Occupational noise-induced hearing loss among dental personnel: a scoping review.

Introduction Dental personnel are being exposed to noisy equipment on a daily basis and there are indications that dental professionals are at a higher risk of developing occupational noise-induced hearing loss (NIHL). Therefore, this study aims to assess the available research on NIHL among dental professionals.Methods A total of 452 publications were identified through searches on PubMed and Web of Science. These studies were screened on title and abstract for studies that investigated NIHL among dental professionals using objective or subjective parameters for hearing loss. The remaining publications were then searched for relevant data, such as research type, parameters used for measuring hearing loss and authors' conclusions.Results In total, 28 publications were finally included in the selection. Of this selection, 23 used objective criteria for NIHL, three used subjective criteria and two used both. From the 12 studies with objective measurements that also included a control group in their studies, eight reported a significant higher hearing loss among dental personnel than in the control groups. From the 13 studies with objective measurement without a control group, seven reported significant hearing loss among dental personnel. All five studies with subjective measurements reported significant hearing loss in dental personnel.Conclusions Hearing loss seems to be more prevalent among dental personnel than in most control groups.

Fecal proteolytic profiling of pediatric inflammatory bowel disease: A pilot study.

Colonoscopy is the gold standard for diagnosing inflammatory bowel disease (IBD). However, this invasive procedure has a high burden for pediatric patients. Previous research has shown elevated fecal amino acid concentrations in children with IBD versus controls. We hypothesized that this finding could result from increased proteolytic activity. Therefore, the aim of this study was to investigate whether fecal protease-based profiling was able to discriminate between IBD and controls. Protease activity was measured in fecal samples from patients with IBD (Crohn's disease (CD) n = 19; ulcerative colitis (UC) n = 19) and non-IBD controls (n = 19) using a fluorescence resonance energy transfer (FRET)-peptide library. Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic value of each FRET-peptide substrate. Screening the FRET-peptide library revealed an increased total proteolytic activity (TPA), as well as degradation of specific FRET-peptides specifically in fecal samples from IBD patients. Based on level of significance (p < .001) and ROC curve analysis (AUC > 0.85), the fluorogenic substrates W-W, A-A, a-a, F-h, and H-y showed diagnostic potential for CD. The substrates W-W, a-a, T-t, G-v, and H-y showed diagnostic potential for UC based on significance (p < .001) and ROC analysis (AUC > 0.90). None of the FRET-peptide substrates used was able to differentiate between protease activity in fecal samples from CD versus UC. This study showed an increased fecal proteolytic activity in children with newly diagnosed, treatment-naïve, IBD. This could lead to the development of novel, noninvasive biomarkers for screening and diagnostic purposes.

Enhanced aortic stiffness in adolescents with chronic disease is associated with decreased left ventricular global longitudinal strain.

Background: The recent Cardiovascular Disease in Adolescents with Chronic Disease (CDACD) study showed enhanced aortic stiffness and wall thickness in adolescents with various chronic disorders. Enhanced aortic stiffness can increase left ventricular (LV) afterload and trigger a cascade of adverse arterioventricular interaction. Here, we investigate the relation between aortic changes and LV function in the CDACD study participants. Methods: This cross-sectional study included 114 adolescents 12-18 years old with cystic fibrosis (CF, n = 24), corrected coarctation of the aorta (CoA, n = 25), juvenile idiopathic arthritis (JIA, n = 20), obesity (n = 20), and healthy controls (n = 25). Aortic pulse wave velocity (PWV), which reflects aortic stiffness, and aortic wall thickness (AWT) were assessed with cardiovascular magnetic resonance imaging (CMR). Echocardiography was employed to study conventional markers of LV function, as well as LV global longitudinal strain (LVGLS), which is an established (pre)clinical marker of LV dysfunction. Results: First, aortic PWV and AWT were increased in all chronic disease groups, compared to controls. Second, in adolescents with CoA, JIA, and obesity, echocardiography showed a decreased LVGLS, while LV dimensions and conventional LV function markers were similar to controls. Third, multivariable linear regression identified aortic PWV as the most important determinant of their decreased LVGLS (standardized ß -0.522, p < 0.001). Conclusions: The decreased LVGLS in several adolescent chronic disease groups was associated with enhanced aortic PWV, which might reflect adverse arterioventricular interaction. Whether the decreased LVGLS in the chronic disease groups could negatively impact their long-term cardiovascular outcomes requires further study.

