Enhanced in vitro type 1 conventional dendritic cell generation via the recruitment of hematopoietic stem cells and early progenitors by Kit ligand.

In vitro culture of bone marrow (BM) with Fms-like tyrosine kinase 3 ligand (Flt3L) is widely used to study development and function of type 1 conventional dendritic cells (cDC1). Hematopoietic stem cells (HSCs) and many progenitor populations that possess cDC1 potential in vivo do not express Flt3 and thus may not contribute to Flt3L-mediated cDC1 production in vitro. Here, we present a KitL/Flt3L protocol that recruits such HSCs and progenitors into the production of cDC1. Kit ligand (KitL) is used to expand HSCs and early progenitors lacking Flt3 expression into later stage where Flt3 is expressed. Following this initial KitL phase, a second Flt3L phase is used to support the final production of DCs. With this two-stage culture, we achieved approximately tenfold increased production of both cDC1 and cDC2 compared to Flt3L culture. cDC1 derived from this culture are similar to in vivo cDC1 in their dependence on IRF8, ability to produce IL-12, and induction of tumor regression in cDC1-deficient tumor-bearing mice. This KitL/Flt3L system for cDC1 production will be useful in further analysis of cDC1 that rely on in vitro generation from BM.

Developmental exposure to 17-α-hydroxyprogesterone caproate disrupts decision-making in adult female rats: A potential role for a dopaminergic mechanism.

The synthetic progestin, 17α-hydroxyprogesterone caproate (17-OHPC), is administered to pregnant individuals at risk for preterm birth and is likely transferred from mother to fetus. Yet, there is little information regarding the potential effects of 17-OHPC administration on behavioral and neural development in offspring. In rats, neonatal 17-OHPC exposure altered dopaminergic fiber distribution and density in the prelimbic medial prefrontal cortex (mPFC) in neonates and adolescents, respectively. Additionally, neonatal 17-OHPC exposure in male rats increased response omissions in a delay discounting task of impulsive decision-making. Because developmental 17-OHPC exposure has differential effects in males and females, investigating the effects of 17-OHPC on impulsive decision-making in female rats is necessary. The present study tested the effects of developmental 17-OHPC exposure (P1-P14) in a delay discounting task in which female rats chose between a small immediate reward and a larger delayed (0, 15 30, or 45 s) reward. 17-OHPC-exposed females made more omissions than controls. There was no effect of 17-OHPC on large reward preference nor on response time, and omissions were similar during both free- and forced-choice trials. The present study also aimed to investigate the neural mechanisms underlying omissions in 17-OHPC-exposed female rats. The dopamine transporter inhibitor, methylphenidate (MPH), was administered prior to delay discounting testing. MPH treatment did not reduce omissions in 17-OHPC-exposed females. If anything, MPH increased omissions in control females nearly fourfold during the longest delays. These results suggest that developmental 17-OHPC exposure increased omissions without affecting impulsivity or slowing decision-making. Furthermore, omissions may be regulated, at least in part, by dopaminergic mechanisms.

Induction of cancer neoantigens facilitates development of clinically relevant models for the study of pancreatic cancer immunobiology.

Neoantigen burden and CD8 T cell infiltrate are associated with clinical outcome in pancreatic ductal adenocarcinoma (PDAC). A shortcoming of many genetic models of PDAC is the lack of neoantigen burden and limited T cell infiltrate. The goal of the present study was to develop clinically relevant models of PDAC by inducing cancer neoantigens in KP2, a cell line derived from the KPC model of PDAC. KP2 was treated with oxaliplatin and olaparib (OXPARPi), and a resistant cell line was subsequently cloned to generate multiple genetically distinct cell lines (KP2-OXPARPi clones). Clones A and E are sensitive to immune checkpoint inhibition (ICI), exhibit relatively high T cell infiltration, and have significant upregulation of genes involved in antigen presentation, T cell differentiation, and chemokine signaling pathways. Clone B is resistant to ICI and is similar to the parental KP2 cell line in terms of relatively low T cell infiltration and no upregulation of genes involved in the pathways noted above. Tumor/normal exome sequencing and in silico neoantigen prediction confirms successful generation of cancer neoantigens in the KP2-OXPARPi clones and the relative lack of cancer neoantigens in the parental KP2 cell line. Neoantigen vaccine experiments demonstrate that a subset of candidate neoantigens are immunogenic and neoantigen synthetic long peptide vaccines can restrain Clone E tumor growth. Compared to existing models, the KP2-OXPARPi clones better capture the diverse immunobiology of human PDAC and may serve as models for future investigations in cancer immunotherapies and strategies targeting cancer neoantigens in PDAC.

