Peripheral-central network analysis of cancer cachexia status accompanied by the polarization of hypothalamic microglia with low expression of inhibitory immune checkpoint receptors.

While the excessive inflammation in cancer cachexia is well-known to be induced by the overproduction of inflammatory mediators in the periphery, microflora disruption and brain dysfunction are also considered to contribute to the induction of cancer cachexia. Hypothalamic microglia play a crucial role in brain inflammation and central-peripheral immune circuits via the production of inflammatory mediators. In the present study, we evaluated possible changes in excessive secretion of gut microbiota-derived endotoxin and the expression timeline of several inflammation-regulatory mediators and their inhibiting modulators in hypothalamic microglia of a mouse model of cancer cachexia following transplantation of pancreatic cancer cells. We demonstrated that the plasma level of lipopolysaccharide (LPS) was significantly increased with an increase in anaerobic bacteria, especially Firmicutes, in the gut at the late stage of tumor-bearing mice that exhibited dramatic appetite loss, sarcopenia and severe peripheral immune suppression. At the early stage, in which tumor-bearing mice had not yet displayed "cachexia symptoms", the mRNA expression of pro-inflammatory cytokines, but not of the neurodegenerative and severe inflammatory modulator lipocalin-2 (LCN2), was significantly increased, whereas at the late "cachexia stage", the level of LCN2 mRNA was significantly increased along with significant decreases in levels of inhibitory immune checkpoint receptors programmed death receptor-1 (PD-1) and CD112R in hypothalamic microglia. In addition, a high density of activated neurons in the paraventricular nucleus (PVN) of the hypothalamus region and a significant increase in corticosterone secretion were found in cachexia model mice. Related to the cachexia state, released corticosterone was clearly increased in normal mice with specific activation of PVN neurons. A marked decrease in the natural killer cell population was also observed in the spleen of mice with robust activation of PVN neurons as well as mice with cancer cachexia. On the other hand, in vivo administration of LPS in normal mice induced hypothalamic microglia with low expression of inhibitory immune checkpoint receptors. These findings suggest that the induction of cancer cachexia may parallel exacerbation of the hypothalamic inflammatory status with polarization to microglia expressed with low levels of inhibitory immune checkpoint receptors following LPS release from the gut microflora.

The Accuracy of Guided Implant Surgery With Different Fields of View of Cone-Beam Computerized Tomography.

Although a smaller size field of view (FOV) of cone-beam computerized tomography (CBCT) reduces radiation exposure, its effect on the accuracy of static computer-aided implant surgery (s-CAIS) remains unknown. This study aimed to evaluate the impact of the size of FOV on the accuracy of s-CAIS and to investigate if the arch affects this effect. A total of 32 implant sites on 8 identical scannable models (maxillae and mandibles) were randomly allocated to 2 FOV sizes: test (5 × 5 cm) and control (10 × 10 cm). All models were scanned with an intraoral scanner (IOS). With the registration of the surface scan and CBCT image, a prosthetic-driven implant position was planned. Following the fabrication of surgical templates, a single-blinded surgeon placed all implants with the fully guided s-CAIS protocol. IOS captured the implant positions with the scan body attached. Implant-planning software measured the angular deviation, 3-dimensional (3D) deviation at the crest, and 3D deviation at the apex between preplanned and actual implant positions. Two-way analysis of variance was used to analyze the effect of FOV and arch on the deviations. The size of FOV did not show a significant effect (P > .198) on angular deviation, 3D deviation at the crest, or 3D deviation at the apex. No significant difference was found when comparing the effect of the size of FOV between the maxillary and mandibular implants. In conclusion, the use of small FOV CBCT demonstrated comparable accuracy of s-CAIS to the use of medium FOV CBCT.

Image Quality and Radiation Dose of Conventional and Wide-Field High-Resolution Cone-Beam Computed Tomography for Cerebral Angiography: A Phantom Study.