Understanding changes in echocardiographic parameters at different ages following fetal growth restriction: a systematic review and meta-analysis.

Fetal growth restriction (FGR) increases cardiovascular risk by cardiac remodeling and programming. This systematic review and meta-analysis across species examines the use of echocardiography in FGR offspring at different ages. PubMed and Embase.com were searched for animal and human studies reporting on echocardiographic parameters in placental insufficiency-induced FGR offspring. We included six animal and 49 human studies. Although unable to perform a meta-analysis of animal studies because of insufficient number of studies per individual outcome, all studies showed left ventricular dysfunction. Our meta-analyses of human studies revealed a reduced left ventricular mass, interventricular septum thickness, mitral annular peak velocity, and mitral lateral early diastolic velocity at neonatal age. No echocardiographic differences during childhood were observed, although the small age range and number of studies limited these analyses. Only two studies at adult age were performed. Meta-regression on other influential factors was not possible due to underreporting. The few studies on myocardial strain analysis showed small changes in global longitudinal strain in FGR offspring. The quality of the human studies was considered low and the risk of bias in animal studies was mostly unclear. Echocardiography may offer a noninvasive tool to detect early signs of cardiovascular predisposition following FGR. Clinical implementation yet faces multiple challenges including identification of the most optimal timing and the exact relation to long-term cardiovascular function in which echocardiography alone might be limited to reflect a child's vascular status. Future research should focus on myocardial strain analysis and the combination of other (non)imaging techniques for an improved risk estimation.NEW & NOTEWORTHY Our meta-analysis revealed echocardiographic differences between fetal growth-restricted and control offspring in humans during the neonatal period: a reduced left ventricular mass and interventricular septum thickness, reduced mitral annular peak velocity, and mitral lateral early diastolic velocity. We were unable to pool echocardiographic parameters in animal studies and human adults because of an insufficient number of studies per individual outcome. The few studies on myocardial strain analysis showed small preclinical changes in FGR offspring.

Radiographic Detection Rate of Distal Surface Caries in the Mandibular Second Molar in Populations with Different Third Molar Management Strategies: A Multicenter Study.

Background: Distal surface caries (DSC) has been associated with partially erupted impacted third molars. The purpose of this study was to compare the rates of DSC between populations that had undergone different third molar management strategies. Methods: Radiographs that had been taken during routine examinations of 1012, 251 and 250 patients in Manchester, Bucharest and Amsterdam, respectively, were evaluated. The following parameters were assessed: the state of the distal surface in the second mandibular molar, loss of periodontal support, impaction type of the third molar, contact point localization, and patients' genders, ages and their cumulative history of dental health. Results: The rate of DSC in the second mandibular molar was 63.9%, 19.9% and 26.0% in the Manchester, Bucharest and Amsterdam populations, respectively. A loss of lamina dura of ≥2 mm, increased percentages of decayed, missing or filled teeth and male gender were risk factors in all three populations. All assessed parameters apart from the site of the mandible reached statistical significance in the Manchester sample (p < 0.001). The DSC rate was cumulative with increasing age in the Manchester population, in which third molars were strategically retained. Conclusions: The UK population, treated according to strict guidelines that limit the removal of third molars, had a statistically significant higher DSC prevalence rate (p < 0.001) than the Romanian or Dutch populations. The active surgical management of mandibular third molars seems to have the potential to reduce the DSC rate in the adjacent second molar.

Orodental injury and mouthguard usage in Dutch and international field hockey.