Microinvasive glaucoma surgeries: critical summary of clinical trial data with and without phacoemulsification.

PURPOSE OF REVIEW: To critically summarize and examine published data from randomized controlled clinical trials (RCTs) investigating the safety and efficacy of microinvasive glaucoma surgeries (MIGS) with and without cataract surgery versus cataract surgery alone. RECENT FINDINGS: Three RCTs with standardized outcomes and rigorous methodology demonstrate superiority of the iStent (Glaukos), CyPass (Alcon), and Hydrus (Alcon) MIGS devices in combination with cataract surgery versus cataract surgery alone. The trials all involved medication washouts at baseline and also after 24 months of follow-up. In each of the trials, a greater proportion of participants randomized to the combined MIGS procedures achieved at least 20% unmedicated intraocular pressure (IOP) lowering compared with cataract surgery alone. With the exception of the CyPass device, which has been voluntarily withdrawn from the market, adverse events associated with MIGS were acceptable and consistent with routine intraocular surgeries. Follow-up studies demonstrate sustained efficacy, greater probabilities of visual field preservation, increased cost-effectiveness, and enhanced quality of life associated with MIGS procedures. SUMMARY: Data related to MIGS platforms for treatment of open-angle glaucoma with or without co-existing cataract supports their continued adoption in clinical practice. Future studies comparing various techniques and devices in a standardized fashion are needed.

Rapid Segmentation of Renal Tumours to Calculate Volume Using 3D Interpolation.

Small renal masses are commonly diagnosed with modern medical imaging. Renal tumour volume has been explored as a prognostic tool to help decide when intervention is needed and appears to provide additional prognostic information for smaller tumours compared with tumour diameter. However, the current method of calculating tumour volume in clinical practice uses the ellipsoid equation (π/6 × length × width × height) which is an oversimplified approach. Some research groups trace the contour of the tumour in every image slice which is impractical for clinical use. In this study, we demonstrate a method of using 3D segmentation software and the 3D interpolation method to rapidly calculate renal tumour volume in under a minute. Using this method in 27 patients that underwent radical or partial nephrectomy, we found a 10.07% mean absolute difference compared with the traditional ellipsoid method. Our segmentation volume was closer to the calculated histopathological tumour volume than the traditional method (p = 0.03) with higher Lin's concordance correlation coefficient (0.79 vs 0.72). 3D segmentation has many uses related to 3D printing and modelling and is becoming increasingly common. Calculation of tumour volume is one additional benefit it provides. Further studies on the association between segmented tumour volume and prognosis are needed.

Current applications of three-dimensional printing in urology.

Three-dimensional (3D) printing or additive manufacturing is a new technology that has seen rapid development in recent years with decreasing costs. 3D printing allows the creation of customised, finely detailed constructs. Technological improvements, increased printer availability, decreasing costs, improved cell culture techniques, and biomaterials have enabled complex, novel and individualised medical treatments to be developed. Although the long-term goal of printing biocompatible organs has not yet been achieved, major advances have been made utilising 3D printing in biomedical engineering. In this literature review, we discuss the role of 3D printing in relation to urological surgery. We highlight the common printing methods employed and show examples of clinical urological uses. Currently, 3D printing can be used in urology for education of trainees and patients, surgical planning, creation of urological equipment, and bioprinting. In this review, we summarise the current applications of 3D-printing technology in these areas of urology.

Solitary rib lesions showing prostate-specific membrane antigen (PSMA) uptake in pre-treatment staging 68 Ga-PSMA-11 positron emission tomography scans for men with prostate cancer: benign or malignant?