There has been an increase in the use of interventional neuroradiology procedures because of their non-invasiveness compared to surgeries and the improved image quality of fluoroscopy, digital subtraction angiography, and rotational angiography. Although cone-beam computed tomography (CBCT) images are inferior to multi-detector CT images in terms of low-contrast detectability and lower radiation doses, CBCT scans are frequently performed because of their accessibility. This study aimed to evaluate the image quality and radiation dose of two different high-resolution CBCTs (HR CBCT): conventional (C-HR CBCT) and wide-field HR CBCT (W-HR CBCT). The modulation transfer function (MTF), noise power spectrum (NPS), and contrast-to-noise ratio (CNR) were used to evaluate the image quality. On comparing the MTF of C-HR CBCT with a 256 × 256 matrix and that of W-HR CBCT with a 384 × 384 matrix, the MTF of W-HR CBCT with the 384 × 384 matrix was larger. A comparison of the NPS and CNR of C-HR CBCT with a 256 × 256 matrix and W-HR CBCT with a 384 × 384 matrix showed that both values were comparable. The reference air kerma values were equal for C-HR CBCT and W-HR CBCT; however, the value of the kerma area product was 1.44 times higher for W-HR CBCT compared to C-HR CBCT. The W-HR CBCT allowed for improved spatial resolution while maintaining the image noise and low-contrast detectability by changing the number of image matrices from 256 × 256 to 384 × 384. Our study revealed the image characteristics and radiation dose of W-HR CBCT. Given its advantages of low-contrast detectability and wide-area imaging with high spatial resolution, W-HR CBCT may be useful in interventional neuroradiology for acute ischemic stroke.

Delayed Right Ventricular Pacemaker Lead Perforation 9 Years After Implantation.

BACKGROUND Cardiac perforation is a rare complication of cardiac implantable electronic devices, with a reported incidence ranging from 0.1% to 5.2%. Delayed perforation, defined as perforation occurring more than 1 month after implantation, is more uncommon. In this report, we present a case of cardiac perforation involving the right ventricle wall that occurred 9 years after pacemaker implantation. CASE REPORT A 79-year-old woman presented with symptoms of dyspnea and was subsequently admitted to a hospital. She had undergone pacemaker implantation for a complete atrioventricular block 9 years prior to the presentation. The patient had right ventricular failure to capture and a resultant complete atrioventricular block. Computed tomography imaging revealed that the right ventricular lead had clearly protruded outside the heart; however, no pericardial effusion was observed. When the patient underwent open surgical repair, the ventricular tined lead was noted to be traversing the right ventricular apex. Device interrogation revealed a sudden increase followed by a gradual decrease in the right ventricular pacing threshold over the course of 2 months, indicating that the lead had slowly traversed the right ventricular muscle before ultimately rupturing through it. CONCLUSIONS This study described the case of a delayed right ventricular pacemaker lead perforation that occurred 9 years after implantation, which was managed via open surgical repair.

Periodontal Regeneration with Amnion-Chorion Membrane on Root Surface: A Retrospective Case Series.

This retrospective case series investigated the clinical and radiographic outcomes in 19 intrabony defects treated with periodontal regenerative therapy utilizing a combined approach. Placing an amnion-chorion membrane (ACM) as a biologic modifier on the root surface of the periodontally diseased tooth, combined with bone substitutes and an additional ACM as a barrier membrane, the treated sites were examined 8 to 24 months after the therapy. The preoperative (baseline) mean probing pocket depth (PPD) was 7.21 ± 1.08 mm, and the mean clinical attachment level (CAL) was 7.68 ± 1.49 mm. A mean PPD reduction of 4.05 ± 1.22 mm, CAL gain of 3.68 ± 1.34 mm, and 73.91% ± 22.02% of bone fill were recorded postoperatively. Without any adverse events, root-surface application of ACM as a biologic material in periodontal regenerative therapy could be a safe and cost-effective approach.

Elucidation of the mechanisms of exercise-induced hypoalgesia and pain prolongation due to physical stress and the restriction of movement.

Persistent pain signals cause brain dysfunction and can further prolong pain. In addition, the physical restriction of movement (e.g., by a cast) can cause stress and prolong pain. Recently, it has been recognized that exercise therapy including rehabilitation is effective for alleviating chronic pain. On the other hand, physical stress and the restriction of movement can prolong pain. In this review, we discuss the neural circuits involved in the control of pain prolongation and the mechanisms of exercise-induced hypoalgesia (EIH). We also discuss the importance of the mesolimbic dopaminergic network in these phenomena.