Background: Mouthguards are used to prevent players from orodental injuries in field hockey. However, such injuries are still a common problem. This study describes the prevalence of orodental injury and the related mouthguard usage in field hockey. Material and Methods: A 19-item questionnaire was distributed in the Dutch field hockey competition and at the international Master World Cup. In total, 1213 questionnaires were collected. Standard descriptive statistics were used to describe the samples. Associations between data were determined using the Pearson Chi-Square test. Results: The prevalence of orodental injuries during the career of hockey players was 20% in Dutch players, and 29% in international players. Mouthguard usage among Dutch players was 95%, and among international players 88%. There was no significant association between wearing a mouthguard or not with respect to whether or not treatment was requested as a result of an orodental injury (Dutch p=0.43; international p=0.22). Conclusions: This study showed that the prevalence of orodental injuries in field hockey are high, while the majority of the players use a 'protective' mouthguard. These results imply that the current mouthguards may not provide enough protection against the forces used in field hockey. Key words:Mouthguard, prevention, sports, dental injury.

Carbon dots combined with phytosphingosine inhibit acid-induced demineralization of hydroxyapatite in vitro.

OBJECTIVES: To study the effects of carbon dots (CDs), in combination with phytosphingosine (PHS), against acid-induced demineralization of hydroxyapatite in vitro. METHODS: CDs were generated from citric acid and urea by microwave heating. Transmission electron microscope (TEM), FT-IR, and fluorescence intensity were used to characterize the CDs. A hydroxyapatite (HAp) model was used to investigate the protective effects of CDs, PHS, and their combinations with and without a salivary pellicle against acid-induced demineralization in vitro. Ca2+ release as a parameter to evaluate the inhibition of demineralization was measured by capillary electrophoresis. The interactions between CDs, PHS, and HAp discs were investigated using a fluorescence detector. RESULTS: Uniform-sized CDs were synthesized, showing typical optical characteristics. CDs exhibited no inhibition of acid-induced demineralization in vitro, in contrast to PHS. Notably, a pre-coating of CDs increased the protective effects of PHS against acid-induced demineralization, which was not disturbed by the presence of a salivary pellicle and Tween 20. Scanning electron microscope (SEM) confirmed the binding and layers formed of both CDs and PHS to the HAp surfaces. Based on fluorescence spectra CDs binding to HAp seemed to be dependent on Ca2+ and PO43- interactions. CONCLUSIONS: CDs combined with PHS showed protective effects against acid-induced demineralization of HAp discs in vitro.

Late Complications in Long-Term Childhood Cancer Survivors: What the Oral Health Professional Needs to Know.

With diagnostic and therapeutic advances, over 80% of children diagnosed with cancer become long-term survivors. As the number of childhood cancer survivors (CCS) continues to increase, dental practitioners become more likely to have CCS among their patients. CCS may develop late complications from damage caused by their cancer treatment to endocrine, cardiovascular, musculoskeletal, and other organ systems. These complications may surface decades after the completion of treatment. Adverse outcomes of childhood cancer treatment frequently involve oral and craniofacial structures including the dentition. Tooth development, salivary gland function, craniofacial growth, and temporomandibular joint function may be disturbed, increasing oral health risks in these individuals. Moreover, CCS are at risk of developing subsequent malignancies, which may manifest in or near the oral cavity. It is important that dental practitioners are aware of the childhood cancer history of their patients and have knowledge of potential late complications. Therefore, this narrative review aims to inform dental practitioners of late oral complications of cancer treatment modalities commonly used in pediatric oncology. Furthermore, selected common non-oral late sequelae of cancer therapy that could have an impact on oral health and on delivering dental care will be discussed.

Dutch dental hygiene students' knowledge of HPV-related oropharyngeal squamous cell carcinoma and HPV vaccination.