OBJECTIVES: To determine the proportion of solitary rib lesions on pre-treatment 68 Gallium-labelled prostate-specific membrane antigen (PSMA)/computed tomography (CT) scans in men with prostate cancer that are malignant and examine any predictive factors. PATIENTS AND METHODS: This retrospective single tertiary referral institution cohort study of men reviewed the results of 68 Ga-PSMA-11 positron emission tomography (PET)/CT scans performed for primary staging prior to treatment of prostate cancer from July 2014 to September 2019. Men with PSMA uptake outside the prostate in only the rib lesion were included. A solitary rib lesion was considered to be malignant if it increased in size on follow-up imaging. A lesion was considered benign if the prostate-specific antigen (PSA) level remained <0.1 µg/L following a radical prostatectomy (RP), <2 µg/L above nadir following radiotherapy (RT) as per the Phoenix criteria, histology was benign on rib biopsy, or follow-up imaging showed no growth of the rib lesion. If a lesion did not meet these criteria it was considered indeterminate. RESULTS: A total of 62 men had PSMA uptake in a solitary rib lesion; 54 went on to have RPs and eight underwent RT. In all, 61 of the men (98.4%) met the criteria for a benign rib lesion. Only one man had a false-negative malignant lesion. This man had a rib lesion with a low maximum standardised uptake value (SUVmax ) of 2.21 reported as benign, but the postoperative PSA level was 0.67 µg/L and the rib lesion progressed on follow-up imaging, with development of widespread metastases. Of the benign rib lesions, there were four false positives reported as possible metastases. Three had percutaneous rib biopsies, two of which came back with benign histology and one was indeterminate. The indeterminate biopsy patient had a RP and his postoperative PSA level was <0.1 µg/L. A total of 43 (69.4%) men with benign rib lesions had a SUVmax greater than the SUVmax of the malignant lesion. CONCLUSION: To our knowledge, this is the first cohort study of men with PSMA-avid solitary rib lesions on pre-treatment 68 Ga-PSMA PET/CT staging scans for prostate cancer. Our results indicate that the vast majority of these lesions have low-intensity uptake and are benign. Intervention to confirm this is not usually required.

Three-dimensional printing versus conventional machining in the creation of a meatal urethral dilator: development and mechanical testing.

BACKGROUND: Three-dimensional (3D) printing is a promising technology, but the limitations are often poorly understood. We compare different 3D printing methods with conventional machining techniques in manufacturing meatal urethral dilators which were recently removed from the Australian market. METHODS: A prototype dilator was 3D printed vertically orientated on a low-cost fused deposition modelling (FDM) 3D printer in polylactic acid (PLA) and acrylonitrile butadiene styrene (ABS). It was also 3D printed horizontally orientated in ABS on a high-end FDM 3D printer with soluble support material, as well as on an SLS 3D printer in medical nylon. The dilator was also machined in stainless steel using a lathe. All dilators were tested mechanically in a custom rig by hanging calibrated weights from the handle until the dilator snapped. RESULTS: The horizontally printed ABS dilator experienced failure at a greater load than the vertically printed PLA and ABS dilators, respectively (503 g vs 283 g vs 163 g, p < 0.001). The SLS nylon dilator and machined steel dilator did not fail. The steel dilator is the most expensive with a quantity of five at 98 USD each, but this decreases to 30 USD each for a quantity of 1000. In contrast, the cost for the SLS dilator is 33 USD each for five and 27 USD each for 1000. CONCLUSIONS: Low-cost FDM 3D printing is not a replacement for conventional manufacturing. 3D printing is best used for patient-specific parts, prototyping or manufacturing complex parts that have additional functionality that cannot otherwise be achieved.

Frailty, Implantable Cardioverter Defibrillators, and Mortality: a Systematic Review.