Clinical Evaluation of the Combination of rhPDGF-BB and Xenogeneic Bone Substitutes for Treatment of Severe Periodontal Intrabony Defects: A Case Series.

Growth factors are considered an important component for periodontal wound healing and a key element in the periodontal regeneration triad. Randomized controlled clinical trials have demonstrated that purified recombinant human platelet-derived growth factor-BB (rhPDGF-BB) in combination with bone graft materials is effective in treating intrabony periodontal defects. Many clinicians are currently using rhPDGF-BB in combination with xenogeneic or allogeneic bone. Therefore, the purpose of this case series was to assess the clinical effectiveness of combining rhPDGF-BB with xenogeneic bone substitutes to treat severe intrabony periodontal defects. Three patients with challenging deep and wide intrabony defects were treated using a combination of rhPDGF-BB and xenogeneic graft matrix. Probing depth (PD) reduction, bleeding on probing (BOP), mobility reduction, and radiographic bone fill (RBF) were observed for 12 to 18 months. PD decreased from 9 mm to 4 mm, BOP was eliminated, mobility decreased, and RBF ranged from 85% to 95% over the postsurgical observation period. These results indicate that combination of rhPDGF-BB with xenogeneic bone substitutes is a safe and effective graft that leads to favorable clinical and radiographic outcomes for treating severe intrabony periodontal defects. Larger case series or randomized studies will further elucidate the clinical predictability of this treatment protocol. Int J Periodontics Restorative Dent 2023;43:193-200. doi: 1011607/prd.6313.

Comparison of In Vitro Biofilm Formation on Titanium and Zirconia Implants.

Background: Peri-implant diseases are emerging issues in contemporary implant dentistry. As biofilms play a critical role in peri-implant diseases, the characteristic of resisting bacterial adhesion would be ideal for dental implants. The aims of the study were to compare titanium (Ti) and zirconia (Zr) implants regarding the amount of biofilm formation at different time frames and assess the distribution of biofilm on different aspects of dental implants. Methods: Biofilm was developed on Ti and Zr dental implants with a peri-implant-related multispecies model with Streptococcus oralis, Actinomyces naeslundii, Veillonella dispar, and Porphyromonas gingivalis, for 3 and 14 days. Quantitative assessment was performed with the measurement of total bacterial viability (colony forming units, CFU/mg). Scanning electron microscopy (SEM) was used to evaluate biofilm formation on different aspects of the implants. Results: Three-day-old biofilm on Ti implants was significantly higher than that on Zr implants (p < 0.001). The Ti and Zr groups were not significantly different for 14-day-old biofilm. SEM images demonstrated that 3-day-old biofilm on Zr implants was sparse while biofilm growth was more pronounced for 3-day-old biofilm on Ti implants and 14-day-old biofilm groups. It appeared that less biofilm formed on the valley compared to the thread top for 3-day-old biofilm on Zr implants. Differences between the valley and the thread top became indistinguishable with the development of mature biofilm. Conclusion: While early formed biofilms show greater accumulation on Ti implants compared to Zr implants, older biofilms between the two groups are comparable. The distribution of biofilms was not uniform on different areas of implant threads during early biofilm development.

The Effects of Clockwise and Counterclockwise Conventional and Osseodensification Drilling on the Dimensions, Density, and Biomechanical Properties of Bone.

