Corrigendum: Correlation between amygdala nuclei volumes and memory in cognitively normal adults carrying the ApoE ε3/ε3 allele.

[This corrects the article DOI: 10.3389/fnagi.2021.747288.].

Risk factors for ninety-day readmission following cervical surgery: a meta-analysis.

BACKGROUND: As an important evaluation index after cervical surgery, ninety-day readmission is gradually being valued. Our study collected the latest published relevant studies, analyzed the risk factors of ninety-day readmission after cervical surgery, and continuously improved the postoperative rehabilitation plan. This study focuses on two research hotspots: (1) What is the rate of ninety-day readmission after cervical surgery? (2) What are the risk factors affecting the ninety-day readmission? METHODS: Based on the Cochrane Library, PubMed, Web of Science, and Embase databases, this study searched for studies about ninety-day readmission after cervical surgery, from the establishment of the database to August 1, 2022. The evaluation indicators are as follows: age, American Society of Anesthesiology physical status (ASA) class, diabetes, hypertension, chronic heart diseases, chronic lung diseases, income, and payments for hospitalization. The meta-analysis was performed using Review Manager 5.4. RESULTS: Seven studies with 222,490 participants were eligible for our meta-analysis. The analysis displayed that there were statistically significant differences in the age (MD = - 4.60, 95%CI - 4.89-4.31, p < 0.001), diabetes (OR = 0.60, 95%CI 0.56-0.64, p < 0.00001), hypertension (OR = 0.40, 95%CI 0.30-0.54, p < 0.00001), chronic heart diseases (OR = 0.05, 95%CI 0.01-0.19, p < 0.00001), chronic lung diseases (OR = 0.46, 95%CI 0.43-0.49, p < 0.00001), income (OR = 2.85, 95%CI 1.82-4.46, p < 0.00001), and payments for hospitalization (OR = 2.29, 95%CI 1.14-4.59, p = 0.02) between readmission and no readmission groups. In terms of the ASA, there was no difference on the ninety-day readmission (p = 0.78). CONCLUSION: Age, diabetes, hypertension, chronic heart diseases, chronic lung diseases, income, and payments for hospitalization are the risk factors of ninety-day readmission following cervical surgery.

Targeted Delivery of Immunostimulatory CpG Oligodeoxynucleotides to Antigen-Presenting Cells in Draining Lymph Nodes by Stearic Acid Modification and Nanostructurization.

Polypod-like structured nucleic acids (polypodnas), which are nanostructured DNAs, are useful for delivering cytosine-phosphate guanine oligodeoxynucleotides (CpG ODNs) to antigen-presenting cells (APCs) expressing Toll-like receptor 9 (TLR9) for immune stimulation. Lipid modification is another approach to deliver ODNs to lymph nodes, where TLR9-positive APCs are abundant, by binding to serum albumin. The combination of these two methods can be useful for delivering CpG ODNs to lymph nodes in vivo. In the present study, CpG1668, a phosphodiester-type CpG ODN, was modified with stearic acid (SA) to obtain SA-CpG1668. Tripodna, a polypodna with three pods, was selected as the nanostructured DNA. Tripodnas loaded with CpG1668 or SA-CpG1668 were obtained in high yields. SA-CpG1668/tripodna bound more efficiently to plasma proteins than CpG1668/tripodna and was more efficiently taken up by macrophage-like RAW264.7 cells than CpG1668/tripodna, whereas the levels of tumor necrosis factor-α released from the cells were comparable between the two. After subcutaneous injection into mice, SA-CpG1668/tripodna induced significantly higher interleukin (IL)-12 p40 production in the draining lymph nodes than SA-CpG1668 or CpG1668/tripodna, with reduced IL-6 levels in plasma. These results indicate that the combination of SA modification and nanostructurization is a useful approach for the targeted delivery of CpG ODNs to lymph nodes.

Correlation Between Amygdala Nuclei Volumes and Memory in Cognitively Normal Adults Carrying the ApoE ε3/ε3 Allele.

The amygdala is known to be related to cognitive function. In this study, we used an automated approach to segment the amygdala into nine nuclei and evaluated amygdala and nuclei volumetric changes across the adult lifespan in subjects carrying the apolipoprotein E (ApoE) ε3/ε3 allele, and we related those changes to memory function alteration. We found that except the left medial nucleus (Me), whose volume decreased in the old group compared with the middle-early group, all other nuclei volumes presented a significant decline in the old group compared with the young group. Left accessory basal nucleus (AB) and left cortico-amygdaloid transition area (CAT) volumes were also diminished in the middle-late group. In addition, immediate memory recall is impaired by the process of aging, whereas delayed recall and delayed recognition memory functions were not significantly changed. We found significant positive correlations between immediate recall scores and volumes of the bilateral basal nucleus (Ba), AB, anterior amygdaloid area (AAA), CAT, whole amygdala, left lateral nucleus (La), left paralaminar nucleus (PL), and right cortical nucleus (Co). The results suggest that immediate recall memory decline might be associated with volumetric reduction of the amygdala and its nuclei, and the left AB and left CAT might be considered as potential imaging biomarkers of memory decline in aging.