BACKGROUND: Evidence for the benefit of implantable cardioverter defibrillators (ICD) in preventing sudden cardiac death (SCD) in older adults is mixed; age alone may not predict benefit. Frailty may help identify patients in whom an ICD does not improve overall mortality risk. METHODS: Structured search of PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials on 1/31/2019, without language restriction, with terms for ICD, frailty, and mortality. Frailty was defined broadly using any validated single component (e.g., walking speed, weight loss) or multi-component tool (e.g., cumulative deficit index). Each study was assessed for quality and risk of bias. RESULTS: We identified and screened 2649 titles, reviewed 280 abstracts, and extracted 71 articles. Nine articles, including two RCTs, one prospective cohort, and six retrospective cohort studies met all criteria. The most common reason for exclusion was a lack of frailty definition. Frailty definitions were heterogeneous, including cumulative deficit models, low weight, and walking speed. Follow-up time for mortality differed: from days to > 6 years. All studies indicated that mortality was higher amongst individuals identified as frail, regardless of definition. In one RCT, slow walkers did not benefit from ICD therapy after 3 years. A cohort of 83,792 Medicare beneficiaries in an ICD registry reported higher 1-year mortality following ICD in those with frailty or dementia. Four studies reported an association between being underweight and increased mortality following ICD placement. CONCLUSION: Existing literature suggests that individuals with frailty may not benefit from ICD placement for primary prevention of SCD.

Hospice utilization in advanced cervical malignancies: An analysis of the National Inpatient Sample.

OBJECTIVE: Hospice services improve quality of life and outcomes for patients and caretakers, compared to inpatient mortality. This study identifies factors that exert the strongest influence on end-of-life care modalities in patients with cervical cancer. METHODS: Admissions with a diagnosis of cervical cancer that were discharged to hospice or died in-hospital were identified in the National Inpatient Sample years 2007-2011, excluding admissions coded for hysterectomy. Logistic regression models were used to examine differences in age, race, length of stay, primary payer, hospital region, admission type, hospital bedsize, hospital teaching status, income quartile, and Elixhauser comorbidity index score between the groups. RESULTS: 2073 admissions with a diagnosis of cervical cancer resulting in hospice discharge (n = 1290) or inpatient death (n = 783) were identified. Age (P = 0.01), hospital region (P = 0.01), length of hospitalization (P < 0.01), Elixhauser comorbidity index score (P = 0.03), and urban vs. rural location (P = 0.01) had a significant impact on disposition in univariate analysis. Admissions of patients categorized as Asian/Pacific Islander (OR = 2.24, 95% CI 1.11-4.49), hospitalizations lasting 0-3 days (OR = 1.57, 95% CI 1.21-2.03), and admissions in rural areas (OR = 1.62, 95% CI 1.12-2.36) had higher rates of in-hospital death compared to the reference groups. Patients aged 18-45 years (OR = 0.69, 95% CI 0.52-0.90) and those treated in the South (OR 0.59, 95% CI 0.45-0.77) and West (OR = 0.50, 95% CI 0.30-0.81) had lower odds ratios of inpatient mortality. CONCLUSION: Modalities of care in terminal cervical cancer vary among sociodemographic and clinical factors. This data underscores the continued push for improved end-of-life care among cervical cancer patients and can guide clinicians in appropriate targeted counseling to increase utilization of hospice resources.

New quantitative classification of the anatomical relationship between impacted third molars and the inferior alveolar nerve.

BACKGROUND: Before extracting impacted lower third molars, dentists must first identify the spatial relationship between the inferior alveolar nerve (IAN) and an impacted lower third molar to prevent nerve injury from the extraction. Nevertheless, the current method for describing the spatial relationship between the IAN and an impacted lower third molar is deficient. Therefore, the objectives of this study were to: (1) evaluate the relative position between impacted lower third molars and the IAN; and (2) investigate the relative position between impacted lower third molars and the IAN by using a cylindrical coordinate system. METHODS: From the radiology department's database, we selected computed tomography images of 137 lower third molars (from 75 patients) requiring removal and applied a Cartesian coordinate system by using Mimics, a medical imaging software application, to measure the distribution between impacted mandibular third molars and the IAN. In addition, the orientation of the lower third molar to the IAN was also measured, but by using a cylindrical coordinate system with the IAN as the origin. RESULTS: According to the Cartesian coordinate system, most of the IAN runs through the inferior side of the third molar (78.6 %), followed by the lingual side (11.8 %), and the buccal side (8.9 %); only 0.7 % is positioned between the roots. Unlike the Cartesian coordinate system, the cylindrical coordinate system clearly identified the relative position, r and θ, between the IAN and lower third molar. CONCLUSIONS: Using the cylindrical coordinate system to present the relationship between the IAN and lower third molar as (r, θ) might provide clinical practitioners with a more explicit and objective description of the relative position of both sites. However, comprehensive research and cautious application of this system remain necessary.