Purpose: To compare the effects of regular implant drills to osseodensifying drills used in clockwise and counterclockwise motions on bone dimension change and primary implant stability. Materials and Methods: A total of 40 bone models were made (20 × 15 × 4 mm) from porcine tibia to represent implants placed in soft bone. Implant osteotomies were prepared in the bone models using one of the following techniques: (1) regular implant drills in a clockwise direction (group A), (2) regular implant drills in a counterclockwise direction (group B), (3) osseodensifying drills in a clockwise direction (group C), and (4) osseodensifying drills in a counterclockwise direction (group D). Bone-level tapered titanium alloy implants (4.1 × 10 mm) were placed following osteotomy creation. The implant stability quotient (ISQ) was measured after implant placement. Each bone model was scanned with an optical scanner to convert to Standard Tessellation Language (STL) files before and after the osteotomy creation. Presurgical and postsurgical STL files were superimposed, and the dimensional changes were measured at 1, 3, and 7 mm from the crestal bone. Histomorphometric analysis was done, and bone-to-implant contact percentage (BIC%) was calculated. Results: There were no significant differences in ISQ values (P = .239) between any of the groups. Histomorphometric analysis showed implants in group D had significantly higher BIC% than groups A (P = .020) and B (P = .009). The amount of bone expansion decreased with distance from the crest (P < .001). Groups B (P = .039) and D (P = .001) showed significant expansions at all levels compared with group A. No other statistically significant differences in dimensional change were found between groups. Conclusion: Both regular and osseodensification burs used in a counterclockwise motion contribute to expansion of bone dimension compared to conventional drilling methods.

Repeated activation of Trpv1-positive sensory neurons facilitates tumor growth associated with changes in tumor-infiltrating immune cells.

It is considered that sensory neurons extend into the tumor microenvironment (TME), which could be associated with tumor growth. However, little is known about how sensory signaling could promote tumor progression. In this study, chemogenetic activation of transient receptor potential vanilloid 1 (Trpv1)-positive sensory neurons (C-fibers) by the microinjection of AAV-hSyn-FLEX-hM3Dq-mCherry into the sciatic nerve dramatically increased tumor volume in tumor-bearing Trpv1-Cre mice. This activation in Trpv1::hM3Dq mice that had undergone tumor transplantation significantly reduced the population of tumor-infiltrating CD4+ T cells and increased the mRNA level of the M2-macrophage marker, CX3C motif chemokine receptor 1 (Cx3cr1) in immunosuppressive cells, such as tumor-associated macrophages (TAMs) and tumor-infiltrating monocytic myeloid-derived suppressor cells (M-MDSCs). Under these conditions, we found a significant correlation between the decreased expression of the M1-macrophage marker Tnf and tumor volume. These findings suggest that repeated activation of Trpv1-positive sensory neurons may facilitate tumor growth along with changes in tumor-infiltrating immune cells.

Elucidation of the mechanisms underlying tumor aggravation by the activation of stress-related neurons in the paraventricular nucleus of the hypothalamus.

A growing body of evidence suggests that excess stress could aggravate tumor progression. The paraventricular nucleus (PVN) of the hypothalamus plays an important role in the adaptation to stress because the hypothalamic-pituitary-adrenal (HPA) axis can be activated by inducing the release of corticotropin-releasing hormone (CRH) from the PVN. In this study, we used pharmacogenetic techniques to investigate whether concomitant activation of CRHPVN neurons could directly contribute to tumor progression. Tumor growth was significantly promoted by repeated activation of CRHPVN neurons, which was followed by an increase in the plasma levels of corticosterone. Consistent with these results, chronic administration of glucocorticoids induced tumor progression. Under the concomitant activation of CRHPVN neurons, the number of cytotoxic CD8+ T cells in the tumor microenvironment was dramatically decreased, and the mRNA expression levels of hypoxia inducible factor 1 subunit α (HIF1α), glucocorticoid receptor (GR) and Tsc22d3 were upregulated in inhibitory lymphocytes, tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs). Furthermore, the mRNA levels of various kinds of driver molecules related to tumor progression and tumor metastasis were prominently elevated in cancer cells by concomitant activation of CRHPVN neurons. These findings suggest that repeated activation of the PVN-CRHergic system may aggravate tumor growth through a central-peripheral-associated tumor immune system.

Cancer aggravation due to persistent pain signals with the increased expression of pain-related mediators in sensory neurons of tumor-bearing mice.