INTRODUCTION: The incidence of human papillomavirus (HPV)-related oropharyngeal cancer is rising, thus the understanding of HPV infection and vaccination among oral healthcare professionals is becoming increasingly important. This study aimed to investigate the knowledge of Dutch dental hygiene students on HPV infection and vaccination and assessed various aspects of HPV-related oropharyngeal cancer. METHODS: This descriptive cross-sectional study invited the entire Dutch dental hygiene student population registered in September 2016 to complete an online questionnaire concerning the knowledge of HPV infection and vaccination, including the aspects of HPV-related Oro-Pharyngeal Squamous Cell Carcinoma (OPSCC). Data were analysed using t-tests, Mann-Whitney U tests and Chi-square tests. RESULTS: Invited were all 1248 Dutch dental hygiene students and 232 (18.6%) students completed the questionnaire. More than 95% of the students indicated HPV infection as a risk factor for OPSCC and 48.7% was aware of the availability of HPV vaccination. Additionally, students considered it important to discuss HPV as a risk factor for oropharyngeal cancer with their patients. In general, the students scored highest on the questions about risk factors for OPSCC and poorest on the questions about general HPV knowledge and HPV vaccination. Although the mean overall knowledge score was significantly higher in senior compared with junior students, knowledge scores of senior students remained insufficient. CONCLUSION: This study identified deficits in knowledge of HPV and HPV vaccination among Dutch dental hygiene students. Future research should focus on improving the content of dental hygiene curricula and development of ongoing educational tools for dental hygienists.

Dyslipidaemia as a target for atherosclerotic cardiovascular disease prevention in children with type 1 diabetes: lessons learned from familial hypercholesterolaemia.

In the last few decades, atherosclerotic cardiovascular disease (ASCVD) risk has decreased dramatically among individuals affected by familial hypercholesterolaemia (FH) as a result of the early initiation of statin treatment in childhood. Contemporaneously important improvements in care for people with diabetes have also been made, such as the prevention of mortality from acute diabetic complications. However, individuals with type 1 diabetes still have a two to eight times higher risk of death than the general population. In the last 20 years, a few landmark studies on excess mortality in people with type 1 diabetes, in particular young adults, have been published. Although these studies were carried out in different populations, all reached the same conclusion: individuals with type 1 diabetes have a pronounced increased risk of ASCVD. In this review, we address the role of lipid abnormalities in the development of ASCVD in type 1 diabetes and FH. Although type 1 diabetes and FH are different diseases, lessons could be learned from the early initiation of statins in children with FH, which may provide a rationale for more stringent control of dyslipidaemia in children with type 1 diabetes.

The minimally important difference for the Xerostomia Inventory among Sjögren's disease patients.

OBJECTIVE: Until now, the clinically relevant improvement for the Xerostomia Inventory (XI) has not been defined. Therefore, our aim was to determine the Minimally Important Difference (MID) of the XI for improvement in dry-mouth symptoms in SjD patients. METHOD: The study recruited 34 SjD patients who underwent sialendoscopy of major salivary glands and 15 SjD patients in a nonintervention control group. XI scores were assessed at several time points. The MID was determined from the mean difference in XI scores between the groups with and without improvement. RESULTS: In the control group, no significant XI score changes were seen. In the sialendoscopy group, a clinically relevant XI score change of four scale points was identified after 1 week. For a prolonged duration (≥16 weeks), a minimum reduction of seven scale points in the XI score was required to indicate clinically relevant improvement. CONCLUSION: In SjD patients, a minimum change of four points in the XI score indicates a clinically relevant improvement for evaluating short-term effects. For prolonged effects, a clinically relevant improvement requires a MID of seven points. The determination of the MID in XI could assist in future studies that evaluate changes in xerostomia.

Implant supported overdentures in Sjögren's disease patients: a multicentre prospective cohort study.

OBJECTIVES: To prospectively investigate patient-reported outcomes and clinical performance of implant supported overdentures in edentulous Sjögren's disease (SjD) patients compared to subjects without SjD. METHODS: 51 implants were placed in 12 patients with SjD and 50 implants in 12 non-SjD patients to support overdentures. Clinical performance, marginal bone-level changes, patient satisfaction and oral health related quality of life (OHRQoL) were assessed at 1 (T1), 6 (T6), 12 (T12) and 18 (T18) months after placement of the overdenture. Patient satisfaction, ability to chew and OHRQoL were assessed with validated questionnaires. Marginal bone-level changes were measured on standardised dental radiographs. Clinical parameters included implant and overdenture survival, plaque, bleeding and gingival indices, and probing depth. RESULTS: OHRQoL in patients with SjD improved significantly after placement of implant supported overdentures at all measuring moments compared to baseline (p<0.05). Nevertheless, ability to chew tough and hard food was significantly better for non-SjD patients at all timepoints after placement of an implant supported overdenture (p<0.05). Implant survival at T18 was 100% in the patients with SjD and 98% in the non-SS group. Mean marginal bone loss at T18 did not differ between patients with SjD and non-SS patients, 1.12±0.74 mm and 1.43±1.66 mm, respectively (p=0.58). Clinical performance was good with no differences between the groups for all outcome measures (p>0.05). CONCLUSIONS: Implant-supported overdentures have a positive effect on OHRQoL and dental implants can be successfully applied in edentulous patients with SjD with nearly similar outcomes as in non-SjD subjects.