[Not Available].

UNLABELLED: Saphenous vein graft (SVG) failure secondary to degeneration can cause significant problems after coronary artery bypass surgery (CABG). Repeat revascularization by percutaneous coronary intervention can be performed after SVG failure but is often associated with less favourable clinical outcome. Treatment for chronic total occlusion (CTO) of native vessels after SVG failure among patients with prior CABG is frequently performed. However, revascularization of CTO vessels in patients with prior CABG may be more complex and require more frequent use of the retrograde approach. Good septal or epicardial collateral channels are usually needed for the retrograde CTO approach. However, suitable native collateral channels may be absent and alternative retrograde routes should be considered. In this case report, we described a patient who had prior CABG and developed recurrent angina after SVG failure. His native CTO lesion was successfully revascularized by using a totally occluded vein graft as a retrograde conduit. KEY WORDS: Chronic total occlusions; Coronary artery bypass grafts; Percutaneous coronary intervention; Saphenous vein graft.

Delayed Infective Endocarditis with Mycotic Aneurysm Rupture below the Mechanical Valved Conduit after the Bentall Procedure.

UNLABELLED: The Bentall procedure is the gold standard for treating aortic dissection complicated with valvular and ascending aorta disease. Recent results for this procedure have been excellent; nearly 100% of patients remain free of infective endocarditis in long-term follow-up. We report a case of delayed Streptococcus agalactiae infective endocarditis complicated by mycotic aneurysm in a man who had undergone the Bentall procedure with a mechanical valve conduit 15 years previously. The mycotic aneurysm was located in the remnant aortic root, below the mechanical valve conduit, and later ruptured into the right atrium. The patient was treated conservatively and survived the acute period. Later, the aortic root defect was repaired successfully by means of a hybrid technique using a Amplatzer duct occluder. KEY WORDS: Amplatzer duct occluder; Aortic dissection; Bentall technique; Infective endocarditis; Mycotic aneurysm.

Chronic high-dose testosterone impairs economic decision making, but has no effect on memory in male rats.

The goal is to understand consequences of anabolic-androgenic steroid (AAS) abuse on cognitive function, using rats as a model. Economic decision making was evaluated in an operant test of effort value discounting, where subjects choose between 2 levers that deliver large and small rewards differing in maximum value and reward contrast. The hypothesis is that chronic high-dose testosterone increases preference for large rewards. Male rats were treated chronically with testosterone (7.5 mg/kg) or vehicle. Initially, all rats preferred the large reward lever when large and small rewards remained fixed at 3 and 1 sugar pellets, respectively. When different reward values were introduced, and with increasing response requirements, testosterone-treated rats made fewer responses for the large reward, and increased omissions. They earned fewer rewards overall. To determine if testosterone impairs memory, rats were tested for recognition memory with the novel object recognition and social transmission of food preference tasks, and for spatial memory with the radial arm maze and Morris water maze. There was not effect of chronic high-dose testosterone on any memory task. These results suggest that testosterone shifts economic decision making towards larger rewards even when they are disadvantageous, but does not alter memory in rats.

Dendritic cell subsets and implications for cancer immunotherapy.

Dendritic cells (DCs) play a central role in the orchestration of effective T cell responses against tumors. However, their functional behavior is context-dependent. DC type, transcriptional program, location, intratumoral factors, and inflammatory milieu all impact DCs with regard to promoting or inhibiting tumor immunity. The following review introduces important facets of DC function, and how subset and phenotype can affect the interplay of DCs with other factors in the tumor microenvironment. It will also discuss how current cancer treatment relies on DC function, and survey the myriad ways with which immune therapy can more directly harness DCs to enact antitumor cytotoxicity.

Preoperative assessment of bone density for dental implantation: a comparative study of three different ROI methods.