A growing body of evidence suggests that intractable pain reduces both the quality of life and survival in cancer patients. In the present study, we evaluated whether chronic pain stimuli could directly affect cancer pathology using tumor-bearing mice. For this purpose, we used two different models of chronic pain in mice, neuropathic pain and persistent postsurgical pain, with Lewis lung carcinoma (LLC) as tumor cells. We found that tumor growth was dramatically promoted in these pain models. As well as these pain models, tumor growth of LLC, severe osteosarcoma (AXT) and B16 melanoma cells was significantly promoted by concomitant activation of sensory neurons in AAV6-hM3Dq-injected mice treated with the designer drug clozapine-N-oxide (CNO). Significant increases in mRNA levels of vascular endothelial growth factor-A (Vegfa), tachykinin precursor 1 (Tac1) and calcitonin-related polypeptide alpha (Calca) in the ipsilateral side of dorsal root ganglion of AAV6-hM3Dq-injected mice were observed by concomitant activation of sensory neurons due to CNO administration. Moreover, in a model of bone cancer pain in which mice were implanted with AXT cells into the right femoral bone marrow cavity, the survival period was significantly prolonged by repeated inhibition of sensory neurons of AAV6-hM4Di-injected mice by CNO administration. These findings suggest that persistent pain signals may promote tumor growth by the increased expression of sensory-located peptides and growth factors, and controlling cancer pain may prolong cancer survival.

Highly Metastatic Subpopulation of TNBC Cells Has Limited Iron Metabolism and Is a Target of Iron Chelators.

Excess iron is known to be a risk factor of carcinogenesis. Although iron chelators show anti-cancer effects, they have not been used successfully to treat cancer patients. Triple-negative breast cancer (TNBC) is a disease with poor prognosis without effective treatments. Thus, we aimed to evaluate a possibility of iron chelators as a therapy for TNBC. Deferasirox (DFX), an iron chelator, suppressed the growth of 4T1 murine TNBC cell line cells in vitro and in vivo. Lung metastasis was further significantly reduced, leading to the hypothesis that iron metabolism between metastatic and non-metastatic cells may be different. An analysis of existing database demonstrated that the expression of iron-uptake genes was significantly suppressed in TNBC cells that metastasized to lymph nodes or lungs compared to those in primary tumors. A highly metastatic clone of the murine 4T1 TNBC cells (4T1-HM) did not proliferate well under iron-rich or iron-depleted conditions by iron chelators compared to a low-metastatic clone (4T1-LM). Bulk RNA-seq analysis of RNA from 4T1-HM and 4T1-LM cells suggested that the PI3K-AKT pathway might be responsible for this difference. Indeed, DFX suppressed the proliferation via the AKT-mTOR pathway in 4T1-HM and the human MDA-MB-231 cells, a human mesenchymal-like TNBC cell line. DFX also suppressed the growth of 4T1-HM tumors in comparison to 4T1-LM tumors, and reduced lung metastases after surgical resection of primary 4T1 tumors. These results indicated, for the first time, that highly metastatic TNBC cells have limited iron metabolism, and they can be more effectively targeted by iron chelators.

Histologic and Histomorphometric Analyses of Peri-implant Bone from Loaded Dental Implants: A Case Report

The histological findings and histomorphometrical analyses of peri-implant tissues from nine functionally loaded dental implants from an adult cadaver were analyzed. Despite the presence of peri-implant bone loss, all implants were found to have a high degree of osseointegration, with the bone-implant contact (BIC) ranging from 69% to 88%. The mean value of the BIC was 83.2 ± 4.3% (range: 76.5 - 87.7%) for the maxillary implants and 74.4 ± 7.1% (range: 69.4 - 84.9%) for the mandibular implants. The BIC was comparable for maxillary and mandibular implants. Relatively prominent bone remodeling and resorption with soft tissue ingrowth were observed in the vertical bony defects compared to the areas without intrabony components, which might represent the sequence of bone loss around the dental implants.