Hypercoordination by Multiple Dangling Benzylmethoxy Ligands in Highly Crowded Triaryltin Bromide [(2-MeOCH2 C6 H4 )]3 SnBr and Diaryltin Mixed Halides [(2-MeOCH2 C6 H4 )]2 SnBrCl, and a related Distannane and Distannoxane.

The reaction between the Grignard reagent formed from Mg and 2-bromobenzylmethyl ether and SnCl4 produced four products: [2-(MeOCH2 )C6 H4 ]3 SnBr (1), [2-(MeOCH2 )C6 H4 ]2 SnX2 (2, X2 =Br2 (a) and BrCl (b)), [{2-(MeOCH2 )C6 H4 }3 Sn]2 (3), and [{2-(MeOCH2 )C6 H4 }2 SnBr]2 O (4). In the case of 1, two of the three dangling arm O atoms coordinate to the central tin atom with O-Sn internuclear distances of 2.53 (O1) and 2.91 (O2) Å, the shorter interaction being trans to the Br atom, the other trans to a phenyl carbon atom. In the case of 2a the resulting hexacoordinate structure exhibits two very short O-Sn interactions of 2.42 and 2.50 Å, well below the sum of the VdW radii of O and Sn, 3.69 Å. The sterically crowded ditin compound 3 was obtained in trace amounts and the structure demonstrates no dangling O-Sn interactions. General changes in structure compared to other distannane systems are reflective of the great steric crowding. Distannoxane 4, has a Sn-O-Sn bond angle of 148.1(2)° which is larger compared to other distannoxane structures. The intermolecular interactions between Sn-O 2.470(3) and 2.521(3)Å and 2.665(3) and 2.629(3)Å for Sn1 and Sn2 respectively are responsible for a distorted octahedral geometry around the two tin atoms. The various 119 Sn, 13 C and 1 H NMR spectra are in accord with their structural analysis for 1 and 2, and in the solid state 13 C NMR spectrum of 1 the dangling methylene group is observable whereas is solution there is a rapid dynamic equilibrium resulting in a single resonance for all methylene groups.

The applications of carbon dots in oral health: A scoping review.

OBJECTIVES: This scoping review aims to provide an overview of the research and potential applications of carbon dots (CDs) for oral health purposes. DESIGN: Systematic literature searches were performed on PubMed and Web of Science databases (up to February 2023). Two co-authors selected the published works independently and extracted the data in accordance with the PRISMA statement. Studies with the application of CDs for oral health purposes were included. RESULTS: Among 152 articles, 19 articles were finally selected. Eight studies investigated the anti-microbial effects of CDs against, for example, oral pathogens, eight studies explored the applicability of CDs in relation to oral cancer, and three studies investigated CDs in relation to cell differentiation and tissue regeneration in oral health. The studies showed the promising potential of CDs in oral health, particularly for inducing bacterial killing by increasing reactive oxygen species, killing oral cancer cells via photodynamic therapeutic effects, and inducing dental pulp and periodontal bone regeneration. CONCLUSION: The findings show that CDs have the potential to be utilized in the future for various oral health purposes. Besides, these results underline the broad-spectrum applicability of CDs, crossing the borders of oral health.

Cortical morphology in patients with the deficit and non-deficit syndrome of schizophrenia: a worldwide meta- and mega-analyses.