Enhanced Immunostimulatory Activity of CpG Oligodeoxynucleotide by the Combination of Mannose Modification and Incorporation into Nanostructured DNA.

The immunostimulatory activity of unmethylated cytosine-phosphate-guanine oligodeoxynucleotide (CpG ODN) could be improved via delivery to immune cells expressing Toll-like receptor 9 (TLR9). Previously, we showed that the polypod-like structured nucleic acid (polypodna), a nanostructured DNA comprised of three or more ODNs, was an efficient system for the delivery of CpG ODNs to immune cells. Because some TLR9-positive immune cells express mannose receptors (MR), the uptake of polypodna by immune cells can be further increased by its modification with mannose. In this study, we selected the phosphodiester CpG ODN, ODN1668, which has a sequence identical to CpG1668, and a hexapodna, a polypodna with six pods, to design a hexapodna that harbored ODN1668 or the mannosylated CpG ODN (Man-ODN1668) synthesized via modification of the 5'-terminal of ODN1668 with a synthesized mannose motif. By mixing ODN1668 or Man-ODN1668 with the hexapodna, ODN1668/hexapodna and Man-ODN1668/hexapodna were successfully formed with high yields. However, Man-ODN1668/hexapodna was found to induce a greater tumor necrosis factor-α release from TLR9- and MR-positive mouse peritoneal macrophages and macrophage-like J774.1 cells than Man-ODN1668 or ODN1668/hexapodna. These results indicate that the combination of mannose modification and incorporation into nanostructured DNA is a useful approach for enhancing the immunostimulatory activity of CpG ODN.

Construction of Monomeric and Dimeric G-Quadruplex-Structured CpG Oligodeoxynucleotides for Enhanced Uptake and Activation in TLR9-Positive Macrophages.

The G-quadruplex (GQ) structure has potential applications in nucleic acid drug delivery because of its superior stability. In this study, we added one G-tract (five guanines) to an unmethylated phosphodiester-linked cytosine-phosphate-guanine oligodeoxynucleotide (CpG ODN), a potential immune adjuvant, to construct a GQ-structured CpG ODN with precise structural properties, increased biological stability, and efficient delivery to Toll-like receptor 9 (TLR9)-positive immune cells. A G-tract was added to phosphodiester-backboned CpG1668 at the 5'-end [1668(5'-G5)], 3'-end [1668(3'-G5)], or within the sequence [1668(mid-G5)]. Circular dichroism analysis showed that all CpG ODNs with a G-tract formed parallel GQ structures, irrespective of its position. Electrophoresis showed that 1668(5'-G5) formed a GQ dimer, whereas others remained GQ monomers. GQ-structured CpG ODNs induced greater tumor necrosis factor-α and interleukin-6 secretion from TLR9-positive mouse macrophage-like RAW264.7 cells than single-stranded CpG ODNs, with the highest for 1668(3'-G5). GQ structuration increased CpG ODN uptake by RAW264.7 cells, and 1668(3'-G5) decomposed more slowly in serum than 1668(5'-G5). Thus, GQ formation with one G-tract is a simple and efficient strategy for CpG ODN delivery to TLR9-positive cells, and addition of a G-tract to the 3'-end is effective in obtaining monomeric GQ-structured CpG ODN with high biological stability and immunostimulatory activity.

Nanostructured DNA for the delivery of therapeutic agents.

DNA and RNA, the nucleic acids found in every living organism, are quite crucial, because not only do they store the genetic information, but also they are used as signals through interaction with various molecules within the body. The nature of nucleic acids, especially DNA, to form double-helix makes it possible to design nucleic acid-based nanostructures with various shapes. Because the shapes as well as the physicochemical properties determine their interaction with proteins or cells, nanostructured DNAs will have different features in the interaction compared with single- or double-stranded DNA. Some of these unique features of nanostructured DNA make ways for efficient delivery of therapeutic agents to specific targets. In this review, we begin with the factors affecting the properties of nanostructured DNA, followed by summarizing the methods for the development of nanostructured DNA. Further, we discuss the characteristics of nanostructured DNA and their applications for the delivery of bioactive compounds.