BACKGROUND: Dental cone beam computed tomography (CBCT) is commonly used to evaluate cancellous bone density before dental implant surgery. However, to our knowledge, no measurement approach has been standardized yet. This study aimed to evaluate the relationship between three different regions of interest (ROI) methods on cancellous bone density at the dental implant site using dental CBCT images. METHODS: Patients' dental CBCT images (n = 300) obtained before dental implant surgery were processed using Mimics (Materialise, Leuven, Belgium). At the potential implant sites, the rectangle, cylinder, and surrounding cylinder ROI methods were used to measure bone density. Repeated measures one-way analysis of variance was performed to compare the three ROI methods in terms of measurement results. Pearson correlation analysis was performed to identify the likely pair-wise correlations between the three ROI methods. RESULTS: The density value obtained using the surrounding cylinder approach (grayscale value [GV],523.56 ± 228.03) was significantly higher than the values obtained using the rectangle (GV, 497.04 ± 236.69) and cylinder (GV,493 ± 231.19) ROI methods in terms of results. Furthermore, significant correlations were noted between the ROI methods (r > 0.965; p < 0.001). CONCLUSIONS: The density measured using the surrounding cylinder method was the highest. The choice of method may not influence the trends of measurement results. TRIAL REGISTRATION: This study was approved by the Institutional Review Board of China Medical University Hospital, No. CMUH111-REC3-205. Informed consent was waived by the Institutional Review Board of China Medical University Hospital, CMUH111-REC3-205, owing to the retrospective nature of the study.

Imaging-guided radiofrequency ablation of cystic renal neoplasms.

OBJECTIVE: The purpose of this article is to determine whether percutaneous radiofrequency ablation (RFA) is effective and safe for the treatment of cystic renal neoplasms. MATERIALS AND METHODS: This is a retrospective review of imaging-guided RFA of Bosniak III and IV cysts from one institution. Thirty-eight subjects (19 men and 19 women; mean age, 71 years; age range, 46-95 years) underwent RFA of 40 cystic neoplasms (Bosniak III, n = 25; Bosniak IV, n = 15). Percutaneous biopsy was performed in 90% (36/40) of lesions. For patients with imaging follow-up of at least 1 year (n = 21), the mean duration of surveillance was 2.8 years (range, 1-6.5 years). The electronic medical record was reviewed for complications related to the procedure. Estimated glomerular filtration rate (GFR) was measured before RFA and at the last follow-up visit more than 6 months after the RFA session. RESULTS: According to percutaneous biopsy, 61.1% (22/36) of lesions were malignant, and 38.9% (14/36) of biopsies were inconclusive. There was no local tumor progression, and no subjects developed metastatic disease. One subject developed a new solid renal mass during the course of follow-up. Minor complications occurred in 5.3% (2/38) of ablations and included dysuria and mild hydronephrosis related to a blood clot in the ureter. There was one major complication (2.6%), a case of flash pulmonary edema. On average, estimated GFR decreased by 2.5 mL/min/1.73 m(2). CONCLUSION: Imaging-guided RFA is an effective and safe treatment of Bosniak III and IV cystic renal neoplasms with outcomes comparable to those of surgical therapies.

Trabecular bone structural parameters evaluated using dental cone-beam computed tomography: cellular synthetic bones.