Converging evidence suggests that schizophrenia (SZ) with primary, enduring negative symptoms (i.e., Deficit SZ (DSZ)) represents a distinct entity within the SZ spectrum while the neurobiological underpinnings remain undetermined. In the largest dataset of DSZ and Non-Deficit (NDSZ), we conducted a meta-analysis of data from 1560 individuals (168 DSZ, 373 NDSZ, 1019 Healthy Controls (HC)) and a mega-analysis of a subsampled data from 944 individuals (115 DSZ, 254 NDSZ, 575 HC) collected across 9 worldwide research centers of the ENIGMA SZ Working Group (8 in the mega-analysis), to clarify whether they differ in terms of cortical morphology. In the meta-analysis, sites computed effect sizes for differences in cortical thickness and surface area between SZ and control groups using a harmonized pipeline. In the mega-analysis, cortical values of individuals with schizophrenia and control participants were analyzed across sites using mixed-model ANCOVAs. The meta-analysis of cortical thickness showed a converging pattern of widespread thinner cortex in fronto-parietal regions of the left hemisphere in both DSZ and NDSZ, when compared to HC. However, DSZ have more pronounced thickness abnormalities than NDSZ, mostly involving the right fronto-parietal cortices. As for surface area, NDSZ showed differences in fronto-parietal-temporo-occipital cortices as compared to HC, and in temporo-occipital cortices as compared to DSZ. Although DSZ and NDSZ show widespread overlapping regions of thinner cortex as compared to HC, cortical thinning seems to better typify DSZ, being more extensive and bilateral, while surface area alterations are more evident in NDSZ. Our findings demonstrate for the first time that DSZ and NDSZ are characterized by different neuroimaging phenotypes, supporting a nosological distinction between DSZ and NDSZ and point toward the separate disease hypothesis.

Intraoperative Visualization and Treatment of Salivary Gland Dysfunction in Sjögren's Syndrome Patients Using Contrast-Enhanced Ultrasound Sialendoscopy (CEUSS).

In sialendoscopy, ducts are dilated and the salivary glands are irrigated with saline. Contrast-enhanced ultrasound sialendoscopy (CEUSS), using microbubbles, may facilitate the monitoring of irrigation solution penetration in the ductal system and parenchyma. It is imperative to test CEUSS for its safety and feasibility in Sjögren's syndrome (SS) patients. CEUSS was performed on 10 SS patients. The primary outcomes were safety, determined by the occurrence of (serious) adverse events ((S)AEs), and feasibility. The secondary outcomes were unstimulated and stimulated whole saliva (UWS and SWS) flow rates, xerostomia inventory (XI), clinical oral dryness score, pain, EULAR Sjögren's syndrome patient reported index (ESSPRI), and gland topographical alterations. CEUSS was technically feasible in all patients. Neither SAEs nor systemic reactions related to the procedure were observed. The main AEs were postoperative pain (two patients) and swelling (two patients). Eight weeks after CEUSS, the median UWS and SWS flow had increased significantly from 0.10 to 0.22 mL/min (p = 0.028) and 0.41 to 0.61 mL/min (p = 0.047), respectively. Sixteen weeks after CEUSS, the mean XI was reduced from 45.2 to 34.2 (p = 0.02). We conclude that CEUSS is a safe and feasible treatment for SS patients. It has the potential to increase salivary secretion and reduce xerostomia, but this needs further investigation.

Self-reported outcomes on oral health and oral health-related quality of life in long-term childhood cancer survivors-A DCCSS-LATER 2 Study.