The effect of systemic antibiotics on periodontal regeneration: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: The aim of this systematic review and meta-analysis was to evaluate the clinical efficacy of the use of systemic antibiotics in regenerative periodontal surgery for treating teeth affected by periodontitis. DATA SOURCES: Electronic (MEDLINE, EMBASE, LILACS, Scopus, and Cochrane) and manual literature searches for human randomized controlled trial studies published up to November 2022 were conducted by two reviewers. Meta-analysis was performed to assess probing pocket depth (PPD) reduction and clinical attachment level (CAL) gain in groups receiving systemic antibiotics compared to those not receiving systemic antibiotics. A total of eight studies were included. While treated sites were intrabony defects in six papers, two studies focused on furcation defects. For intrabony defects, the weighted mean difference (WMD) of 0.30 mm (95% CI -0.18 to 0.78) and 0.27 mm (95% CI -0.13 to 0.66) was calculated for PPD reduction and CAL gain, respectively. The differences between antibiotics and non-antibiotics groups for PPD and CAL were not statistically significant. Quantitative analysis could not be performed for furcation defects due to the limited number of studies. However, regardless of the membrane type selection, the existing evidence indicated that antibiotics did not lead to superior clinical outcomes for furcation defects at 9 to 12 months after the regenerative procedures. CONCLUSION: Based on this meta-analysis study's findings, the use of adjunct systemic antibiotics in regenerative periodontal surgery did not appear to achieve more favorable clinical outcomes. Thus, the use of adjunct systemic antibiotics as part of the regenerative periodontal therapy might not be justifiable and should be reconsidered. (Quintessence Int 2023;54:210-219; doi: 10.3290/j.qi.b3648957).

Evaluation of the accuracy of buccal bone thickness measurement from cone beam computed tomography compared with histologic analysis.

STATEMENT OF PROBLEM: Three-dimensional radiographic assessment of buccal bone thickness and its integrity from cone beam computed tomography (CBCT) plays an essential role in immediate implant placement. However, the accuracy of CBCT measurements for the assessment of buccal bone thickness adjacent to maxillary anterior teeth is not well understood. PURPOSE: The purpose of this observational study was to evaluate the accuracy of measuring the buccal bone thickness of maxillary anterior teeth from CBCT compared with direct measurement from histologic sections. A secondary objective was to analyze whether a minimal level of buccal bone thickness of maxillary anterior teeth can be detected from the CBCT scan. MATERIAL AND METHODS: Five embalmed human cadavers with a complete anterior dentition were included in this study, providing 30 teeth for evaluation. After preparing reference notches at the gingival margin of each tooth, the anterior segments were scanned. The buccal bone thickness at 3, 5, and 7 mm from the notches was measured on the cross-sections obtained from the CBCT and histomorphometric images for a total of 90 sites. The CBCT measurements were compared with the histomorphometric measurements, and their agreement was assessed by using the Bland-Altman plots and intraclass correlation coefficients. The sensitivity and specificity of buccal bone detection were calculated from the CBCT scan. RESULTS: Histologic examination showed absence of the buccal bone in 29 sites (32%). The mean ±standard deviation thickness of the buccal bone was 0.52 ±0.05 mm (range: 0 to 1.97 mm) from the CBCT analysis and 0.40 ±0.05 mm (range: 0 to 1.67 mm) from histology. Measurements obtained from the CBCT sections significantly overestimated the buccal bone thickness when compared with the histologic evaluation (P=.001). The intraclass correlation coefficient of buccal bone thickness between the CBCT and histology was ≤0.53, an agreement considered as poor. The sensitivity of the CBCT as a diagnostic tool to detect the presence or absence of the buccal bone was 75.4%, and the specificity was 65.5%. CONCLUSIONS: The buccal bone thickness of maxillary anterior teeth was less than 2 mm at all sites as measured with both CBCT and histology evaluations. CBCT measurements had relatively low accuracy and reliability for the measurement of buccal bone thickness. These findings should be considered when using CBCT as a measuring tool for thin bone structures.

Successful trans-femoral retrieval of a stuck axillary Impella 5.0 device.

We describe a case in which an axillary Impella 5.0, stuck in an area of calcification in the right subclavian artery, could not be retrieved in the usual manner. However, it was successfully removed using a long 22-Fr sheath and snaring catheter by means of the trans-femoral artery. Device retrieval using the trans-femoral artery snare technique is considered a valid option for removing the Impella device in patients who exhibit this complication.

Possible mechanism for improving the endogenous immune system through the blockade of peripheral µ-opioid receptors by treatment with naldemedine.

