enriched in biological processes that have previously been implicated in immune signaling, endochondral ossification, and G-protein coupled transmissions. Our findings support inflammatory alterations and the role of bone maturation in cLBP. This study suggests that epigenetic regulation has an important role in the pathophysiology of non-specific cLBP and a basis for future studies in biomarker development and targeted interventions.
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