OBJECTIVE: This study compared the adequacy of dental cone beam computed tomography (CBCT) and micro computed tomography (micro-CT) in evaluating the structural parameters of trabecular bones. METHODS: The cellular synthetic bones in 4 density groups (Groups 1-4: 0.12, 0.16, 0.20, and 0.32 g/cm3) were used in this study. Each group comprised 8 experimental specimens that were approximately 1 cm3. Dental CBCT and micro-CT scans were conducted on each specimen to obtain independent measurements of the following 4 trabecular bone structural parameters: bone volume fraction (BV/TV), specific bone surface (BS/BV), trabecular thickness (Tb.Th.), and trabecular separation (Tb.Sp.). Wilcoxon signed ranks tests were used to compare the measurement variations between the dental CBCT and micro-CT scans. A Spearman analysis was conducted to calculate the correlation coefficients (r) of the dental CBCT and micro-CT measurements. RESULTS AND CONCLUSION: Of the 4 groups, the BV/TV and Tb.Th. measured using dental CBCT were larger compared with those measured using micro-CT. By contrast, the BS/BV measured using dental CBCT was significantly less compared with those measured using micro-CT. Furthermore, in the low-density groups (Groups 1 and 2), the Tb.Sp. measured using dental CBCT was smaller compared with those measured using micro-CT. However, the Tb.Sp. measured using dental CBCT was slightly larger in the high-density groups (Groups 3 and 4) than it was in the low density groups. The correlation coefficients between the BV/TV, BS/BV, Tb.Th., and Tb.Sp. values measured using dental CBCT and micro-CT were 0.9296 (p < .001), 0.8061 (p < .001), 0.9390 (p < .001), and 0.9583 (p < .001), respectively. Although the dental CBCT and micro-CT approaches exhibited high correlations, the absolute values of BV/TV, BS/BV, Tb.Th., Tb.Sp. differed significantly between these measurements. Additional studies must be conducted to evaluate using dental CBCT in clinical practice.

Microcomputed tomography analysis of particular autogenous bone graft in sinus augmentation at 5 months: differences on bone mineral density and 3D trabecular structure.

OBJECTIVES: This study investigated the effects of gender on the three-dimensional (3D) bone mineral density (BMD) and micromorphology of the trabeculae of matured autogenous bone grafts after sinus floor augmentation, and compared them to those of adjacent native bone. MATERIALS AND METHODS: Ten bone biopsy samples were removed from the implant placement areas of patients who had received second-stage sinus floor augmentation, and analyzed by microcomputed tomography. BMD phantoms with two calcium hydroxyapatite densities (0.25 and 0.75 g/cm(3)) were used to determine the BMD of the grafted and native bone samples. The 3D structural parameters of the trabeculae, including percentage of bone volume (bone volume/tissue volume, BV/TV), trabecular thickness (Tb.Th), trabecular number, trabecular separation, trabecular pattern factor (Tb.Pf), and structure model index, were analyzed between males and females and between grafted bone and native bone. RESULTS: No significant gender-specific differences in BMD and 3D trabecular structure of either native or grafted bone were found (P > 0.05). Compared to the adjacent native bone, the autogenous grafted bone exhibited lower BV/TV and Tb.Th as well as a higher Tb.Pf (P < 0.05). Additionally, there was a weak positive correlation between the Tb.Th values of grafted and native bone (R (2) = 0.58). CONCLUSIONS: In the maxillary sinus, autogenous grafted bone exhibited lower BV/TV, Tb.Th, and trabecular connectivity than the adjacent native bone. No significant gender-specific differences were found for either the BMD or 3D trabecular structure of grafted bone. CLINICAL RELEVANCE: After bone remodeling, autogenous grafted bone revealed different 3D trabecular structure as compared to native bone.

IL-6 selectively suppresses cDC1 specification via C/EBPß.

Cytokines produced in association with tumors can impair antitumor immune responses by reducing the abundance of type 1 conventional dendritic cells (cDC1), but the mechanism remains unclear. Here, we show that tumor-derived IL-6 generally reduces cDC development but selectively impairs cDC1 development in both murine and human systems through the induction of C/EBPß in the common dendritic cell progenitor (CDP). C/EBPß and NFIL3 compete for binding to sites in the Zeb2 -165 kb enhancer and support or repress Zeb2 expression, respectively. At homeostasis, pre-cDC1 specification occurs upon Nfil3 induction and consequent Zeb2 suppression. However, IL-6 strongly induces C/EBPß expression in CDPs. Importantly, the ability of IL-6 to impair cDC development is dependent on the presence of C/EBPß binding sites in the Zeb2 -165 kb enhancer, as this effect is lost in Δ1+2+3 mutant mice in which these binding sites are mutated. These results explain how tumor-associated IL-6 suppresses cDC1 development and suggest therapeutic approaches preventing abnormal C/EBPß induction in CDPs may help reestablish cDC1 development to enhance antitumor immunity.