Numerical and Experimental Analyses on the Temperature Distribution in the Dental Implant Preparation Area when Using a Surgical Guide.

PURPOSE: During dental implantation, if the temperature within the bone tissue exceeds a critical value, the thermal necrosis of bone cells may take place, inhibiting osseointegration. In contrast to conventional dental implant surgery, a surgery guided by a surgical template is a safer and more efficient technique; however, the temperature within the implant field is more difficult to control, because the surgical guide blocks irrigation water. The purpose of this study was to investigate the temperature distribution in the drilling site when preparing for dental implant placement with a surgical guide, and to derive suggestions for clinical operation. MATERIALS AND METHODS: Initially, the sources of heat during drilling were investigated, and theoretical equations were listed. Subsequently, a measurement system using thermocouples was constructed, with which the temperature increments at specific points in the simulated bone samples were recorded during guided drilling with different cooling methods. Based on the equations and data assessed, a thermal simulation model with a finite element method (FEM) was created, and the temperature change of the whole surgical field was calculated on the basis of the numerical simulation results. Consequently, the point experiencing the highest temperature within the bone was determined. RESULTS: From the experimental measurements, the highest temperature increment was located at a depth of 6 mm without irrigation and at 8 mm with cooling, rather than at the deepest point of the prepared hole. Because the surgical guide blocks the cooling water from entering the drilling site, the biggest increment of temperature using conventional irrigation with the surgical guide was 1.95 times that recorded when using a surgical guide consisting of cooling channels, and 3.6 times that recorded using a drill with an internal cooling hole. And from numerical analysis, during drilling for implant placement site with conventional irrigation, the highest temperature (45.6°C) was close to the critical point at which bone necrosis occurs. CONCLUSIONS: Based on theoretical analysis, experimentation, and FEM simulation, the temperature distribution of the drilling area in the placement of dental implants under surgical guide was determined. For clinical operation, improved cooling methods, such as using a drill with an internal cooling channel, should be used, and the drill should be regularly withdrawn during drilling.

Buttressing Salicylaldehydes: A Multipurpose Directing Group for C(sp3 )-H Bond Activation.

A palladium-catalyzed reaction of primary amines with iodoarenes produces γ-arylated primary amines. A bulky salicylaldehyde, which is marked as easily available, installable, removable, and recoverable, plays a key role in directing palladium to site-selectively activate the C-H bond located γ to the amino group.

Synergistic Pd/enamine catalysis: a strategy for the C-H/C-H oxidative coupling of allylarenes with unactivated ketones.

By combining catalytic nucleophilic enamine activation with Pd-catalyzed C-H activation of allylarenes, the first oxidative allylic alkylation of unactivated ketones was achieved. Mechanistically, the Pd-catalyzed allylic C-H activation and proline-catalyzed ketone nucleophilic activation worked synergistically for the oxidative cross-coupling between allylarenes and unactivated ketones.

[The influence of drilling pulling ways and cooling systems on dental implant surgery].

PURPOSE: To study the effect of different ways of pulling the drilling burs and cooling systems on alveolar bone temperature of the surgical area, and explore the changes of temperature field in dental implants. METHODS: Forty-eight unified standard artificial (nylon) bone blocks were fabricated and divided into 6 groups according to different drilling pulling ways and cooling systems. The changes of bone temperature field were detected in 6 groups, and the highest temperature in temperature field was measured and recorded. The date was analyzed with SPSS 12.0 software package for ANOVA. RESULTS: The temperature in the surgical area using internal cooling systems under the same drilling pulling was lower than using external cooling systems. The temperature in the surgical area using secondary drilling pulling way was lower than using direct drilling methods under the same cooling systems. The temperature in the surgical area using secondary drilling pulling way was the lowest when internal cooling systems was adopted(P<0.05). CONCLUSIONS: Drilling pulling way and internal cooling systems can effectively reduce the temperature in the surgical area, lessen heat production and improve the success rate of dental implants.

Revealing the metal-like behavior of iodine: an iodide-catalysed radical oxidative alkenylation.

In this work, we have described an alternative alkenylation approach to illustrate the metal-like behaviour of iodine in cross-coupling reactions. Alkenylation could proceed through iodide catalysed radical initiation, radical addition and iodine promoted alkenyl functionality recovery. Catalytic HI elimination similar to the ß-hydride elimination of transition metals was realized for the radical alkenylation of sulfonyl hydrazides. Operando IR and cyclic voltammetry experiments were carried out to confirm the crucial role of iodine in the radical alkenylation process.