PURPOSE: The present study aimed to determine the prevalence of self-reported oral problems and the oral health-related quality of life (OHRQoL) in childhood cancer survivors (CCS). METHODS: Patient and treatment characteristics of CCS have been collected in a cross-sectional study, part of the multidisciplinary DCCSS-LATER 2 Study. To assess self-reported oral health problems and dental problems, CCS filled out the 'Toegepast-Natuurwetenschappelijk Onderzoek' (TNO) oral health questionnaire. OHRQoL was assessed by the Dutch version of the Oral Health Impact Profile-14 (OHIP-14). Prevalences were compared with two comparison groups from the literature. Univariable and multivariable analyses were performed. RESULTS: A total of 249 CCS participated in our study. The OHIP-14 total score had a mean value of 1.94 (sd 4.39), with a median score of 0 (range 0-29). The oral problems 'oral blisters/aphthae' (25.9%) and 'bad odor/halitosis' (23.3%) were significantly more often reported in CCS than in comparison groups (12% and 12%, respectively). The OHIP-14 score was significantly correlated with the number of self-reported oral health problems (r = .333, p<0.0005) and dental problems (r = .392, p <0.0005). In multivariable analysis, CCS with a shorter time since diagnosis (10-19 years vs. ≥30 years) had a 1.47-fold higher risk of ≥1 oral health problem. CONCLUSION: Though the perceived oral health is relatively good, oral complications following childhood cancer treatment are prevalent in CCS. This underlines that attention to impaired oral health and awareness on this topic is mandatory and regular visits to the dentist should be a part of long-term follow-up care.

Digital polymerase chain reaction to monitor platelet transfusions in cardiac surgery patients.

BACKGROUND AND OBJECTIVES: Corrected count increment (CCI) measurements monitor the effectiveness of platelet transfusions in haemato-oncology, but they usually fail in patients undergoing cardiac surgery. We investigated whether polymerase chain reaction (PCR) of mitochondrial single-nucleotide polymorphisms (SNPs) is able to monitor the survival of transfused platelets in these patients. MATERIALS AND METHODS: Leukocyte-free, platelet-rich plasma was prepared from patients' blood to measure platelet counts based on patient-/donor-specific SNPs by digital PCR after DNA extraction. Platelet counts in samples from patients with severe thrombocytopenia were analysed by both PCR and flow cytometry. Ten patients undergoing cardiac surgery with the use of heart lung machine and without overt bleeding received a single apheresis platelet concentrate because of either dual platelet inhibition during a non-elective intervention or a complex procedure. Blood samples were collected at nine defined intervals (0-120 h) post transfusion. RESULTS: The digital PCR of the seven SNPs reliably quantified levels ≥0.6 G/L platelets, in good agreement with flow cytometry and without interference by other SNPs or by platelet activation. A mean 24-h CCI of 11.8 (range: 5.6-19.8) and a mean 120-h area under the curve (AUC) of 1386 (915-1821) hxG/L were observed for the transfused platelets. The mean AUC of 14,103 (3415-27,305) hxG/L for the patients' endogenous platelets indicates that transfused platelets represented only 11% (5-25) of the total platelet counts during 120 h post transfusion. CONCLUSION: PCR of mitochondrial SNPs offers a tool to assess the survival of platelets from apheresis concentrates in cardiac surgery patients to facilitate the implementation of improved transfusion strategies.

Lipoproteins act as vehicles for lipid antigen delivery and activation of invariant natural killer T cells.

Invariant natural killer T (iNKT) cells act at the interface between lipid metabolism and immunity because of their restriction to lipid antigens presented on CD1d by antigen-presenting cells (APCs). How foreign lipid antigens are delivered to APCs remains elusive. Since lipoproteins routinely bind glycosylceramides structurally similar to lipid antigens, we hypothesized that circulating lipoproteins form complexes with foreign lipid antigens. In this study, we used 2-color fluorescence correlation spectroscopy to show, for the first time to our knowledge, stable complex formation of lipid antigens α-galactosylceramide (αGalCer), isoglobotrihexosylceramide, and OCH, a sphingosine-truncated analog of αGalCer, with VLDL and/or LDL in vitro and in vivo. We demonstrate LDL receptor-mediated (LDLR-mediated) uptake of lipoprotein-αGalCer complexes by APCs, leading to potent complex-mediated activation of iNKT cells in vitro and in vivo. Finally, LDLR-mutant PBMCs of patients with familial hypercholesterolemia showed impaired activation and proliferation of iNKT cells upon stimulation, underscoring the relevance of lipoproteins as a lipid antigen delivery system in humans. Taken together, circulating lipoproteins form complexes with lipid antigens to facilitate their transport and uptake by APCs, leading to enhanced iNKT cell activation. This study thereby reveals a potentially novel mechanism of lipid antigen delivery to APCs and provides further insight into the immunological capacities of circulating lipoproteins.