BACKGROUND: It has been considered that activation of peripheral µ-opioid receptors (MORs) induces side effects of opioids. In this study, we investigated the possible improvement of the immune system in tumour-bearing mice by systemic administration of the peripheral MOR antagonist naldemedine. METHODS: The inhibitory effect of naldemedine on MOR-mediated signalling was tested by cAMP inhibition and ß-arrestin recruitment assays using cultured cells. We assessed possible changes in tumour progression and the number of splenic lymphocytes in tumour-bearing mice under the repeated oral administration of naldemedine. RESULTS: Treatment with naldemedine produced a dose-dependent inhibition of both the decrease in the cAMP level and the increase in ß-arrestin recruitment induced by the MOR agonists. Repeated treatment with naldemedine at a dose that reversed the morphine-induced inhibition of gastrointestinal transport, but not antinociception, significantly decreased tumour volume and prolonged survival in tumour-transplanted mice. Naldemedine administration significantly decreased the increased expression of immune checkpoint-related genes and recovered the decreased level of toll-like receptor 4 in splenic lymphocytes in tumour-bearing mice. CONCLUSIONS: The blockade of peripheral MOR may induce an anti-tumour effect through the recovery of T-cell exhaustion and promotion of the tumour-killing system.

Investigating the Effects of Dehydrated Human Amnion-Chorion Membrane on Periodontal Healing.

Each growth factor (GF) has different effects and targets, and plays a critical role in periodontal healing. Dehydrated human amnion-chorion membrane (dHACM) contains various GFs and has been used to enhance wound healing. The purpose of this study was to evaluate the effects of dHACM on periodontal healing, using in vitro and in vivo experimental approaches. Standardized periodontal defects were created in rats. The defects were randomly divided into three groups: Unfilled, filled with hydroxypropyl cellulose (HPC), and dHACM+HPC. At 2 and 4 weeks postoperatively, periodontal healing was analyzed by microcomputed tomography (micro-CT), and histological and immunohistochemical analyses. In vitro, periodontal ligament-derived cells (PDLCs) isolated from rat incisors were incubated with dHACM extract. Cell proliferation and migration were evaluated by WST-1 and wound healing assay. In vivo, micro-CT examination at 2 weeks revealed enhanced formation of new bone in the dHACM+HPC group. At 4 weeks, the proportions of vascular endothelial growth factor (VEGF)-positive cells and α-smooth muscle actin (α-SMA)-positive blood vessels in the dHACM+HPC group were significantly greater than those in the Unfilled group. In vitro, dHACM extracts at 100 µg/mL significantly increased cell proliferation and migration compared with control. These findings suggest that GFs contained in dHACM promote proliferation and migration of PDLCs and angiogenesis, which lead to enhanced periodontal healing.

Successful heart transplantation in a patient with adolescent-onset dilated cardiomyopathy secondary to propionic acidaemia: a case report.

Background: Propionic acidaemia (PA) is an autosomal recessive disorder resulting from deficiency of propionyl-CoA carboxylase, a mitochondrial enzyme that metabolizes propionyl-CoA. Generally, patients with PA develop symptoms in the neonatal period due to protein intake through breastfeeding; however, late-onset PA with atypical symptoms, including cardiomyopathy, has been recently reported. Case summary: We present the case of a 25-year-old male with late-onset PA complicated by advanced heart failure (HF) due to isolated secondary dilated cardiomyopathy, who required left ventricular assist device (LVAD) implantation and finally underwent heart transplantation (HTx). Initially, the patient developed HF at the age of 16 and was diagnosed with mitochondrial cardiomyopathy. Due to refractory HF, he underwent an LVAD implantation and was scheduled for HTx. During the preoperative period for HTx, the patient suffered from sepsis due to the worsening of LVAD driveline exit-site infection complicated by overt metabolic acidosis, finally leading to the diagnosis of late-onset PA. After this diagnosis, adequate nutritional interventions were introduced, and the cardiac function was partially restored enough for him to be weaned-off LVAD; however, the patient became inotrope dependent and underwent HTx. The post-HTx course was uneventful with special nutritional management, and he has experienced no adverse metabolic events in the past 3 years. Discussion: Late-onset PA can cause isolated adult-onset cardiomyopathy, and LVAD or HTx should be considered when PA is complicated by advanced HF and is unresponsive to conventional medical therapies.